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June 17, 2015 – Bristol Myers Squipp recently announced that the U.S. Food and Drug Administration (FDA) has approved Nivolumab (Opdivo) injection, for intravenous use, for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Nivolumab (Opdivo) is the first PD-1 (programmed death receptor-1) therapy to demonstrate overall survival in previously treated metastatic squamous NSCLC. Nivolumab (Opdivo) demonstrated significantly superior overall survival (OS) vs. docetaxel, with a 41% reduction in the risk of death (hazard ratio: 0.59 [95% CI: 0.44, 0.79; p=0.00025]), in a prespecified interim analysis of a Phase III clinical trial. The median OS was 9.2 months in the Opdivo arm (95% CI: 7.3, 13.3) and 6 months in the docetaxel arm (95% CI: 5.1, 7.3).
In this context, CheckMate -017 was a landmark Phase III, open-label, randomized, multinational, multicenter clinical trial that evaluated Nivolumab (Opdivo) (3 mg/kg intravenously over 60 minutes every two weeks) (n=135) vs. standard of care, docetaxel (75 mg/m2 intravenously administered every 3 weeks) (n=137), in patients with metastatic squamous NSCLC who had progressed during or after prior platinum doublet-based chemotherapy regimen. This trial included patients regardless of their PD-L1 (programmed death ligand-1) status. The primary endpoint of this trial was overall survival (OS). The trial was stopped based on an assessment conducted by the independent Data Monitoring Committee (DMC), which concluded that the study met its endpoint, demonstrating superior OS in patients receiving Nivolumab (Opdivo) compared to docetaxel. The prespecified interim analysis was conducted when 199 events (86% of the planned number of events for final analysis) were observed (86 in the Opdivo arm and 113 in the docetaxel arm).
Currently, Nivolumab (Opdivo) is the only FDA-approved monotherapy to demonstrate proven superior OS compared to standard of care in more than 15 years in previously treated metastatic squamous NSCLC. “The FDA approval of Nivolumab (Opdivo)introduces an entirely new treatment modality that has demonstrated unprecedented results for the treatment of previously treated metastatic squamous NSCLC, with the potential to replace chemotherapy for these patients,” said Dr. Suresh Ramalingam, MD, Professor and Director of Medical Oncology, Winship Cancer Institute of Emory University. “This milestone brings to fruition the long-held hope that immuno-oncology medicines can be significantly effective in this difficult-to-treat population.”
Therapy of eligible patients with Nivolumab (Opdivo) comes with a price, however. The clinical safety profile of Nivolumab (Opdivo) in squamous NSCLC was established in CheckMate -063, a Phase II single-arm, open-label, multinational, multicenter trial of Nivolumab (Opdivo), administered as a single agent in patients with metastatic squamous NSCLC who have progressed after receiving a platinum-based therapy and at least one additional systemic treatment regimen (n=117). Patients received 3 mg/kg of Nivolumab (Opdivo) administered intravenously over 60 minutes every 2 weeks. This trial included patients regardless of their PD-L1 status. The most common adverse reactions (reported in ≥20% of patients) were fatigue (50%), dyspnea (38%), musculoskeletal pain (36%), decreased appetite (35%), cough (32%), nausea (29%), and constipation (24%). Serious adverse reactions occurred in 59% of patients receiving Nivolumab (Opdivo). The most frequent serious adverse reactions reported in ≥2% of patients were dyspnea, pneumonia, chronic obstructive pulmonary disease exacerbation, pneumonitis, hypercalcemia, pleural effusion, hemoptysis, and pain. Nivolumab (Opdivo)was discontinued due to adverse reactions in 27% of patients. Twenty-nine percent of patients receiving Nivolumab (Opdivo) had a drug delay for an adverse reaction.
With at least 10 months of minimum follow up for all patients, the confirmed objective response rate (ORR), the study’s primary endpoint, was 15% (17/117) (95% CI = 9, 22) of which all were partial responses. The median time to onset of response was 3.3 months (range: 1.7 to 8.8 months) after the start of Nivolumab (Opdivo)treatment. Seventy-six percent of Nivolumab (Opdivo) responders (13/17 patients) had ongoing responses with durability of response ranging from 1.9+ to 11.5+ months; 10 of these 17 (59%) patients had durable responses of 6 months or longer.
“The approval of Nivolumab (Opdivo) for the treatment of previously treated metastatic squamous non-small cell lung cancer is a major advancement in delivering extended survival for patients fighting this deadly disease,” said Andrea Ferris, President and Chairman, Lungevity Foundation. “We are very excited for an immuno-oncology therapy to enter the market and offer options and hope for many of our patients.
Previously, Nivolumab (Opdivo) was approved by the FDA for the tratment of advanced melanoma.