Staff Reports

	The Place To Be | Joining FORCEs Conference

People and families affected by hereditary breast or ovarian cancer, related cancers or a BRCA mutation are invited to a June conference sponsored by FORCE, or Facing Our Risk of Cancer Empowered. Titled Joining FORCEs Against Hereditary Cancer and held in partnership with Penn Medicine’s Basser Research Center for BRCA, the international conference will take place June 18-20 at the Philadelphia Downtown Marriott Hotel.

Also welcome are patient advocates, researchers and health care providers who treat high-risk patients.

Presentation topics will include genetics, hormone therapy for previvors, treatments, prevention tactics, sexuality issues, fertility, lifestyle choices in survivorship, consequences of menopause, and insurance and legal rights. There will be opportunities for attendees to enroll in clinical trials of treatments for these diseases, including studies funded by Basser, and to consider becoming advocates to improve the lives of people with these hereditary gene mutations or cancers.

The event will feature a “Show and Tell Room” where women contemplating mastectomies can speak with those who have undergone the procedure and surgeons who perform it. Also on the agenda is an After-Hours Spouse Support Group.

	People Report | Jolie Has Preventive Surgery, but Cautions Others with BRCA Mutations to Consider Options

The general registration price is $210, and one-day passes are $125. For more information, visit http://www.facingourrisk.org/getinvolved/ events/annual-conference/index.php.

Actress Angelina Jolie told the world about the continuation of her cancer prevention journey on March 24, when she announced in the New York Times that she’d had her ovaries and fallopian tubes prophylactically removed.

Jolie, who wrote that her BRCA1 gene mutation increases the likelihood that she will develop breast or ovarian cancer by 87 and 50 percent, respectively, announced in a similar editorial two years ago that she had undergone a prophylactic double mastectomy.

In the recent piece, Jolie wrote that she had her ovaries and tubes removed after a cancer scare: A doctor told her that inflammatory markers in her blood, which could indicate the presence of cancer, were high. Although further testing did not reveal any cancer, Jolie decided due to her elevated risk and family history to go forward with the surgery, which put her into menopause.

“I did not do this solely because I carry the BRCA1 gene mutation, and I want other women to hear this,” Jolie wrote. “A positive BRCA test does not mean a leap to surgery…There are other options. Some women take birth control pills or rely on alternative medicines combined with frequent checks…The most important thing is to learn about the options and choose what is right for you personally.”

Valerie Harper, the Emmy Award winning actress who starred in the 1970s television shows “The Mary Tyler Moore Show” and “Rhoda,” was the keynote speaker at CURE’s Extraordinary Healer Awards ceremony, held April 23 in Orlando, Fla., on the eve of the Oncology Nursing Society’s 40th Annual Congress.

Harper, 76, is living with leptomeningeal carcinomatosis, a cancer that affects the meninges, membranes around the brain. The disease is a recurrence of the lung cancer with which Harper was diagnosed in 2009.

The actress, whose mother was a nurse, spoke passionately—and at times humorously&mdash; about the contributions of oncology nurses during the awards ceremony, also helping to present trophies to the winning nurse and two finalists. Those nurses, among many others, were nominated via essay by patients they had treated, or by the patients’ families.

“I have such a deep appreciation for nurses in general,” Harper said, “but especially for you guys and gals delivering what you do. It goes beyond technology and intellect to the heart you have to bring to it, the caring, the softness—a certain candor you have to have to face death. Only three people won the essay (contest), but I know it goes for all of you.”

Will Ferrell raised money for cancer by playing baseball March 12 in an event filmed by HBO that will appear in a “Funny or Die” special.

During the daylong event in Arizona, the comedic actor visited five ballparks to engage in spring training with 10 teams, with the goal of playing every position on the field. Among the teams he played with were the Chicago Cubs, Seattle Mariners, San Francisco Giants, Cincinnati Reds and Los Angeles Dodgers.

	Prevention | 32 Colleges Declared “Free From Tobacco Money”

According to Major League Baseball’s website MLB.com, Ferrell anticipated raising nearly $1 million, partly through the auctioning on the site of memorabilia from his whirlwind baseball tour. Proceeds will benefit Cancer for College, which helps fund college educations for people affected by cancer, and Stand Up to Cancer, an organization that uses celebrity star power to highlight and raise funds for translational cancer research. Major League Baseball was a founding contributor to Stand Up to Cancer.

Preserving the health of young adults is the goal of an effort on college campuses to quell the use of tobacco, spearheaded by Action on Smoking & Health (ASH).

In November 2014, the organization declared 32 colleges and universities to be “Free From Tobacco Money,” having financially divested from tobacco interests “as a way to fight the tobacco epidemic.” According to ASH, this makes it less likely that students will encounter, try and/or become addicted to tobacco products.

“Universities should not profit from tobacco addictions and death,” says Laurent Huber, executive director of ASH. “The money students spend bettering themselves should not be invested in projects that have such a negative impact on the health of students and of people around the world. By divesting from tobacco funds, these schools are doing their part in the fight against tobacco.”

	Integrative Medicine | Considering Group Acupuncture

Schools certified by ASH as tobacco-free include Brown University, Dartmouth College, Emory University Medical School, Harvard University, Johns Hopkins University, Northwestern University, Smith College, Stanford University, Tufts University and the University of Michigan.

Integrative techniques such as yoga and laughter therapy are typically practiced in groups, but does it make sense to administer acupuncture that way? Sure, according to study findings presented in April at the Annual Congress of the Oncology Nursing Society.

The study on group acupuncture found that this lower-cost therapy helped to alleviate pain, neuropathy and digestive problems in people receiving outpatient treatment for cancer.

“Most studies of acupuncture have involved individual settings, but most of the data are with nausea and vomiting and hot flashes, and there are very limited data on neuropathy,” says presenting author Cindy Tofthagen, assistant professor in the College of Nursing at the University of South Florida. “There’s quite a bit (of study on acupuncture) for pain, but this is the first study that evaluates group acupuncture for cancer-related symptoms.”

Acupuncture is less expensive in a group setting because patients need to lie quietly after needles are inserted, allowing the acupuncturist to treat others in the interim. The acupuncturist involved in the study charges $75 for an individual session and $20 per person for a group session, Tofthagen says.

The study included 43 patients who underwent at least four group acupuncture sessions over as many weeks, and completed short assessments of seven cancer-related symptoms. The mean age of participants was 66.4 years, and they were primarily white, non-Hispanic and female.

Symptom improvement was not seen until the fourth treatment, when patients reported significantly less pain and numbness and fewer problems with digestion. While there were no significant improvements in sleep, fatigue or dry mouth, trends toward improvement were seen in all those areas. No reduction of headache was experienced.

“The next step is that we’re (testing) four weeks of acupuncture twice a week, because (the acupuncturist) feels that’s ideal,” Tofthagen says. “Then we’ll evaluate the results at completion and two months later, to see if there are any sustained effects once patients are off the program. If we can show some efficacy over time after the acupuncture is finished, that would be really useful.”

	Legislative Watch | Medicare Begins Covering CT Screening for Lung Cancer

Group acupuncture clinics already exist around the country. An organization known as People’s Organization of Community Acupuncture, online at pocacoop.com, is dedicated to the concept, and may be able to help patients find group acupuncture providers in their local areas.

On Feb. 5, Medicare started covering lung cancer screening with low-dose computed tomography (LDCT) for high-risk individuals, including current and former smokers. The decision to cover the procedure had been announced in November 2014, following months of consternation after the Medicare Evidence Development and Coverage Advisory Committee voted against coverage in late April 2014.

The decision allows Medicare beneficiaries aged 55 to 77 who are current smokers or have quit smoking within the past 15 years to receive LDCT screening once a year. This includes those with a tobacco smoking history of at least 30 pack years — meaning, for instance, at least a pack a day for 30 years, or two packs a day for 15 years. Individuals must have a written order for the test from a health care provider.

The Centers for Medicare & Medicaid Services (CMS) announcement came a little more than a year after the U.S. Preventive Services Task Force (USPSTF) finalized its “B,” or favorable, recommendation for annual lung cancer screenings with LDCT; that recommendation was for adults aged 55 to 80 who had smoked 30 pack years. USPSTF’s recommendation was based on results of the National Lung Screening Trial, which found that patients who received screening had a 15 to 20 percent lower risk of dying from lung cancer; results published in 2013 showed that targeting screening toward those at greatest risk produced the most effective results.

The possibility that Medicare could have opted against paying for the screenings had stirred controversy because, under the Affordable Care Act, commercial insurers are required to pay due to the B recommendation. A decision against coverage would have resulted in free lung cancer screenings being available to some older Americans with heavy smoking histories, but not to others.

“We believe this final decision strikes an appropriate balance between providing access to this important preventive service and ensuring, to the best extent possible, that Medicare beneficiaries receive maximum benefit from a lung cancer screening program,” says Patrick Conway, chief medical officer and deputy administrator for innovation and quality for CMS.

Lung cancer is the leading cause of cancer death in the United States.

It could be a movie. A woman struggles through her cancer journey, facing triumphs and disappointments, often wearing a favorite colorful scarf after she loses her hair to chemotherapy.

When she’s done with her treatment, she passes her scarf to another woman living with cancer, along with a written account of her story. For the woman who receives it, the scarf is a reminder that she’s part of a sisterhood, of sorts.

“The idea started when, as a patient myself, I was sharing scarves and my story, and it was neat to see how it blossomed,” says Lara MacGregor, who was diagnosed with breast cancer while pregnant and now has stage 4 disease. She founded the nonprofit Hope Scarves in Louisville, Ky., three years ago, so far shepherding 2,000 scarves—at no cost&mdash;from woman to woman in every American state and in 12 countries.

Worn either on the head or around the neck, each scarf is dry cleaned upon its return to Hope Scarves, packaged with the stories of all who have worn it, and sent to a new patient seeking support. Scarves are sent to patients with similar cancers, in similar stages, as those who have worn them before. Women may be matched by age, by career — one dancer inheriting a scarf from another – or even, MacGregor says, by the hand of fate.

“We’d given a scarf to someone not knowing it had roses on it, and she was so touched because she had lost her mother and grandmother to cancer, and they all were rose gardeners,” MacGregor recalls.

Patients’ stories are included with the scarves even if they have succumbed to cancer, although recipients aren’t told about their outcomes. “We recognize that we have a unique opportunity to keep their story and encouragement alive through their words,” MacGregor says.

The organization is particularly in need of survivors to share their stories and/or scarves, so that enough will be available to meet the requests made by new patients. Survivors can arrange to do that by filling out an online form.

In addition, anyone is welcome to donate to the organization or invite MacGregor to speak; hospitals can get involved by ordering packages of stories and scarves to keep on hand for their patients.

Finally, scarves can be given as gifts. “It’s a meaningful, inspiring way to support someone you care about,” MacGregor says. “We want to do our small part to change the way people experience cancer, to make it a little less isolating and a bit more beautiful.”

	House Call | What Patients Should Know About Genomic Tests

In addition to the website, Hope Scarves can be contacted by email at info@hopescarves.org, or by phone at (502) 333-9715.

 What should I ask my doctor about genomic tests that could help to diagnose or select a treatment for my cancer?

 “Genomics” appears to be the word of the day. With all the excitement about what our rapidly advancing knowledge of the human genome means for cancer research and treatment, a few questions are currently front and center: Can we rely on the results that patients and doctors get back once they order a genomic-based test? Do we understand all the new information, and can we use it effectively?

Many of these tests — such as those approved by the U.S. Food and Drug Administration (FDA) to determine whether a patient is a candidate for one of the newer targeted therapies &mdash; have been proved through careful study to be reliable and clearly useful. For instance, one FDA-approved test, the Abbott Vysis ALK Break Apart FISH Probe, checks patients with non-small cell lung cancer for the ALK fusion gene. The presence of ALK predicts a response to the targeted drug Xalkori (crizotinib), and the genomic test was approved as a companion to that drug, since a positive test is required before it is prescribed.

Other tests also may be helpful, but have not gone through such a review process. There is no oversight for tests that are done only in a single laboratory, yet doctors and patients routinely rely on them to help chart the course of treatment. These are called “laboratory developed tests,” or LDTs. One such test is Oncotype DX, which looks at a panel of genes to predict whether a women needs more aggressive treatment for her breast cancer, and also evaluates recurrence risk in colon cancer and can help guide prostate cancer treatment. Cologuard, a test that looks at DNA in stool samples to screen for colon cancer, started out as an LDT but was approved by the FDA last year.

As we reported in the winter 2014 issue of CURE, LDTs are now the subject of scrutiny by the FDA, which wants to regulate the tests. The process is still in relatively early stages, and has already resulted in considerable discussion in the scientific and laboratory community. Some say such oversight is necessary to make certain a test is reliable. Others say oversight will stifle innovation, increase costs and threaten to slow down our ability to bring new and important discoveries to patients’ bedsides.

The jury is still out, since the regulations have not been finalized. But you should know that the fact that a genomic test is available doesn’t mean it always will make a difference in your care. You and your doctor should be absolutely comfortable with your decision to use the test, and with the laboratory that conducts it. And, be certain to know whether or not your insurance will cover the cost of the test, which could be substantial.

Don’t hesitate to ask. These are questions your health professional should discuss with you openly and honestly. There is too much riding on the decision to get the test, so understand its implications for your care before it is done.

	Bookshelf | New Beginnings: The Triumphs of 120 Cancer Survivors

Len Lichtenfeld, MD, is deputy chief medical officer of the American Cancer Society. Send House Call questions to editor@curetoday.com.

What’s beautiful about cancer? The strength of the human spirit and the shining faces of those who have survived the disease.

Photographer Bill Aron has captured these aspects of the cancer experience in his book, New Beginnings: The Triumphs of 120 Cancer Survivors. The book includes compelling portraits of survivors and families of all ages and walks of life, along with vignettes about their cancer journeys. Its aim is to convey hope and inspiration.

One featured survivor, 100-year-old Sally Craigen, is quoted as saying: “I am a two-time cancer survivor, but I never stopped enjoying life — dancing and singing with the choir. I’m singing today. People would always say to me, ‘Sally, you don’t act like you have cancer.’ Yes, I’m hurting sometimes, but not enough to stop enjoying life.”

An environmental portrait photographer who has chronicled Jewish communities across the globe, Aron, who holds a Ph.D. in sociology, is himself a 20-year cancer survivor.

“This is a project by and for cancer survivors: their words, my photographs, in collaboration with their ideas and sensibilities,” he writes on his website, billaron.com/ new-beginnings.html. “This is their book.”

The project is a moving look at the positive new insights that can come out of the darkest times, and will resonate with readers regardless of whether they’ve been affected by cancer.

Articles

THE PLACE TO BE / PEOPLE REPORT / PREVENTION / INTEGRATIVE MEDICINE / LEGISLATIVE WATCH / WEB FIND / HOUSE CALL / BOOKSHELF

First Line

The PD-1 inhibitor Opdivo (nivolumab) was granted approval for patients with unresectable or metastatic melanoma following treatment with Yervoy (ipilimumab) or a BRAF inhibitor. The U.S. Food and Drug Administration made the decision three months ahead of its scheduled March 2015 review.

The phase 3 CheckMate-037 trial randomized patients with advanced melanoma to receive Opdivo with chemotherapy---dacarbazine or intravenous carboplatin plus paclitaxel. Opdivo produced an overall response rate of 32 percent compared with 11 percent in patients treated with chemotherapy. In a six-month analysis, 95 percent of responses were ongoing. Fewer serious side effects were reported with Opdivo than with chemotherapy. Opdivo continues to be explored in other cancer types.

Cyramza OK’d for Gastric and Lung Cancers

Cyramza (ramucirumab) is a targeted agent that inhibits a protein involved in angiogenesis, the process of developing blood vessel growth to a tumor. In early November, the FDA approved Cyramza with paclitaxel for patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Seven months earlier, the FDA had approved the drug for patients with the same conditions, but as a single agent.

The phase 3 RAINBOW study of Cyramza and paclitaxel showed a 2.3-month improvement in survival with the combination, and an increase in progression-free survival from 2.9 months to 4.4 months. Because treatment options are limited in this hard-to-treat disease, the survival advantage seen in the Cyramza group was heartening. Neutropenia and high blood pressure were common side effects in the combination arm.

	that had progressed on platinum-based chemotherapy. The anti-angiogenic drug improved overall survival by 1.4 months and progression-free survival by 1.5 months. About a third of patients in the combination arm experienced moderate to severe neutropenia.

Two Drugs Given Green Light in Ovarian Cancer

	The PARP inhibitor Lynparza (olaparib) was approved after a study found it effective in heavily pretreated women with metastatic ovarian cancer who had the BRCA gene mutation. Along with that accelerated approval, the FDA OK’d companion blood test BRACAnalysis CDx, which identifies the presence of BRCA mutations. The approval was based on a 34 percent objective response rate in patients who had received at least three lines of chemotherapy and participated in a phase 2 study. Side effects included nausea, vomiting and diarrhea. In mid-November, Avastin (bevacizumab) was approved in combination with chemotherapy for women with recurrent ovarian cancer that is resistant to regimens containing platinum, becoming the first new treatment for this patient group in more than 15 years. The approval was based on phase 3 study results that showed improved progression-free survival (PFS). Avastin, which blocks a signal that encourages blood vessel growth to the tumor, doubled PFS when compared with chemotherapy alone (6.8 months versus 3.4 months). Median overall survival was also extended by three months. Different regimens of chemotherapy were used during the trial, including Taxol (paclitaxel). A subset of women who received Avastin with Taxol had higher PFS and survival when compared with patients treated with the other chemotherapy combinations. Reported side effects included high blood pressure and hand-foot syndrome.

FDA Approves Blincyto for Acute Lymphoblastic Leukemia 

	Accelerated approval was granted to the immunotherapy Blincyto (blinatumomab), a bispecific antibody, as a treatment for patients who have B-precursor acute lymphoblastic leukemia (ALL) that has recurred or not responded to other therapies. In a phase 2 trial, nearly a third of patients who received Blincyto experienced a complete remission for a median 6.7 months. The Dec. 3 announcement was well ahead of the FDA’s deadline, which provided the treatment to patients much earlier than expected. The most common side effects were fever, headache and swelling in the limbs. Neurological side effects occurred in approximately half of patients. 

Advisory Committee Recommends First Biosimilar for FDA Approval

	In a unanimous vote, an advisory committee to the FDA recommended a biosimilar version of Neupogen (filgrastim) for approval. If given a green light, it would become the first biosimilar approved in the United States. Biosimilars are considered generic versions of expensive targeted therapies, like Neupogen. The supportive care drug stimulates production of infection-fighting neutrophils. A phase 3 trial that compared EP2006 and Neupogen head-to-head in patients with breast cancer who had been treated with chemotherapy showed similar safety and efficacy.

On Dec. 12, the agency also approved Cyramza for the treatment of non-small cell lung cancer (NSCLC). Cyramza was tested in combination with docetaxel for the treatment of metastatic NSCLC

The latest in cancer prevention, diagnosis & treatment.

Pipeline

The annual meetings of the American Society of Hematology (ASH) and the San Antonio Breast Cancer Symposium (SABCS) were held in December, bringing together thousands of cancer researchers, physicians and industry professionals to report on critical issues in cancer treatment, prevention, supportive care and more.

Study Showing PD-1 Inhibitor in Hodgkin Lymphoma Shows Promise

	Immunotherapy, an approach to cancer treatment that has generated a lot of excitement, may work in classical Hodgkin lymphoma. Opdivo (nivolumab), an immunotherapy recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of melanoma, showed promise in patients with classical Hodgkin lymphoma who participated in a small phase 1 trial.

	Most patients in the trial, who had previously progressed after three or more treatments, responded to the immunotherapy, a PD-1 inhibitor. The drug has been granted breakthrough therapy designation for this indication, and is now being investigated in a large phase 2 trial.

	Called a checkpoint inhibitor, Opdivo works by inhibiting the PD-1 receptor that sits on the surface of cancer cells. The receptor, thought to be excessively engaged in the disease, dampens the body’s immune response to the cancer cells.

	After an average follow-up of 40 weeks, 20 of 23 patients in the study demonstrated a response to Opdivo. Four patients experienced a complete response and 16 experienced a partial response. The remaining three patients had stable disease. Median overall survival had not yet been reached. Drug-related side effects occurred in 78 percent of patients, most commonly rash, decreased platelet count, diarrhea and fever.

	“Our data are encouraging for Hodgkin lymphoma patients with relapsed or treatment-resistant disease, and the remarkable response rate seen in this study validates the scientific hypothesis that Hodgkin lymphoma relies heavily on the PD-1 pathway for survival,” said Philippe Armand, lead author and an oncologist at the Dana-Farber Cancer Institute in Boston.

Adcetris Shows Benefit in Hodgkin Lymphoma as Post-Transplant Maintenance Drug 

	New evidence suggests that a specific maintenance drug can make a big difference in helping patients with Hodgkin lymphoma to avoid disease progression after they have received standard treatments.

	Patients with relapsed and difficult-to-treat Hodgkin lymphoma who received high-dose chemotherapy and stem cell transplant, and then about a month later started Adcetris (brentuximab vedotin), had an unprecedented 50 percent higher likelihood of continuing to experience progression- free survival (PFS) at two years. This is particularly meaningful because most patients in this population whose cancers haven’t relapsed two years after transplant are cured.

	“This is the first study in lymphoma to demonstrate that the addition of a maintenance drug after transplant can markedly improve patient outcomes,” said lead author Craig Moskowitz, of Memorial Sloan Kettering Cancer Center. “Given these extremely positive results, we predict that brentuximab vedotin will soon become the standard of care for Hodgkin lymphoma patients who undergo an autologous stem cell transplant.”

	Adcetris is an antibody that targets the CD30 protein on Hodgkin lymphoma cells. The drug was approved by the U.S. Food and Drug Administration in 2011 for the treatment of patients with Hodgkin lymphoma after stem cell transplant failure, or failure of at least two prior multi-agent chemotherapy regimens in patients who are not candidates for transplant. The study presented at ASH considered whether starting Adcetris earlier could prevent such relapses.

	After a median follow-up of two years, researchers found that 65 percent of patients receiving the drug were still experiencing PFS, compared with 45 percent of patients receiving placebo. Overall survival, at a rate of 88 percent at two years, was the same in both arms, although that number was confounded by the fact that 85 percent of patients left the placebo arm upon disease progression to receive Adcetris, and some, following progression, underwent second transplants and were salvaged, Moskowitz said.

	Common side effects were peripheral neuropathy, upper respiratory tract infection, neutropenia, fatigue, cough and fever.

Blincyto Performs in Acute Lymphoblastic Leukemia

	A single cycle of treatment with a targeted drug led to a complete minimal residual disease (MRD) response in most patients with a type of acute lymphoblastic leukemia (ALL), according to the results of a phase 2 study.

	In the study, 80 percent of patients with B-precursor ALL experienced a complete MRD response after a single cycle of treatment with Blincyto (blinatumomab). A few days before the results were presented at ASH, the FDA granted Blincyto accelerated approval as a treatment for patients with Philadelphia chromosome-negative relapsed or refractory B-precursor ALL. According to the FDA’s projected timeline for the drug’s review, the approval came about five months early.

	Blincyto is a bispecific antibody, meaning it can bind to two protein areas and therefore direct cytotoxic T cells to CD19-positive cells. CD19 is a highly specific B-cell marker and is expressed in more than 90 percent of B-cell malignancies.

	“Most patients achieved a complete MRD response within one cycle of treatment,” said Nicola Gokbuget, a hematologic oncologist at Goethe University Hospital in Frankfurt, Germany. “Responses occurred in all subgroups, including older patients and patients with high MRD levels.”

	The most common side effects reported were flu-like symptoms associated with T-cell activation.

CAR T-Cell Therapy CTL019 Shows Long-Term Benefit in Relapsed ALL

	Small and early studies involving CAR T-cell therapy have shown promising results, attracting the attention of patients and the public. A type of CAR T cell termed CTL019 has demonstrated a 92 percent complete response (CR) rate in pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

	“What we really have now that we didn’t have before is longer follow-up. A lot of kids are now a year out. We’re seeing the possibility of longer-term disease control without further treatment, especially without bone marrow transplant, so I am very excited about that,” said lead author Stephan Grupp, director of translational research for the Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia. “I am excited about the prospect of having a pediatric multisite trial to see how well these cells are going to work in broader application.”

	CTL019 is an anti-CD19 chimeric antigen receptor (CAR)-modified T-cell therapy. It involves removing T cells from a patient and reengineering them in a lab so that they will recognize, bind to and destroy cells that express the protein CD19. Once infused into the patient, these engineered T cells multiply, continuing for longer than two years in some patients.

	CTL019 has been granted a breakthrough therapy designation from the U.S. Food and Drug Administration for its potential as a treatment for pediatric and adult patients with relapsed or refractory ALL.

Kyprolis Addition Benefits Patients Experiencing First Myeloma Relapse

A  drug that was approved in 2012 for patients with multiple myeloma that had relapsed after at least two prior therapies has now proven effective as a second-line therapy.

Treatment with Kyprolis (carfilzomib) in combination with Revlimid (lenalidomide) and dexamethasone increased progression-free survival (PFS) by 8.7 months in patients with relapsed multiple myeloma when compared with Revlimid and dexamethasone alone, according to interim results from the ASPIRE phase 3 study. Keith Stewart, dean of research at the Mayo Clinic in Scottsdale, Ariz., presented the results.

“The median progression-free survival with Kyprolis with Revlimid and dexamethasone is unprecedented in first-relapse myeloma at over two years,” said Stewart. Median PFS was 26.3 months in the Kyprolis arm versus 17.6 months in the control arm. In terms of complete response, 31.8 percent of patients in the Kyprolis arm had a complete response compared with 9.3 percent of patients in the control arm, a more than three-fold increase.

The addition of Kyprolis did not increase peripheral neuropathy or other side effects. “Another secondary objective worth noting is that we measured health-related quality of life for patients who participated in the trial,” Stewart said.

“The patients on the three-drug combination reported better global health status that persisted throughout the 18 months of the study that they were on the drug.”

	Ovarian Suppression a Benefit in Certain Estrogen-Positive Breast Cancers

	Hot flashes aside, early menopause can be a good thing for women undergoing treatment for hormone receptor-positive breast cancer.

	Premenopausal women with that cancer who were pushed into menopause via ovarian suppression had a lower risk of disease recurrence if they stayed in medical menopause after receiving chemotherapy and then throughout a course of hormonal therapy, according to results from the phase 3 SOFT trial. The trial compared ovarian suppression plus adjuvant Aromasin (exemestane) or tamoxifen to standard tamoxifen alone. Enrolled were premenopausal women with early hormonepositive breast cancer randomized to either of the two treatments for a period of five years.

	Ovarian suppression did not lower recurrence in the overall study, but in the combination arm, results with Aromasin were most promising, showing a 35 percent reduction in the risk of disease recurrence in the premenopausal women treated with the aromatase inhibitor and ovarian suppression compared with tamoxifen alone.

	Prudence Francis, lead author of the study and head of breast medical oncology at the Peter MacCallum Cancer Centre in Australia, believes the results will change clinical practice when it comes to treating premenopausal women with this condition. “Increasingly, doctors will be talking to them about these results and discussing with them the option of undergoing ovarian function suppression treatment with an aromatase inhibitor as an alternative to tamoxifen,” she said.

	Francis called the SOFT data particularly encouraging for women younger than 35 years, who have a higher risk of recurrence with hormone-sensitive breast cancers. The benefit of adding ovarian suppression to Aromasin was most pronounced in this population.

	Not all women in the SOFT trial benefitted from ovarian suppression, however. Patients were stratified by receipt of chemotherapy, and women in the chemotherapy-naïve cohort did well whether they received tamoxifen alone or ovarian suppression combined with either tamoxifen or Aromasin.

	The next step for the SOFT trial, said Francis, will be to determine how these different treatments will affect overall survival.

Immunotherapy Keytruda Sparks Response in Triple-Negative Breast Cancer

	Keytruda (pembrolizumab), the PD-1 inhibitor that was recently approved as an immunotherapy for advanced melanoma, has demonstrated promising clinical activity in heavily pretreated patients with recurrent metastatic triple-negative breast cancer (TNBC).

	The results from the phase 1b KEYNOTE- 012 trial showed that treatment with Keytruda demonstrated an overall response rate of 18.5 percent in patients with TNBC that expressed PD-L1, a checkpoint in the immune system that prevents T cells from activating to fight cancer. Keytruda interferes with that mechanism, allowing T cells to activate. At the time of the analysis, the median duration of response had not yet been reached.

	The findings from the study were described as the first to demonstrate clinical activity by an immune checkpoint inhibitor in breast cancer, and could pave the way for immunotherapy in the disease.

	“Pembrolizumab showed an acceptable safety and tolerability profile in heavily pretreated PD-L1-positive advanced triple-negative breast cancer patients,” said lead author Rita Nanda, assistant professor of medicine and associate director of the Breast Medical Oncology Program at the University of Chicago. “While 56 percent of patients did experience a therapy-related adverse event, the vast majority of these toxicities were easily managed, well tolerated and did not require treatment discontinuation.” Several follow-up studies in advanced and early-stage breast cancer are planned.

Research updates from the annual meetings of the American Society of Hematology (ASH) and the San Antonio Breast Cancer Symposium (SABCS).

Research Updates from ASH & SABCS

The annual meeting of the European Society for Medical Oncology (ESMO) was held in September, bringing nearly 20,000 cancer researchers, physicians and industry professionals to Madrid, Spain, to discuss the latest data on critical issues in cancer treatment, diagnostics, prevention, supportive care and more. Here we offer a sampling of the studies that were presented.

Perjeta Shows Dramatic Survival Boost in Patients with HER2-Positive Breast Cancer

The development of Herceptin (trastuzumab) was a game changer for people with HER2- positive breast cancer. Given with or after chemotherapy, Herceptin, approved by the U.S. Food and Drug Administration (FDA) in 1998, reduces recurrence rates by half in specific types of early HER2-positive breast cancer and by one-third in metastatic HER2- positive breast cancer.

Now, a study has demonstrated that adding a second monoclonal antibody—Perjeta (pertuzumab)&mdash;to Herceptin and chemotherapy can further reduce the risk of death by about a third in patients with advanced HER2-positive breast cancer.

The information was reported in updated results from the phase 3 CLEOPATRA study. After a four-year follow- up, the triple combination extended survival by nearly 16 months over the standard treatment of Herceptin and chemotherapy (56.5 months compared with 40.8 months, respectively).

“We haven’t ever seen that in any other trial of metastatic breast cancer,” said one of CLEOPATRA’s lead researchers, medical oncologist Sandra Swain. Progression-free survival also improved with the addition of Perjeta.

Perjeta was approved in 2012 for patients with metastatic HER2-positive breast cancer, and was later granted accelerated approval for early-stage cancer before surgery. Reported side effects included rash, diarrhea and low blood counts.

“Based upon the study results, I would recommend personally that all patients have an opportunity to get dual-antibody therapy—pertuzumab and trastuzumab,” Swain concluded.

Nivolumab Beats Chemo as Second-Line Treatment for Advanced Melanoma

An investigational immunotherapy may be more effective than chemotherapy in patients with metastatic melanoma, according to the results of a phase 3 study.

Nivolumab was found to delay tumor growth when compared with chemotherapy in patients with metastatic melanoma. The immune checkpoint inhibitor antibody targets the PD-1 receptor of certain T lymphocytes, thus blocking a pathway that cancer cells use to elude the body’s immune system.

The study presented at ESMO included more than 400 participants whose disease had progressed after treatment with Yervoy (ipilimumab), an immunotherapy already approved for this group of patients by the FDA. If their tumors expressed a BRAF mutation, trial participants were treated with a BRAF inhibitor in addition to nivolumab.

Researchers found that patients treated with nivolumab had a faster tumor response than those treated with chemotherapy, as well as a longer response. Responses with nivolumab were seen regardless of PD-L1 expression status before treatment, BRAF mutation status or whether the patient had responded to other anti-CTLA-4 therapies, such as Yervoy. However, more patients with PD-L1-positive tumors responded than did those with PD-L1-negative tumors. Nivolumab also generated fewer moderate or serious side effects than chemotherapy (9 percent compared with 31 percent).

The drug has been granted a priority review by the FDA, with an approval decision expected in early 2015.

Two Approved Treatment Strategies Generate Similar Results in Specific Patients Who Have Metastatic Colorectal Cancer

If a RAS mutation is present in a colorectal tumor, targeted therapy that inhibits a specific cellular growth pathway, the epidermal growth factor receptor (EGFR), is not helpful, researchers have found. But in patients who don’t have a RAS mutation, which EGFR inhibitor works best?

A pair of studies examined the impact of two therapies in previously untreated patients with colorectal tumors that did not have a RAS mutation, and found that they were similarly effective.

One of the treatments, the antiangiogenic drug Avastin (bevacizumab), blocks blood growth to the tumor. The other, Erbitux (cetixumab), blocks EGFR.

In addition to determining whether either therapy provided more benefit over the other for patients without a RAS mutation, the studies were designed to tease out other factors that could help guide individual treatment decisions. Treatment choices in colorectal cancer can involve a number of factors, including the molecular biology of the tumor and biomarkers such as mutations to the RAS family of proteins, as well as patient characteristics such as age, comorbidities and goals for treatment.

Overall, researchers concluded that there was no difference in survival or disease progression between the two therapies, and that either is appropriate for patients in this group. The most promising news was that overall survival in both studies reached more than 30 months, the longest reported in first-line treatment for patients with newly diagnosed metastatic colorectal cancer.

The study results demonstrate that all patients with metastatic colorectal cancer should be tested for RAS mutations, researchers concluded. But the findings also make it clear that useful biomarkers beyond RAS mutations need to be found in order to determine the best treatments for patients.

The annual meeting of the European Society for Medical Oncology (ESMO) was held in September to discuss the latest data on critical issues in cancer treatment, diagnostics, prevention, supportive care and more.

Updates from the European Society for Medical Oncology

Prostate Cancer Drug Xtandi Gains New Indication

Xtandi (enzalutamide), a hormonal treatment approved in 2012 for use after chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC), now has the green light for use before chemotherapy in men with the same condition. On Sept. 10, the U.S. Food and Drug Administration (FDA) concluded a priority review by expanding the drug’s use based on data from the phase 3 PREVAIL trial. The study showed that Xtandi improved overall survival by 29 percent and progression-free survival, which was based on imaging scans, by 81 percent compared with placebo in men who had not received prior chemotherapy.

“In the PREVAIL trial, the median time to initiating chemotherapy was delayed by 17 months with enzalutamide treatment as compared to placebo, so the result is a meaningful period of time during which men have their disease controlled without the need for chemotherapy,” said the trial’s lead investigator, Tomasz M. Beer, deputy director of the Knight Cancer Institute and professor of medicine at Oregon Health & Science University.

With the addition of Xtandi, the median time before beginning chemotherapy was prolonged from 10.8 months to 28 months. A decline in prostate-specific antigen of greater than 90 percent was detected in 46.8 percent of patients treated with Xtandi compared with 1.2 percent for placebo. Median overall survival was 32.4 months with Xtandi versus 30.2 months with placebo.

The most common side effects with Xtandi versus placebo were fatigue, back pain and constipation.

A drug recently approved for the treatment of three distinct blood cancer types could eventually be OK’d as therapy for a fourth group—patients with Waldenström’s macroglobulinemia (WM). As of Oct. 22, the FDA was reviewing Imbruvica (ibrutinib) as a potential treatment for WM. The drug is already approved for the second-line treatment of mantle cell lymphoma and chronic lymphocytic leukemia (CLL), and also for a subtype of CLL identified as having a chromosomal abnormality called a 17p deletion. If granted the new indication, Imbruvica would become the first treatment approved specifically for use in WM, a rare, slow-growing, incurable type of B-cell lymphoma.

Data reported at the 2013 annual meeting of the American Society for Hematology showed that Imbruvica rapidly reduced levels of serum immunoglobulin M, an antibody produced by B cells, and improved hematocrit levels in patients with relapsed or refractory WM. However, patients who harbored a specific mutation present in about 30 percent of patients with WM were less likely to respond to the agent.

Lenvatinib Could Be an Option in Thyroid Cancer

The FDA granted a priority review Oct. 14 to the targeted drug lenvatinib as a potential treatment for patients with progressive, radioactive iodine-refractory differentiated thyroid cancer. The FDA expects to make a decision by April 14, 2015.

There were no effective treatment options for patients with this condition until November 2013, when the FDA approved Nexavar (sorafenib). Like Nexavar, lenvatinib, an oral drug, is an anti-angiogenic agent that blocks blood vessel growth to the tumor.

The new drug application for lenvatinib was based on findings from the phase 3 SELECT trial that were presented at the 2014 annual meeting of the American Society of Clinical Oncology. In the study, the risk of disease progression was reduced by 79 percent in patients treated with lenvatinib compared with placebo. The median progression-free survival (PFS) with lenvatinib was 18.3 months versus 3.6 months with placebo.

The median PFS with lenvatinib following treatment with a prior anti-angiogenic therapy was 15.1 months. Median overall survival numbers were not yet available.

Side effects included hypertension, diarrhea, decreased appetite, weight loss and nausea.

Expedited Review for Colorectal Cancer Drug 

Patients with metastatic colorectal cancer that has progressed on other therapies moved closer to gaining a new treatment option on Oct. 20, when the FDA granted fasttrack designation to the drug tipiracil (TAS-102).

The request for FDA approval is based on promising findings from the phase 3 RECOURSE study. In the study, patients treated with tipiracil had an overall survival of 7.1 months compared with 5.3 months for those taking placebo. Median progression-free survival was 2 months in the investigational arm versus 1.7 months with placebo. The drug worked better in patients who did not have a KRAS mutation.

Prostate cancer drug Xtandi, as well as the blood cancer drug Imbruvica, may help additional patients with these cancers. 

FDA Approves New Uses for Existing Cancer Treatments

The American Society of Clinical Oncology (ASCO) hosted its 50th annual meeting in Chicago from May 30 to June 3, bringing together more than 34,600 cancer researchers, physicians, industry professionals, advocates and survivors to report on advances in cancer screening, diagnosis, treatment and prevention. For more coverage of the conference, visit 

Hormone therapy is a standard treatment for men with advanced prostate cancer, but when the cancer progresses, chemotherapy is often used. Researchers questioned whether chemotherapy would improve survival if it was given earlier, during hormone therapy and before the cancer becomes resistant. The investigators found that combining the chemotherapy drug docetaxel early in treatment with hormone therapy improved survival by 10 months in patients with newly diagnosed, stage 4 hormone-sensitive prostate cancer.

The trial studied 790 men, with about two-thirds having extensive metastases. Median overall survival improved from 44 months to 57.6 months, and men with extensive metastases saw an improvement from 32.2 months to 49.2 months—a 17-month improvement. Overall survival in men with less extensive metastases is not yet known, but researchers are continuing to follow the group to determine whether there is a benefit from the combination.

The addition of chemotherapy resulted in one treatment-related death out of 397 participants. Participants also reported neuropathy as well as low white blood cell counts and fever, which could result in increased infection risk.

“The benefit in patients with a high volume of metastases is clear and justifies the treatment burden,” said Christopher Sweeney, the study’s lead author and an oncologist at Dana-Farber Cancer Institute in Boston. “Longer follow-up is required for patients with low volume metastatic disease.”

Michael Morris, an oncologist at Memorial Sloan Kettering Cancer Center in New York, provided commentary after the presentation and noted the large jump in survival is practically unheard of in this patient population. “If you look at every drug that prolongs survival in castration-resistant disease, none even come close in terms of survival prolongation to 17 months. Our best therapies in metastatic castration-resistant disease are less than a third of that for the high-volume patients in [the] ECOG3805 [study],” he said, noting that the combination uses a generic, older chemotherapy at a fraction of the cost of newer therapies. 

After a long period with little progress, a number of new therapies for treating melanoma have been highlighted at recent ASCO annual meetings, and this year was no exception. Hoping to build on the successful introduction of the immunotherapy drug Yervoy (ipilimumab), researchers investigated whether it would be effective in treating patients with earlier-stage disease who remained at high risk of recurrence after surgery. Yervoy was approved in 2011 for treating inoperable, late-stage melanoma.

In the phase 3 study, 951 participants whose stage 3 melanoma had been surgically treated were randomized to receive Yervoy or a placebo. Alexander Eggermont, the study’s lead author, reported that after 2.7 years, Yervoy was shown to reduce the risk of recurrence by about 25 percent compared with placebo. However, participants experienced considerable side effects, including inflammation of the colon, thyroid and pituitary gland, as well as skin rash. In fact, more than half (52 percent) of participants discontinued the treatment because of side effect severity, and five treatment-related deaths occurred.

Two other immune-checkpoint inhibitor drugs—pembrolizumab and nivolumab&mdash;showed success in early phase 1 trials. In a study of 411 participants with advanced melanoma, pembrolizumab proved effective in participants who had received multiple prior therapies, including Yervoy, as well as those whose metastatic disease was newly diagnosed. Overall, 34 percent of participants experienced tumor response, with an estimated survival rate of 69 percent at one year. Twelve percent of participants experienced serious treatmentrelated side effects, with 4 percent dropping out because of the severity of the side effects. Pembrolizumab, an antibody that blocks a pathway on T-cells, previously received a breakthrough therapy designation for treating inoperable, late-stage illness, and was granted a priority review under the FDA’s accelerated approval program in May.

In a third study, researchers investigated whether combining the antibody drug nivolumab with Yervoy would improve long-term survival for patients with advanced melanoma. Results showed that 41 percent of the 53 participants responded to the treatment, with 17 percent experiencing complete remissions. The median survival rate was about 40 months, and side effects were considered manageable and reversible. 

While non-small cell lung cancer (NSCLC) is considered a hard-to-treat cancer, three studies presented at ASCO may help researchers decide on the best treatment for individual patients, as well as uncovering possible new approaches for squamous cell lung cancer, a type of NSCLC that hasn’t benefited from recent advances in targeted therapy.

Patients whose cancer has progressed or relapsed after initial therapy typically experience a median survival of about seven to nine months. In the REVEL study, patients who received ramucirumab with standard docetaxel lived a median of 10.5 months compared with patients receiving docetaxel alone (9.1 months). Researchers noted that while the survival difference is incremental, this is the first trial in a decade that has shown a survival advantage in second-line therapy for NSCLC.

In one of the largest studies ever conducted in squamous cell lung cancer, necitumumab, an investigational agent that targets the EGFR mutation in certain lung cancers, also improved survival, albeit modestly. The drug was tested in 1,093 participants who had stage 4 squamous cell NSCLC. The patients who received necitumumab with standard chemotherapy experienced longer median survival (11.5 months compared with 9.9 months with standard chemotherapy), as well as longer progression-free survival. Because there are few options for this type of NSCLC, necitumumab is expected to be under Food and Drug Administration review for approval by the end of the year.

Preventing early menopause and preserving fertility are common concerns among women undergoing chemotherapy for breast cancer. A phase 3 trial found that adding goserelin, a hormone-suppressing drug, to standard chemotherapy could help prevent early menopause and preserve fertility in early-stage, hormone receptor-negative breast cancer patients.

In the study, premenopausal women who were given goserelin with a cyclophosphamidecontaining chemotherapy were less likely to have ovarian failure than women who received chemotherapy alone. The addition of goserelin also seemed to improve the chances of a successful pregnancy. Goserelin is a luteinizing hormonereleasing hormone (LHRH), which suppresses ovarian function for a short time. Researchers hypothesize that this action protects the follicles, small structures inside the ovaries in which eggs form, from chemotherapy damage. Side effects, such as hot flashes, were similar to those of menopause.

“Now we should offer all premenopausal women with ER-negative breast cancer about to embark on chemotherapy the option to take the goserelin to prevent sudden menopause from the chemotherapy and all the symptoms that come with it,” says senior study author Kathy Albain, a professor at Loyola Medicine and 

A still inconclusive finding in the study was that women who received goserelin were also 50 percent more likely to survive without disease recurrence four years after treatment compared with those who did not receive goserelin. “This is an intriguing and unexpected finding, and possibly is due to interactions of the shot with the breast cancer cells in some way,” Albain says. “For example, breast cancer cells can have LHRH receptors on the surface, which is the target for goserelin. There are other theories. The good news about these findings is that it is safe, and if anything, breast cancer survival is better.”

Thyroid cancer is considered highly curable, but for 5 to 15 percent of patients, the standard treatments of surgery and radioactive iodine (RAI) therapy aren’t enough to keep the disease from advancing. Researchers announced results of a phase 3 trial of the oral kinase inhibitor lenvatinib that could provide another treatment option similar to Nexavar (sorafenib), which was approved by the Food and Drug Administration (FDA) for treatment-resistant tumors in 2013.

In the study, 392 participants whose disease had progressed within 13 months of previous treatment were randomized to receive lenvatinib or a placebo. Researcher Martin Schlumberger, professor of oncology at the University Paris Sud in Paris, France, said 65 percent of participants who took lenvatinib experienced tumor reduction, compared with 2 percent who received placebo. Moreover, the time to disease progression was more than 18 months for participants on the lenvatinib arm, compared with almost four months for those on placebo. However, 97 participants who took lenvatinib experienced some adverse events, primarily high blood pressure, diarrhea, decreased appetite, fatigue and nausea. 

Adjuvant therapies are given after primary treatment, usually surgery, to reduce the risk of cancer recurrence in many patients. Findings from two large-scale studies on adjuvant therapies in breast cancer were presented at ASCO, signifying the importance of these treatments.

Early findings were released in a joint analysis of two phase 3 studies (TEXT and SOFT), which found Aromasin (exemestane) slightly more effective than tamoxifen when given with ovarian function suppression in preventing recurrences in premenopausal patients with hormone receptor-positive breast cancer. Researchers found about a 4 percent difference in recurrence risk over four years. However, investigators are awaiting final data from the tamoxifen-only arm, which are anticipated to be presented at the San Antonio Breast Cancer Symposium in December.

The second phase 3 study (ALLTO) examined adding Tykerb (lapatinib) to or after adjuvant Herceptin (trastuzumab) for patients with early-stage, HER2-positive breast cancer. These multidrug regimens did not prove more effective than the standard treatment of Herceptin alone. Researchers found no statistically significant difference in treatments after four and a half years.

Cancer researchers and clinicians gathered in Chicago to discuss advances in cancer research.

Updates from the American Society of Clinical Oncology's Annual Meeting

The American Society of Clinical Oncology (ASCO) hosted its annual meeting in Chicago from May 31 to June 4, attracting more than 32,000 cancer researchers, physicians, industry professionals, advocates and survivors to report on advances in cancer care, screening, treatment and prevention. For more coverage of the conference, visit 

The promise of training the body to recognize and kill cancer cells—without the side effects of traditional cancer therapies&mdash;has intrigued researchers for years. While a handful of immunotherapies are approved, a new class of drugs zero in on a protein called PD-1. This protein is present on the surface of activated T cells, immune cells that would ideally attack cancer cells. However, some cancer cells express PD-ligand 1 (PD-L1), which binds to PD-1, switching off the T cell and rendering cancer cells invisible to the immune system.

Several early-stage studies have given researchers confidence to move forward on certain PD-1 inhibitors, calling the drug class a "game changer" in melanoma. In a phase 1 study, participants who had been treated for advanced disease received the PD-1 inhibitor nivolumab with Yervoy (ipilimumab). While phase 1 studies look for safety issues and optimal dosing, this study found almost a third of patients had an 80 percent or greater reduction in tumor size. A phase 3 study in advanced melanoma is scheduled to begin this summer and might be the basis for approval.

A second PD-1 inhibitor, lambrolizumab, also showed impressive results with a 52 percent overall response rate in one cohort of patients. Another drug, MPDL3280A, binds to the cancer cells’ PD-L1, which prevents it from attaching to the T cell. More than a third of patients with incurable cancers, including melanoma, that expressed PD-L1 had a response to the drug as opposed to 13 percent of PD-L1-negative tumors. Further studies are planned to verify results.

"This work is going to change the state of the care of our patients with melanoma," said Walter J. Urba, director of cancer research at the Robert W. Franz Cancer Research Center in Portland, Ore., noting that treatment for melanoma has had many recent advances.

Because these drugs affect the immune system, researchers are concerned with inflammation-related or autoimmune side effects. However, they are excited about the efficacy and low toxicity of these drugs, which will need to be confirmed in larger trials. 

Updates from the annual meeting of the American Society of Clinical Oncology.

Staff Reports

First Line

Pipeline

Research Updates from ASH & SABCS

Updates from the European Society for Medical Oncology

FDA Approves New Uses for Existing Cancer Treatments

Updates from the American Society of Clinical Oncology's Annual Meeting

ASCO Updates

Research Updates

ASCO Updates

Management Strategies for Cancer Therapy Side Effects

Latest News