Pipeline

CURE, Spring 2010, Volume 9, Issue 1

The latest in cancer prevention, diagnosis, and treatment.

The agency based its decision on two phase 3 studies that showed progression-free survival—the amount of time patients lived without the disease getting worse—was longer when Rituxan was added to chemotherapy. In the first study, Rituxan plus chemotherapy extended median progression-free survival by eight months compared with chemotherapy alone (39.8 months versus 31.5 months). Similarly, patients receiving the Rituxan combination in the second study lived five months longer without their cancer progressing compared with patients receiving chemotherapy alone (26.7 months versus 21.7 months). Side effects of Rituxan can include fever, chills, headache, and, rarely, infusion reactions.

Rituxan becomes the third drug approved for CLL in the past two years. The FDA gave the green light to Arzerra (ofatumumab) last October, and Treanda (bendamustine) in March 2008.

About 16,000 people in the U.S. are diagnosed with CLL each year, making it the most common type of adult leukemia. For more information, visit www.rituxan.com or call 888-455-2220.

Already approved for non-Hodgkin lymphoma, Rituxan (rituximab) is now part of the arsenal for CD20-positive chronic lymphocytic leukemia. The Food and Drug Administration approved the monoclonal antibody in combination with Fludara (fludarabine) and Cytoxan (cyclophosphamide) in February.

There are many ways to fight cancer: Cut off its blood supply, poison it with chemotherapy, blast it with radiation. In December, the Food and Drug Administration “fast-tracked” their evaluation of a new approach for triple-negative breast cancer: Keep cancer cells from repairing ordinary DNA damage, and they will die.

The so-called PARP inhibitor BSI-201, made by BiPar Sciences, inhibits the activities of a key DNA repair enzyme known as poly ADP-ribose polymerase, or PARP, which is especially critical in cells that already have defects in other DNA repair pathways, such as BRCA1 and BRCA2.

Last year, researchers reported promising phase 2 results at the American Society of Clinical Oncology meeting: Women with triple-negative breast cancer who received BSI-201 in addition to chemotherapy (Gemzar [gemcitabine] and carboplatin) survived longer on average—12.2 months versus 7.7 months for chemotherapy alone. BSI-201 did not increase the frequency or severity of chemotherapy side effects.

A phase 3 trial with BSI-201 in metastatic triple-negative breast cancer is currently under way, with preliminary results possible as early as late summer or fall. The FDA uses fast-track status to speed up review of a drug that fills an unmet medical need for a serious disease such as cancers that do not have other effective therapies.

BSI-201 is also being tested in other types of breast cancer, as well as ovarian, uterine, lung, and brain cancers. For more information about clinical trials with BSI-201, call 866-668-2232 or e-mail clinicaltrials@BiParSciences.com.

After considering positive clinical trial results, the Food and Drug Administration granted accelerated approval to Tykerb (lapatinib) in combination with Femara (letrozole) as first-line treatment in postmenopausal patients with advanced HER2-positive breast cancer that is estrogen receptor-positive and/or progesterone receptor-positive. Tykerb is currently approved with Xeloda (capecitabine) for patients with advanced HER2-positive breast cancer who have previously received Herceptin (trastuzumab).

Median progression-free survival more than doubled with the addition of Tykerb to Femara (35 weeks versus 13 weeks). In its January announcement, the FDA noted it was too early to determine whether the combination improves overall survival.

In January, Genomic Health began selling a new test that measures the activity levels of 12 tumor genes to generate a “recurrence score” for stage 2 colon cancer. Clinical tests reported last year showed that risk designations of the Oncotype DX colon cancer test accurately predicted patient outcomes. Low-risk patients had an average three-year recurrence risk of 12 percent; intermediate-risk patients, 18 percent; and high-risk, 22 percent.

Although the test could not predict which high-risk patients were most likely to respond to chemotherapy after surgery, patients with a low recurrence score may choose to forego chemotherapy.

Merck, which makes the cervical cancer vaccine Gardasil, submitted new clinical data to the Food and Drug Administration at the end of last year as part of an ongoing effort to expand use of the vaccine to women ages 27 to 45. Gardasil, which targets the cancer-causing strains of the human papillomavirus, is currently approved to prevent cervical cancer and genital warts in females ages 9 to 26 who have not already been exposed to the virus, as well as for genital wart prevention in boys ages 9 to 26.

In 2008, the company sought approval to expand vaccine use to older women (after likely exposure to the virus), but the FDA requested data from completed trials. A decision from the agency could come as early as June.

Patients with advanced pancreatic neuroendocrine tumors lived twice as long without disease progression when taking Sutent (sunitinib), researchers said in January. Apple CEO Steve Jobs has this rare type of pancreatic cancer, which accounts for up to 5 percent of the estimated 42,500 pancreatic cancers diagnosed each year, according to the American Cancer Society.

Pfizer, the maker of Sutent, is asking for U.S., Canadian, and European approval to use the drug, which is currently approved in the U.S. for advanced kidney cancer and gastrointestinal stromal tumor, against advanced pancreatic neuroendocrine tumors, the company said.

Progression-free survival in patients taking Sutent was more than 11 months, compared with 5.5 months in those on a placebo, according to phase 3 data presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium in Orlando. The most significant side effects included neutropenia (12 percent of patients) and high blood pressure (9.6 percent). Sutent works by blocking various stages in cancer growth and proliferation.

www.sutent.com

Last year, an independent data monitoring committee stopped the trial early because Sutent showed significant benefit. For more information, visit or call 877-578-8368.

An experimental test for finding pancreatic cancer early has oncologists excited about the possibility of fighting the disease earlier and better. Pancreatic cancer is often diagnosed late, when it is difficult to treat and survival is low.

The new test, made by Immunomedics, uses a monoclonal antibody (clivatuzumab) to find and measure a blood protein (PAM4) present in almost all pancreatic cancers. The test picked up 81 percent of all stages of pancreatic cancer, researchers reported in January. The test won’t be available clinically for a few years.

British Medical Journal

Early-stage lung cancer patients who quit smoking double their chances of living five years, according to a study published in in January. Quitting is known to cut a person’s chances of getting lung cancer, but the effect of quitting on survival after diagnosis has been less clear.

The researchers reviewed 10 older studies that tracked early-stage lung cancer patients, smoking behavior, and survival. Overall, lung cancer patients who stopped smoking had five-year survival rates of 63 to 70 percent; those who kept smoking had rates of 29 to 33 percent.