Genentech’s Two-Drug Strategy Raises the Bar in Breast Cancer

12/7/11Follow @xconomy

Two drugs together aren’t always better than one, but today Genentech is making the argument that two antibody treatments in combination are the way to go for certain patients with breast cancer.

Genentech, the South San Francisco-based unit of Roche, is announcing today results from a clinical trial that shows patients were able to live, without their disease getting worse, for a median of an additional 6.1 months if they got an antibody drug called pertuzumab in addition to the usual trastuzumab (Herceptin) and chemotherapy. The results came from a study called Cleopatra, which enrolled 808 patients who were getting their first round of therapy for breast cancer that overexpresses the HER2 protein, and which had spread through the body. Researchers said patients on the new regimen of pertuzumab, trastuzumab and chemotherapy were able to keep their tumors from spreading for a median time of 18.5 months, compared with 12.4 months for those on the standard trastuzumab and chemo alone.

The findings are being presented today at the San Antonio Breast Cancer Symposium, and published online in the New England Journal of Medicine.

This study is important for Genentech because it has long dominated the field of HER2 amplified breast cancer, with its multi-billion dollar hit drug Herceptin. But patients eventually develop resistance to that drug, and competitors like GlaxoSmithKline’s lapatinib (Tykerb) have sought to further improve patient care and chip away at Genentech’s market share. Since the new Genentech antibody didn’t appear to add any toxicity to the heart, and researchers mostly saw mild diarrhea and white-blood cell depletion, Genentech is hoping this study will help pave the way for FDA approval to start selling the new antibody in tandem with the traditional one. Just this week, Genentech said it turned in its application to the FDA for approval of pertuzumab based on the results from the Cleopatra study, and Roche is also seeking approval from European regulators.

“This is huge. It is very uncommon to have a clinical trial show this level of improvement,” in slowing the spread of tumors, said Jose Baselga, the chief of hematology/oncology at Massachusetts General Hospital, in a statement released by the San Antonio conference organizers. “Most metastatic patients with HER2-positive breast cancer eventually stop responding to trastuzumab, so the fact that we now have an agent that can be added to current treatment to delay progression is very exciting.”

Scientists have been waiting for this kind of validation from clinical trials for years. The new Genentech drug is designed to bind to a different place on the HER2 molecule than trastuzumab, which Genentech has long wagered would provide a more complete blockade of the HER2 tumor-signaling pathway. The two-antibody strategy began to emerge in the medical community at last year’s San Antonio breast cancer conference, when it showed it could help completely wipe out tumors in about 46 percent of breast cancer patients getting prepped for surgery, compared 29 percent who did that well on existing standard of care.

“We have been studying the HER2 pathway for 30 years to bring personalized medicines to people with HER2-positive breast cancer,” said Hal Barron, Genentech’s chief medical officer, in a company statement. “These results show we may soon improve on the current standard of care, Herceptin plus chemotherapy, to further help people with this advanced form of the disease.”

While combining two antibody drugs sometimes raises concerns about adding extra toxicity, that didn’t appear to be a problem in the Cleopatra study. Researchers said that 69 of the 402 patients in the pertuzumab group died, compared with 96 of the 406 patients in the control group. Researchers will have to spend more time following up patients over time to see if the new antibody truly helps patients live longer in a statistically significant way, and if so, how much difference it really makes.

One other question that isn’t really a part of today’s presentation—but which will surely come up with insurers if pertuzumab wins FDA approval—is cost. New antibodies for cancer can sometimes cost as much as $100,000 a year, so insurers are surely going to want to see compelling evidence of benefit before reimbursing physicians for prescribing two expensive drugs instead of just one. But that will be an interesting business question for another day.

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