Clinical Trial MARIANNE

Clinical Trial MARIANNE has been in the news since pharmaceutical maker Roche announced the preliminary results on December 18. In MARIANNE, a Phase III study, researchers randomized 1095 women with metastatic HER2-positive breast cancer into three arms: T-DM1 with Perjeta (the same treatment that I'm getting), T-DM1 alone, and Herceptin plus standard chemotherapy drugs (either docetaxel or paclitaxel), which is the current standard of care. The primary endpoints of the study were progession-free survival (PFS) and the incidence of adverse events, while secondary endpoints included overall survival, response rates, and duration of response. 

In what came as a surprise to both the medical oncology community and Roche's investors, no significant difference in PFS was found between the three arms. This was counter to both laboratory models and the results of the Phase II trial that preceded MARIANNE, in which TDM-1 had shown more than 50% improvement in PFS over the standard of care. The principal investigator of the trial, Dr. Edith Perez, said that her team would be spending the coming weeks dissecting the test results to pinpoint the reason for TDM-1's lackluster performance in the trial. In the meantime, Roche saw a sizable drop in stock price amid the perception that the trial results would hamper the clinical usage of TDM-1 (patents for Herceptin, also a Roche product, are expiring, and a generic form of the drug has already hit the market in India).

Based on everything I have read and heard, I too am surprised at the trial results, and I am eager to learn more about how this happened. However, I am more surprised - outraged even - that patient quality of life isn't even a consideration in the discussion about TDM-1 versus standard chemo plus Herceptin. I get that these patients are seriously ill and the highest priority is stopping the progression of their disease. I get that without better drugs, many if not most of these patients will die within months or years of their treatment, so the primary goal has to be better drugs. However, if Treatment A and Treatment B have the identical ability (or inability) to stop the disease, but Treatment A allows the patient to go on with her life, however long that may be, and continue with her work and play as long as she can, while Treatment B makes her feel like she is dying even more than the cancer itself - how could Treatment A not be seen as superior? And how could it not be inhumane to deny Treatment A to these patients? And yet, not one of the articles that I've read about MARIANNE have raised this point. Even Roche, who has everything to gain by making this argument, has not. 

You might think that "the incidence of adverse events" that is one of the trial's primary endpoints is about side effects, but it actually only tracks potentially life-threatening complications like leukopenia, which is a dangerously low white blood cell count. Fatigue, insomnia, nausea, bone pain, neuropathy, swelling of the hands and feet, constipation, diarrhea, hair loss, weight loss, weight gain, nail damage, "chemo brain", anxiety, and depression do not count as adverse events from the perspective of these studies, including my own trial, KRISTINE. But from the perspective of the patients, these side effects are often more destructive to their lives than their cancers are. Add to that the traumas of surgery and, in some cases, the side effects of radiation, and I think only the most cold-hearted among us could fail to feel that these women deserve a break. For women with HER2-positive breast cancer, TDM-1 can be that break, at least until something better is found. The idea that these women may not have that option because the only acknowledged measure of success is PFS is infuriating to me. We all want a chance at a longer life - but we also want whatever life we have to be the best that it can be.

Information from www.onclive.com.