- New clinical data for Bristol-Myers Squibb's flagship checkpoint inhibitor Opdivo (nivolumab) presented Monday suggested the drug delivered a durable long-term benefit for some patients with advanced melanoma and non-small cell lung cancer (NSCLC).
- While Opdivo has already been approved in both cancer types, the results give a clearer picture of the overall survival benefit for the immmunotherapy over time. In advanced melanoma, for example, 64% of patients who received a combination of Opdivo and Bristol-Myers' older immunotherapy Yervoy (ipilimumab) were alive after two years.
- In that trial, known as Checkmate-067, treatment with Opdivo or the Opdivo/Yervoy duo reduced the risk of death by 45% and 37%, respectively, compared to Yervoy alone. Median overall survival in either Opdivo cohort had not yet been reached after a minimum of 28 months of follow-up.
Investigators affiliated with Bristol-Myers presented the new findings at the annual meeting of the American Association of Cancer Research in Washington, D.C. — one of the largest gatherings of cancer researchers each year.
The results are the first overall survival data to read out from the positive Checkmate-067 trial, which had originally led the Food and Drug Administration to approve Opdivo and Yervoy in advanced melanoma on an accelerated basis a little over a year ago.
After a minimum 28 months of follow-up, 17% of patients in the combo arm had a complete response, up from 12% at a previous 18-month analysis. A similar increase was seen in the Opdivo monotherapy arm, with 15% experiencing a complete response versus just under 10% at the previous analysis.
The combo was also more toxic, however. Treatment with the combo led to a Grade 3 or 4 adverse event in nearly 59% of patients, compared to 21% on Opdivo alone and 28% on Yervoy monotherapy. But no cumulative toxicity or new safety signals were identified, the company said. Two new treatment-related deaths in the 313-patient combo arm were also disclosed.
"Considering all of the study findings, first-line [Opdivo plus Yervoy] may represent a means to improve outcomes versus [Opdivo]," said study investigator Dr. James Larkin of the Royal Marsden Hospital. Larkin cautioned, however, that the study was not powered to statistically compare the Opdivo/Yervoy and Opdivo arms against each other, so that finding remains descriptive.
In addition to the Checkmate-067 results, follow-up data from an early, small Phase 1b study of Opdivo in second-line advanced NSCLC showed that 16% of patients were alive after five years — the longest survival follow-up available for a checkpoint inhibitor in that type of lung cancer.
Data cited by study investigator Julie Brahmer, an associate professor of oncology at John Hopkins' Sidney Kimmel Comprehensive Cancer Center, suggested the five-year survival rate for metastatic lung cancer is historically around 4%.
Twelve of the 16 patients who survived past five years did not receive any further therapy after treatment with Opdivo for a maximum of two years. Brahmer said the results suggest that patients don't need to be treated indefinitely with Opdivo, although more work needs to be done to define which patients stand to benefit the most.