The benefit for breast cancer patients treated with Puma's neratinib was "awfully small" for a drug that causes "a lot of diarrhea," said Dr. Harold Burstein, a breast cancer expert from the Dana-Farber Cancer Institute.
Puma shares are down more than 9% to $177.04 in Monday trading.
Burstein spoke to me following presentation of results from the neratinib phase III "ExteNet" study at the American Society of Clinical Oncology (ASCO) annual meeting Monday. Puma is developing neratinib for the treatment of HER2-positive breast cancer patients in the extended adjuvant setting.
The absolute disease-free survival for neratinib was 93.9% compared to 91.6% for placebo -- a difference of 2.3 percentage points. The benefit, while statistically significant, is tough to call clinically meaningful for breast cancer patients given the drug's toxicity, Burstein said.
Forty percent of patients treated with neratinib experienced grade 3 diarrhea, which is defined as seven more stools per day, incontinence and hospitalization.
"This is not someone simply eating too many chili peppers and having a single bout of diarrhea," said Burstein.
After the study was conducted, Puma implemented a protocol in which patients are treated with anti-diarrhea medicines before taking neratinib. The presenter of the ExteNet study data on Monday noted that this strategy lowered the incidence of grade 3 diarrhea but it still occurred in up to 17% of patients.
Burstein was also concerned that two years of follow up in the study was too short to conclude with certainty the drug's real benefit for patients. This may cause FDA regulators to ask for more data.
Puma isn't expected to file for neratinib's approval until next year, so presumably, the company has time to collect more data on breast cancer patients in the ExteNet study. Subsequent data collection may be unreliable, however, because of numerous changes already made to the study.
Dr. Shanu Modi of Memorial-Sloan Kettering Cancer Center was charged with discussing the neratinib ExteNet results following their presentation. She concluded her talk with a question, "Is extended therapy with neratinib ready to be a new standard of care?"
Yes, if you only consider the positive breast cancer recurrence data, Modi concluded. But she then added that perhaps it's wiser to wait to see if neratinib can also prolong survival -- data which Puma does not yet have. She also raised concerns about neratinib's toxicity and wondered if the small benefit is worth the side effects, particularly in lower-risk patients.
During a Q&A session at the end of the ASCO presentation, an audience member said "neratinib seems like a terrible drug," referring to the high rate of diarrhea. Another ASCO attendee called the ExteNet results presented "unactionable" and criticized the study's short follow up.
Puma executives are meeting with investors and analysts on Monday night and will likely spend the bulk of their time trying to defend neratinib and counter the drug's chilly reception at the ASCO data presentation. The bigger challenge might be finding a buyer willing to acquire Puma.