After a dry spell, metastatic prostate cancer sees dramatic improvement with new therapies

BY ELIZABETH WHITTINGTON | FEBRUARY 1, 2012

Prostate cancer has seen its share of progress over the past few years, including several new drugs that have been approved for patients with metastatic disease. On Tuesday, results of two clinical studies were announced that foreshadow additional therapies that will help further extend survival and improve quality of life.

While prostate cancer is one of the most common cancers, it has a 99 percent five-year survival rate, with most patients diagnosed at an early stage. But for more than 28,000 men this year, prostate cancer will be fatal. For many of these patients, those with metastatic prostate cancer to the bones or men whose cancer doesn't respond to standard hormonal treatment, Alpharadin and MDV3100 could be very useful.

Alpharadin (radium-223) is an intravenous drug that uses alpha particles (a type of ionizing radiation) to kill cancer cells. MDV3100, a new form of hormone therapy, is a pill that works by preventing the tumor cells from using testosterone that can spur cancer growth. The two drugs work very differently and both improve survival, which led some researchers to suggest that combining these agents with other therapies could produce a synergistic response.

In the Alpharadin trial (called ALSYMPCA), 922 prostate cancer patients with bone metastases were randomized two to one to Alpharadin or placebo, with all patients receiving best supportive care. Because the most common site of prostate cancer metastasis is typically bone tissue, targeting a drug to delay or attack cancer at the bone seems like a smart idea. That's what Alpharadin does--it targets the cancer cells that have invaded the bone tissue. It's not a cure, but it did prolong survival by 30 percent (14 months versus 11.2 months) and delayed the time to a patient's first skeletal-related event, such as a spinal cord compression or bone fracture by a median of 5.2 months (13.6 months versus 8.4 months). The side effects of the drug are surprisingly minimal--a slight increase in neutropenia and diarrhea.

The AFFIRM trial, which involved MDV3100, also randomized patients two to one with the experimental treatment versus placebo. The trial included 1,199 patients with metastatic prostate cancer that had progressed after treatment with docetaxel and other hormonal therapies.

The drug increased survival by a median of 4.8 months over placebo (18.4 months versus 13.6 months). Howard Scher, MD, chief of genitourinary oncology at Memorial Sloan-Kettering Cancer Center in New York and co-lead investigator of the AFFIRM study, also noted that more patients treated with the drug experienced tumor shrinkage and more than a 50 percent decline in PSA levels. The drug also delayed cancer growth by five months. Side effects, which included diarrhea, fatigue and hot flashes, were well-tolerated and had similar rates of toxicity to the placebo arm.

Nicholas Vogelzang, MD, chair and medical director of the Developmental Therapeutics Committee of US Oncology, who moderated the press briefing on Tuesday, called the results unprecedented. "This will definitely change the way we take care of patients every day in the office."

He may not have to wait long. MDV3100 has been submitted to the Food and Drug Administration. And both MDV3100 and Alpharadin have been granted fast-track status, which means they will likely have a quicker-than-usual review by the agency.

• Zytiga approved for metastatic prostate cancer

A 'gutsy' phase 3 clinical trial in colorectal cancer

BY ELIZABETH WHITTINGTON | JANUARY 30, 2012

I'm finalizing one of our stories from the ASCO Gastrointestinal Cancers Symposium this week - that of regorafenib, a multi-targeted drug that showed a slight median survival advantage in metastatic colorectal cancer patients who had progressed on three or more lines of therapy. Regorafenib targets several different cancer growth pathways, which makes it unique and could explain why it works against tumors that have progressed on so many other therapies.

And while the phase 1 data wasn't a slam dunk, it was decided that it would skip phase 2 and move directly to phase 3 -- a move one physician called "gutsy." But it worked and will most likely be approved -- much sooner than if the drug had traveled the traditional route.

Another study, which followed the regorafenib presentation, was that of brivanib, another experimental targeted agent for metastatic colorectal cancer. This drug also showed positive results in phase 1 and was moved directly to phase 3. However, unlike regorafenib, the study turned out to be negative. It delayed cancer growth, but survival did not significantly improve.

Both were considered promising drugs and had solid study designs, but one worked and one didn't.

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A call for more pancreatic cancer research

BY ELIZABETH WHITTINGTON | JANUARY 25, 2012

This past weekend I attended the ASCO Gastrointestinal Cancers Symposium in San Francisco. In addition to learning about advancements (and setbacks) and talking with researchers on colorectal, pancreatic, liver and gastric cancers, I also had the chance to talk to a few advocates, including Julie Fleshman, president of the Pancreatic Cancer Action Network, and Anitra Talley, director of patient services and medical relations.

As we were talking about the studies presented on pancreatic cancer that first day, Julie mentioned that pancreatic cancer is still one of the hardest to treat cancers, and more research dollars and studies are desperately needed. She then laid out their goal for 2020 -- to double the five-year survival rate of pancreatic cancer from 6 percent to 12 percent. While 12 percent may not seem an ambitious goal to some, those in the pancreatic cancer community know what a huge leap this would be. It's an admirable goal, especially when the rate of pancreatic cancer is increasing, but not survival.

Included in their strategy is to increase the number of patients in clinical trials, which is probably around 3-5 percent. To do that, PanCan has designated January as National Pancreatic Cancer Clinical Trials Awareness Month. By increasing the number of patients in trials, research can move forward at a faster pace.

While PanCan has helped patients find clinical trials before, they really wanted to focus on this aspect of research. Before January, PanCan's record of calls and emails asking about clinical trials was 154.

"By the second week of January, we had 331, doubling our highest week ever," Julie said. I'll be interested in seeing how many inquiries they received the second half of the month.

I also learned that PanCan, as well as the Lustgarten Foundation, are working with the American Association for Cancer Research (AACR) on its first pancreatic cancer-specific meeting (Progress and Challenges) this summer, bringing researchers and clinicians together to devote three days to pancreatic cancer. PanCan has also brought in more than $4 million for research grants and awards to young investigators to study the disease.

With an approach that focuses on both patients and researchers, I'm hoping that at my next GI meeting, I'll hear more good news.

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The big news from the American Society of Hematology

BY ELIZABETH WHITTINGTON | JANUARY 2, 2012

There were several big studies that were presented at the 2011 annual meeting of the American Society of Hematology, including many early phase studies in lymphoma, leukemia and myeloma.

One of the surprising studies that came out included a phase 3 study of a drug that was withdrawn from the market last year called Mylotarg. It appears that it may have a second life after researchers tweaked the dose for older patients with acute myeloid leukemia.

Mylotarg, also known as gemtuzumab ozogamicin, was approved back in 2000 for relapsed AML, but was withdrawn when follow-up studies showed the drug did not improve response rates and also increased the risk of a rare, but life-threatening liver complication called VOD (veno-occlusive liver disease).

A French group tested the drug in a phase 3 trial using a modified dosing regimen that was easier on patients, which reduced side effects and significantly improved survival. Newly diagnosed patients aged 50 to 70 years who received standard chemotherapy with 3 mg/m2 three times a week lived longer than patients on chemotherapy alone (19.2 months versus 34 months).

"With the lower dose, we have less toxicity ... and we have more efficacy," says Sylvie Castaigne, MD, lead investigator of the ALFA study. She said this recent study included fewer deaths from VOD than in the past studies, but that patients also experienced low platelet counts, however that side effect was manageable.

Several ongoing trials with Mylotarg may show the drug still has a place in AML treatment. The drug's maker, Pfizer, is waiting for additional study results before determining whether to resubmit the drug to the FDA for approval.

"At this point, we are trying to better understand the data out there in hopes that they indeed look as good as we would like them to look," says Mark Shapiro, MD, PhD, a senior director of global medical affairs with the drug company. "Pfizer is definitely interested, the issue is what can we do with this data."

Because the drug has been withdrawn, it is typically not available to most patients. However, it is still being studied in clinical trials. Additionally, there are other studies looking at a second-generation drug called inotuzumab ozogamicin.

You can read more from ASH from Dr. Anas Younes (Studies highlight progress in lymphoma, pose more questions) and other stories on lymphoma, myeloma and leukemia in our News section.

• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• Studies highlight progress in lymphoma, pose more questions
• Drug approved specifically for treating myelofibrosis

Afinitor impresses in advanced hormone-positive breast cancers

BY ELIZABETH WHITTINGTON | DECEMBER 8, 2011

One of the most highly anticipated presentations at this year's SABCS is BOLERO-2 (Breast Cancer Trials of Oral Everolimus-2), a phase 3 study examining whether adding Afinitor (everolimus) to Aromasin (exemestane) in postmenopausal women with advanced estrogen-positive breast cancer would delay disease progression.

The study followed 724 patients with progressing breast cancer who have responded to previous hormone therapy for their cancer.

The BOLERO-2 trial was halted in February when it became apparent the Afinitor combination was better than Aromasin alone, much sooner than expected, said investigator Gabriel N. Hortobagyi, MD, director of the Breast Cancer Research Program at the University of Texas M.D. Anderson Cancer Center in Houston. Preliminary data were announced at a European meeting in September showing that with the addition of Afinitor, progression-free survival (PFS) improved from 2.8 months to 6.9 months.

Researchers announced updated results at the San Antonio Breast Cancer Symposium, and after a year follow-up PFS had improved from 3.2 months in the Aromasin arm to 7.4 months in the Aromasin and Afinitor arm, an improvement of about 57 percent. Response rates also doubled from 25.5 to 50.5 percent, which included complete and partial responses, as well as stable disease lasting at least six months. Side effects in the combination arm included oral mucositis, rash, diarrhea and fatigue.

Data also suggest a survival benefit, but researchers were quick to caution that survival results arenot expected for another year. Hortobagyi says it may be another year before survival data is available.

Afinitor inhibits mTOR, a protein that helps regulate the growth of cancer cells and blood vessels. Aromasin is a commonly used drug in hormone-positive cancers that inhibits the enzyme aromatase, blocking its conversion to estrogen, the hormone that drives tumor growth in certain breast cancers. It's believed that some cancers that are resistant to hormonal therapy have an over-activation of the mTOR pathway. By using an aromatase inhibitor in combination with Afinitor, researchers hope to overcome that resistance.

At last year's symposium, results of a study suggested that women with metastatic disease taking Afinitor and tamoxifen live longer. Two other BOLERO studies are looking at whether Afinitor benefits women when combined with Herceptin (trastuzumab) and Taxol (paclitaxel) or vinorelbine. Afinitor is currently approved to treat advanced kidney cancer.

Novartis, the drug's maker, is expected to submit Afinitor to the FDA for use in advanced breast cancer within the next few weeks in light of the positive results.

You can read about the study in the New England Journal of Medicine.

• For the Cure to a broken heart
• An update on the Cancer Genome Atlas for breast cancer
• Video blog: Test could spare some DCIS patients from radiation
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Blogroll for San Antonio's breast cancer meeting

BY ELIZABETH WHITTINGTON | DECEMBER 7, 2011

It's hard to follow all the great stories and commentaries coming out of SABCS while also taking in the sessions. I started keeping up with a list of bloggers I wanted to go back and read for later and thought I would share it with you, too. Some are advocates, some are survivors, some are doctors, but all have the same goal of sharing what they learn here.

Kathi Apostolidis
Alamo Breast Cancer Foundation
Breast cancer and patient rights advocate blogging for the Alamo Breast Cancer Foundation

Sally Church
Pharma Strategy Blog
More scientific, but her joy in learning about what drives drug resistance and new therapies is infectious

Karuna Jaggar
Breast Cancer Action
Karuna is the executive director of Breast Cancer Action

Jody Schoger
Women with Cancer
http://womenwcancer.blogspot.com/
Breast cancer survivor and advocate, health blogger, her husband is a melanoma survivor

Dr. Debu Tripathy
Dr. Debu's CURE blog
Editor-in-chief at CURE, Co-Leader of the Women's Cancer Program at Norris Comprehensive Cancer Center and Professor of Medicine at the Keck School of Medicine at the University of Southern California (what a mouthful!)

Let me know if you're blogging from San Antonio (or remotely!) and I'll include your blog.

• For the Cure to a broken heart
• An update on the Cancer Genome Atlas for breast cancer
• Video blog: Test could spare some DCIS patients from radiation
• Video blog: HER2-targeted agents
• Video blog: Complications with brachytherapy in breast cancer

Breast Cancer and the Environment Report offers research roadmap

BY ELIZABETH WHITTINGTON | DECEMBER 7, 2011

The release of the Institute of Medicine's Breast Cancer and the Environment: A Life Course Approach report has generated quite a bit of interest. Many are expecting information on BPA, pollution and cosmetics; what we get is that there needs to be more research.

The committee defined "environmental" as most non-hereditary causes of cancer. Many of the environment factors it discusses that are preventable are those that can be changed by lifestyle. In addition to exercising more, drinking less alcohol and avoiding tobacco use, the report did mention some other notable topics:

 Forego hormone therapy replacement – when the WHI study results were published in 2002 linking HRT to breast cancer, many women taking HRT for menopausal symptoms stopped taking the drug, and the rate of breast cancer significantly dropped.

 Reduce radiation exposure – this doesn't mean not going through the X-ray machine at the airport when you travel for the holidays nor does it mean cutting back on screening mammograms. But if you don't need a full body CT scan every year, it's probably not a good idea to get one.

Some things the report didn't include as environmental carcinogens are probably noteworthy in itself, such as cosmetics and BPA (Bisphenol A).

Instead the report outlined future methods to studying environmental causes, suggesting that the way most studies are conducted isn't adequate. This we know because of the back-and-forth, contradictory studies on everything from cell phones to supplements. The committee recommends looking into exposures over the course of a lifetime (hence the report's title), including in utero, while also taking into account the combination and mixture of chemicals, interplay between genetics and environmental toxins, and length of exposure and age when exposed. These are difficult topics to study and will take a lot of time and money before we have anything meaningful.

"We know that breast cancer is influenced by hormones, and estrogen exposure is a risk factor," said Irva Hertz-Picciotto, PhD, chair of the committee. "A number of compounds are active estrogenically - those are opportunities for potentially reducing risk. BPA is one of those compounds," and therefore, she says, deserves more research attention. Currently, there is little to no epidemiological research on BPA and cancer risk. Other possible breast carcinogens that need more research are benzene and night-shift work. Some expressed disappointment that the report didn't turn up more definitive answers and prevention strategies.

"What we found was that the evidence base wasn't there to say these (other factors) contribute to breast cancer. I think we were all disappointed to not be able to recommend more," said Herz-Picciotto during the presentation's question-and-answer Wednesday afternoon.

The report was funded by Susan G. Komen for the Cure. If you'd like to download the free pdf of the report, go to iom.edu/breastcancerenvironment.

• For the Cure to a broken heart
• An update on the Cancer Genome Atlas for breast cancer
• Video blog: Test could spare some DCIS patients from radiation
• Video blog: HER2-targeted agents
• Video blog: Complications with brachytherapy in breast cancer

Saving your oocytes

BY ELIZABETH WHITTINGTON | DECEMBER 7, 2011

One of the last educational sessions on Tuesday night went into detail about oncofertility. I was expecting a talk I've heard before: doctors should inform patients of fertility options and what those options are. Instead, Teresa Woodruff, PhD, of the Oncofertility Consortium at Northwestern University went into so much more.

On top of the obvious – not being able to have children - Woodruff mentioned some of the psychosocial issues involving treatment-related sterility, including depression and increased anxiety in adult survivors of childhood cancer, which doesn't just include hopeful parents, but survivors who are entering the dating field – because who wants to start out on a first date with the bombshell of "I can't have kids."

While men are able to bank sperm before the start of cancer treatment, women have it a bit more complicated. Freezing embryos often requires a partner (or at least an anonymous donor) and harvesting eggs may not be an option for some patients. Two investigational methods are cryopreservation of ovarian tissue and oocytes, which include removing tissue before initiating cancer therapy and freezing it with the idea that it can be later transplanted back into the patient once they are cancer-free; however, the threat of re-introducing cancer cells is worrisome and it doesn't have a high success rate so far.

The Consortium is looking into a technique that grows follicles isolated from ovarian tissue. They're attempting to develop an artificial ovary derived from brown algae to cultivate the follicles. The follicles have been shown (in the lab) to produce hormones, contain oocytes and, in mice models, have produced live births.

They've been able to use the method in mice, but humans are much more complex, she acknowledges. There are also a bevy of questions in this field regarding legality, ethics and costs (CURE touches on these topics in "What to Expect When You're Not Expecting – Yet"). These are not simple questions to answer.

The first step, though, is knowing that "practice guidelines exist and recommend that the fertility threat associated with cancer treatment be discussed with all young patients," she says, and that "options do exist for men, women and children ... that's right for the patient and time of life."

No matter how serious the cancer or how young the patient, the conversation should be approached. And while it may seem like patients should know to ask by now, I still think it's the oncology team to start the conversation and offer options and referrals, if needed.

You can find more information on oncofertility on the Oncofertility Consortium's website at myoncfertility.org. It also offers a hotline (866-708-3378) for patients and survivors. There is also a smart phone app to download the patient guide and navigation tool.

• An update on the Cancer Genome Atlas for breast cancer
• Video blog: Test could spare some DCIS patients from radiation
• Video blog: HER2-targeted agents
• Video blog: Complications with brachytherapy in breast cancer
• Video blog: CLEOPATRA and pertuzumab in breast cancer

Arriving at the San Antonio Breast Cancer Symposium

BY ELIZABETH WHITTINGTON | DECEMBER 6, 2011

After a long flight from Memphis to San Antonio by way of Atlanta, I arrived at the San Antonio Convention Center near the Riverwalk. This year is shaping up to be an exciting program regarding breast cancer research, with about 8,000 attendees expected from around the world.

On my flight, I explained to an unsuspecting traveler that he would be arriving in the southern Texas town at a very exciting time; that this large breast cancer conference is always held in San Antonio in December. Unlike other oncology conferences that may change location every year, SABCS originated here 34 years ago and has stayed ever since.

The first presentations are scheduled for tomorrow morning, but there are a series of educational seminars that explore hot topics in treatment and biologic research, including sessions on reconstruction, biomarkers, new targeted pathways, treating early-stage disease and metastasis, as well as how to treat special populations - namely the very young and the elderly. Dr. Debu Tripathy, CURE's editor-in-chief and a practicing breast oncologist, will be blogging about how this year's presented research will translate to the clinical setting. (You can read his first post on what to expect this year here.) Our publisher, and two-time breast cancer survivor, Susan McClure, will be finding those patient advocates that SABCS is known for to report on how they are interpreting the information. I'll be doing a little bit of both.

To get the full recap of SABCS, follow our blogs (tagged SABCS2011) and sign up for our breast cancer newsletter at curetoday.com/newsletters. You can also follow along with the discussion on our Facebook fan page and on Twitter using the hashtag #sabcs.

Let us know what you'd like to hear about and if you have any questions for Dr. Debu. And if you're at SABCS blogging, advocating or just soaking it all in, let us know. We'll start a blogroll and post them here for those who are watching from near and far.

• For the Cure to a broken heart
• An update on the Cancer Genome Atlas for breast cancer
• Video blog: Test could spare some DCIS patients from radiation
• Video blog: HER2-targeted agents
• Video blog: Complications with brachytherapy in breast cancer

Aspirin delivers on colorectal cancer prevention

BY ELIZABETH WHITTINGTON | NOVEMBER 28, 2011

For years, aspirin has been touted as a way to prevent colorectal cancer, but medical groups have stopped short of recommending it because of potential side effects. However, a study published in The Lancet in October shows that at least one group could benefit from taking a couple of aspirin on a daily basis.

The CAPP2 (Colorectal Adenoma/carcinoma Prevention Programme) study followed 861 individuals with Lynch syndrome, a genetic condition that increases one's lifetime risk of colorectal cancer by about 70 percent, as well as endometrial and other cancers.

Individuals in the trial were randomized to receive 600-mg of aspirin or a placebo daily. After two years researchers saw no difference, but after continued follow-up, a delayed benefit did appear in the aspirin group. After 4.6 years, 4 percent of patients in the aspirin group developed colorectal cancer compared with 7 percent in the placebo group. The risk of other Lynch syndrome-associated cancers was also lower in the aspirin group – by around half. The study is designed for a 10-year follow-up, so expect to hear more on this study.

Because this was the first randomized study to look at the chemopreventive effects of aspirin in this high-risk group, further studies will need to be conducted to confirm the effect and to determine the optimum dose and length of treatment. CAPP3 will compare lower doses of aspirin to the 600 mg/day dose used in CAPP2.

For individuals at average risk, the benefits of daily aspirin may not outweigh the risks, which can include gastrointestinal bleeding. However, it may be worth talking to your doctor, especially if the disease runs in your family or you're already taking aspirin to lower your risk of heart attack. Recommendations for those at average risk include colorectal cancer screening from age 50 to 75.

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• Free webinars for patients and survivors