Bristol-Myers Squibb Company has announced that the Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Opdivo (nivolumab) for two new indications – adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and adults with advanced renal cell carcinoma (RCC) after prior therapy. Both indications are supported by Phase 3 studies in which Opdivo demonstrated a survival benefit versus a standard of care. The CHMP positive opinions will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). Opdivo is already approved by the EC for advanced melanoma and previously treated advanced squamous NSCLC.
Michael Giordano, M.D., senior vice president, head of Development, Oncology, Bristol-Myers Squibb, commented, “We are committed to advancing our mission to make Opdivo available to a broader range of patients with a wide range of cancers who are in critical need of new treatment options. Today’s two positive CHMP opinions are important achievements and mean we are closer to reaching this goal for those with advanced non-squamous non-small cell lung cancer and renal cell carcinoma. We look forward to the European Commission's decision and the opportunity to bring an additional treatment option to these patients as quickly as possible."
In lung cancer, the CHMP adopted the positive opinion based on a review of the global Phase 3 study, CheckMate -057, which evaluated the survival of patients with non-squamous NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen. In the trial, Opdivo demonstrated superior overall survival (OS) in previously treated metastatic non-squamous NSCLC compared to chemotherapy, with a 27% reduction in the risk of death (HR: 0.73 [95% CI: 0.59, 0.89;p=0.0015]), based on a prespecified interim analysis. The median OS was 12.2 months in the Opdivo arm (95% CI: 9.7, 15.0) and 9.4 months in the docetaxel arm (95% CI: 8.0, 10.7). Fifty-one percent of patients were alive at one year in the Opdivo arm (95% CI: 45-56) vs. 39% in the docetaxel arm (95% CI: 33-45). The safety profile of Opdivo in CheckMate -057 was consistent with prior studies. In the overall patient population, which included both PD-L1 expressors and non-expressors, the most frequent serious adverse reactions in at least 2% of patients receiving Opdivo were pneumonia, pulmonary embolism, dyspnea, pleural effusions and respiratory failure. The most common adverse reactions in patients treated with Opdivo (reported in >20% of patients) were fatigue (49%), musculoskeletal pain (36%), cough (30%), decreased appetite (29%) and constipation (23%).
In renal cell carcinoma, the CHMP adopted the positive opinion based on a review of the Phase 3 study, CheckMate -025, which evaluated Opdivo versus everolimus in patients with advanced clear-cell RCC after prior therapy, with OS as the primary endpoint. Patients treated with Opdivo in this study achieved a more than five month improvement in OS with median OS of 25 months for Opdivo and 19.6 months for everolimus (hazard ratio: 0.73; [98.5% CI, 0.57-0.93; p=0.0018]), with OS benefit seen regardless of PD-L1 expression. Opdivo is the first and only anti-PD-1 therapy to demonstrate a significant survival benefit in this population through a randomized Phase 3 study. In addition, patients treated with Opdivo also experienced a significant improvement in their health-related quality of life and had significantly lower symptom burden compared to patients receiving everolimus. The safety profile of Opdivo in CheckMate -025 was consistent with prior studies. Serious adverse events occurred in 47% of patients receiving Opdivo. The most frequent serious adverse reactions reported in at least 2% of patients receiving Opdivo were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In the study, the most common adverse reactions in patients receiving Opdivo versus everolimus (reported in >20% of patients) were asthenic conditions (56% vs. 57%), cough (34% vs. 38%), nausea (28% vs. 29%), rash (28% vs. 36%), dyspnea (27% vs. 31%), diarrhea (25% vs. 32%), constipation (23% vs. 18%), decreased appetite (23% vs. 30%), back pain (21% vs. 16%), and arthralgia (20% vs. 14%).
Clinical results from CheckMate -057 and CheckMate -025 were presented at the 2015 European Cancer Congress, and published in The New England Journal of Medicine.