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One of the surprising studies that came out included a phase 3 study of a drug that was withdrawn from the market last year called Mylotarg.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Mylotarg, also known as gemtuzumab ozogamicin, was approved back in 2000 for relapsed AML, but was withdrawn when follow-up studies showed the drug did not improve response rates and also increased the risk of a rare, but life-threatening liver complication called VOD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Because the drug has been withdrawn, it is typically not available to most patients.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.

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The Great American Smokeout

BY ELIZABETH WHITTINGTON | NOVEMBER 17, 2011

Today is the American Cancer Society's Great American Smokeout - a day smokers can circle on their calendars as the day they quit smoking.

While smoking has been most recognizably linked to lung cancer, quitting can also reduce your risk of bladder, head and neck, pancreatic and esophageal cancers - to name a few. And it's never too late to quit.

On my flight back from meeting with the American Cancer Society this week, I sat next to a man who mentioned that his father was recently diagnosed with lung cancer. He mentioned his father had been a smoker, but had quit and started treatment. It's never too late to quit. There have been several studies showing patients who quit smoking during treatment have a better response than those who continue to smoke.

Thankfully there are resources out there to help you to quit - and to help those you love to quit, including:

National Cancer Institute

SmokeFree.gov

Centers for Disease Control and Prevention

American Cancer Society

For those who continue to struggle with tobacco addiction, I thought it might be nice to hear from someone who has been there - President Obama. "The fact is, quitting smoking is hard. Believe me, I know."

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Drug approved to strengthen cancer patients' bones

BY ELIZABETH WHITTINGTON | SEPTEMBER 21, 2011

Late last week, on Sept. 16, the FDA approved denosumab to increase bone mass in patients receiving treatment for hormone-positive breast or prostate cancer who are at risk of bone fracture due to treatment.

Denosumab works by binding to RANKL, a protein involved in the formation, function and survival of osteoclasts, cells that break down bone tissue. In patients with hormone-positive cancers, treatments, such as aromatase inhibitors or androgen-deprivation therapy, can further weaken bones. The new approval of denosumab, under the brand name Prolia, is the first therapy to treat bone loss in patients with these types of cancers.

In mid-2010, Prolia received FDA approval to reduce the risk of fractures in women with osteoporosis. Xgeva, another form of denosumab, was approved in late 2010 to reduce fractures in certain advanced cancer patients with bone metastases.

The new indication was approved as Prolia because it is the same dosage used for women with osteoporosis - 60 mg subcutaneous injection that is give once every six months. Xgeva is given as a 120 mg injection every four weeks.

In the two trials reviewed by the FDA for this recent approval, Prolia increased bone mineral density when compared with placebo at one and two years follow-up. In prostate cancer patients, Prolia decreased new vertebral fractures at three years. Reported side effects included joint and back pain.

You can read about the approval and studies the FDA based its decision on here.

You can also view an animation of how certain cancer treatments affect bone tissue here.

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FDA examining heart issues seen with Zofran

BY ELIZABETH WHITTINGTON | SEPTEMBER 15, 2011

The FDA announced today that it is looking into safety issues with Zofran (ondansetron), specifically that it may carry a risk of abnormal heart rhythms in certain patients. Zofran is a common anti-emetic that can prevent and reduce nausea and vomiting due to cancer therapy.

Patients taking Zofran are advised not to stop taking the drug, but if they have questions, talk to their doctor. If they have irregular heart beats or feel faint or dizzy while taking the drug, to seek help immediately.

The drug has been associated with a risk of developing prolongation of the QT interval of the electrocardiogram, which can lead to an abnormal and potentially fatal heart rhythm, including Torsade de Pointes.

Zofran's drug label already contains information about potential heart problems, but the FDA will be revising the label to include specific patients who are at risk and who should be monitored. Patients at risk include those with underlying heart conditions, those who are predisposed to low levels of potassium and magnesium in the blood and patients who are receiving other medications that may lead to QT prolongation.

The FDA is also requiring GlaxoSmithKline to conduct a study to determine the degree to which Zofran may cause these heart issues. The study should be completed by summer 2012.

Patients are encouraged to report side effects related to the use of Zofran to the FDA's MedWatch Safety Information and Adverse Event Reporting Program at fda.gov/MedWatch/report.htm or call 800-332-1088.

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Xalkori approved for non-small cell lung cancer

BY ELIZABETH WHITTINGTON | SEPTEMBER 1, 2011

Late Friday, Aug. 26, the FDA announced it had granted accelerated approval of crizotinib for patients with advanced non-small cell lung cancer (NSCLC) who test positive for a specific gene mutation.

Crizotinib, which was given the brand name Xalkori, has made news since results of a clinical study showed that it delayed tumor progression in patients with NSCLC who had a mutation in the ALK gene. The approval was based on two studies that showed a response rate (shrinkage or stabilization of the tumor) of 50 percent and 61 percent, respectively. Overall survival is still being evaluated, and a phase 3 trial is ongoing for Xalkori to receive full approval from the FDA.

The mutated ALK (anaplastic lymphoma kinase) gene was first identified in lymphoma in 2004, then in lung cancer in 2007. The mutation actually occurs when parts of chromosome 2 breaks off and reattaches at a different location on a chromosome - fusing the ALK gene to the EML4 gene. In 2009, a review in the Journal of Thoracic Oncology showed the mutation to be a cause of about 4 percent of NSCLC cases. In less than a decade, researchers have identified a mutation, developed a drug to target it, tested the drug and succeeded in getting it approved.

Although it only applies to a small population of lung cancers, the total number of patients who could benefit from Xalkori is estimated to be around 5,000 to 11,000 patients a year.

"It's a good day for lung cancer patients, especially those with an EML4-ALK (mutation)," said Paul Bunn, MD, professor of medicine and the James Dudley chair in cancer research at the University of Colorado in Denver at a press briefing held on Aug. 30, who predicted that the recent approval marks a paradigm shift in the care and management of patients with lung cancer.

Also approved is a companion diagnostic test called Vysis ALK Break Apart FISH Probe Kit that will identify patients who have the abnormal gene. While the mutation is more commonly seen in nonsmokers, there are no set clinical factors that identify patients who may have the mutation. "We feel that it is appropriate to test all lung cancer patients," Bunn said.

The test will also prevent patients who would not respond to Xalkori from taking a drug that would not be beneficial – saving them time to try other therapies. Xalkori is a pill taken twice a day. Based on the approval, Xalkori is taken by itself, but there are studies looking at its effectiveness when combined with other drugs, including Tarceva (erlotinib), another targeted agent used in lung cancer. Side effects of Xalkori taken alone include diarrhea, vomiting, edema, constipation and vision disorders. It has also been associated with life-threatening pneumonitis (1.6 percent).

The cost of Xalkori is estimated to be $9,600 a month, and the test will likely cost $1,500. Pfizer, the drug's maker, has launched First Resource, a program to help patients pay for the medication (877-744-5675; xalkori.com).

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Cancer patients facing delays in receiving paclitaxel

BY ELIZABETH WHITTINGTON | AUGUST 9, 2011

The FDA released information today regarding manufacturing delays and an increase in demand for paclitaxel injection, a generic drug used for many different types of cancers. (You can read the full brief at FDA Drug Shortages.)

This marks only the latest cancer drug shortage. Problems with paclitaxel availability were first announced in May (more information can be found in Drug Shortages Leave Cancer Patients at Risk via Medpage Today).

The New York Times published an excellent opinion piece this past weekend by Ezekiel J. Emanuel (Shortchanging Cancer Patients) that explained how and why so many of these drug shortages are happening -- all of which are generic and inexpensive drugs.

We'll be reporting more on this topic in an upcoming CURE issue, so stay tuned. In the meantime, let us know if and how you've been affected by the recent drug shortages.

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Breast cancer research meeting sets record

BY ELIZABETH WHITTINGTON | JULY 25, 2011

Just received word that this year's San Antonio Breast Cancer Symposium has received a record number of abstracts with 1,641 abstracts submitted by researchers from around the world. This breaks the previous record of 1,464 made in 2009.

It remains to be seen how many or what type of abstracts will be presented, though. Abstracts are usually not released until just days before the meeting, and with the conference held Dec. 6-10, that's a long time to wait.

In the meantime, we have the ASCO Breast Cancer Symposium being held Sept. 8-10. Some of the research presented will include detection and imaging, triple-negative breast cancer, survivorship issues, hormone-positive breast cancer, bone health, neuropathy and treating young breast cancer patients.

You can follow CURE's coverage of these two meetings by signing up for our breast cancer newsletter here.

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A unanimous recommendation for Adcetris for lymphoma

BY ELIZABETH WHITTINGTON | JULY 14, 2011

Brentuximab vedotin is one step closer to being approved for Hodgkin lymphoma and anaplastic large cell lymphoma after an advisory panel voted that it does provide a viable new treatment option for patients.

We reported on the lymphoma drug, which has a proposed brand name of Adcetris, when the results of a phase 2 trial were announced at the American Society of Hematology meeting this past December. (Read about it here.)

The FDA advisory committee voted 10-0 to recommend accelerated approval for brentuximab vedotin in relapsed or refractory Hodgkin lymphoma and ALCL, which means that follow-up trials will need to confirm benefit before it can get full approval. The FDA also granted it priority review, meaning an approval could come as early as Aug. 30.

Brentuximab vedotin targets the CD30 antigen on the surface of lymphoma cells. Side effects include peripheral neuropathy, fatigue, nausea, upper respiratory tract infection and diarrhea.

Another interesting note is that brentuximab vedotin combines a CD30-targeted antibody with the cancer toxin auristatin. It has been touted as the first possible approved antibody-drug conjugate (ADC). T-DM1 (also called trastuzumab emtansine) also falls in this category and combines the approved antibody Herceptin with the drug maytansine (the DM1 part). It has shown potential against breast cancer.

While this is considered a new class of drugs, Mylotarg (gemtuzumab ozogamicin), approved in 2001, is also a type of conjugate, combining an antibody with a calicheamicin. Ironically, Mylotarg, after spending about 10 years on the market to treat acute myeloid leukemia, was pulled after follow-up trials revealed it offered no benefit. Let's hope brentuximab vedotin and T-DM1 don't share a similar fate. So, while brentuximab vedotin may not necessarily be the first approved antibody-drug conjugate, it may well be the only one for a time.

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Early-phase melanoma study adds to "Melanoma" ASCO

BY ELIZABETH WHITTINGTON | JUNE 5, 2011

To add to what appears will be a melanoma-focused ASCO meeting (American Society of Clinical Oncology) this year, a phase 1/2 trial of a combination of experimental targeted agents looks to be generating interest as well.

On Saturday, researchers revealed that two targeted therapies, still going by their compound names of GSK212 and GSK436 (both are developed by the same company, GSK), worked synergistically together against metastatic melanoma.

GSK436 works against the same mutated BRAF gene that vemurafenib does (which you will hear about later in the meeting and the summer issue of CURE). The other agent works against MEK.

While BRAF inhibitors appear to have success against melanoma, the researcher presenting the data, Jeffrey Infante, MD, says the effects isn't durable, which is where the MEK inhibitor comes in. The combination had a high response rate (81 percent), either reducing tumor size or preventing future tumor growth in many patients.

Another interesting aspect of the trial is that when combined, the two drugs seem to have fewer side effects, including reduced incidence of squamous cell carcinoma and an acne-like rash. Infante said they weren't quite sure why the combination produced less side effects, but it could be because BRAF and MEK are on the same signaling pathway.

The next step of the trial is to continue accruing patients in the phase 2 portion of the study to continue looking at the best possible dose, including different doses for GSK436 with GSK212 and GSK212 alone. Infante says the trial is accruing quickly and he expects to finish enrollment of 150 patients in just a couple of months.

The study highlights that combinations could be key to melanoma progress. Add to it the recent news of two major drug companies' unique collaboration on a study combining newly approved Yervoy and experimental drug, vemurafenib, the field of melanoma is receiving the attention so many melanoma patients desperately need.

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Investigational drug for GIST is on the fast track

BY ELIZABETH WHITTINGTON | MAY 13, 2011

The Food and Drug Administration has decided to grant regorafenib fast-track status. The drug is in phase 3 testing for the treatment of gastrointestinal stromal tumors (GIST), a rare type of sarcoma. Fast tracking typically helps move drugs that fill unmet needs and treat serious conditions, such as GIST, as fast as possible through the pipeline.

The phase 3 clinical trial, which started in January, will be examining 170 patients with inoperable GIST who will receive either regorafenib or placebo. (If patients who are on placebo have disease progression, they may be allowed to receive regorafenib.) Data from a phase 2 trial of regorafenib will be presented next month at the annual meeting of the American Society of Clinical Oncology.

Other drugs approved for GIST include Gleevec (imatinib) and Sutent (sunitinib). Patients in the phase 3 trial will have progressed on either drug. Unlike Gleevec, which targets one specific mutation called bcr-abl, regorafenib is a multikinase inhibitor, acting against several signals, including VEGF, RAF and KIT.

For more on fast-track status and other drug approval processes, see "A Primer on How Faster Approval Works." For more information on GIST, the organizations listed below have resource, educational materials and support services:

GIST Support International
gistsupport.org
215-340-9374
E-mail: gsi@gistsupport.org
This organization is dedicated to the support of GIST patients, families and friends, and the ongoing research required to treat and cure gastrointestinal stromal tumors.

Life Raft Group
liferaftgroup.org
973-837-9092
The Life Raft Group is a non-profit, Internet-based organization providing support through education and research to patients with gastrointestinal stromal tumors. For pediatric GIST patients, the Life Raft Group also hosts pediatricgist.org, which offers information, newsletters, community and resources.

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