May 2015, Vol. 2, No. 3

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FDA Approves Opdivo (Nivolumab) for the Treatment of Patients with Previously Treated Metastatic Squamous Non–Small Cell Lung Cancer

Suresh Ramalingam, MD

Lung Cancer

Bristol-Myers Squibb Company announced that the Food and Drug Administration (FDA) has approved Opdivo (nivolumab) 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. Opdivo is the first and only PD-1 (programmed death-1) therapy to demonstrate overall survival (OS) in previously treated metastatic squamous NSCLC. Opdivo demonstrated significantly superior OS versus docetaxel, with a 41% reduction in the risk of death (hazard ratio, 0.59; 95% CI, 0.44-0.79; P = .00025), in a prespecified interim analysis of a phase 3 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).

“Bristol-Myers Squibb is committed to patients with lung cancer, and we are pleased to offer Opdivo as the first immuno-oncology therapy for patients who have previously treated metastatic squamous NSCLC,” said Lamberto Andreotti, Chief Executive Officer, Bristol-Myers Squibb. “Because lung cancer is one of the most commonly diagnosed cancers in the United States, with high mortality, there is a significant need for treatments that extend survival. We’re thankful to the many patients and healthcare providers that partnered with us to develop a new treatment that has the potential to address that unmet need.”

This approval is the second for Opdivo in the United States within 3 months and is based on the results of CheckMate -017 and CheckMate -063.

Opdivo is associated with immune-mediated pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, hypothyroidism and hyperthyroidism, other adverse reactions; and embryofetal toxicity.

Proven Superior Survival vs Standard of Care in a Phase 3 Clinical Trial

CheckMate -017 was a landmark phase 3, open-label, randomized, multinational, multicenter clinical trial that evaluated Opdivo (3 mg/kg intravenously over 60 minutes every 2 weeks) (n = 135) versus 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 end point of this trial was OS.

In January, the trial was stopped based on an assessment conducted by the Independent Data Monitoring Committee, which concluded that the study met its end point, demonstrating superior OS in patients receiving Opdivo compared with 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).

Opdivo is the only FDA-approved monotherapy to demonstrate proven superior OS compared with standard of care in more than 15 years in previously treated metastatic squamous NSCLC. 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). The hazard ratio was 0.59 (95% CI, 0.44-0.79; P = .00025). This hazard ratio translates to a 41% reduction in the risk of death with Opdivo compared with docetaxel.

“The FDA approval of 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 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.”

About the CheckMate -063 Trial and the Safety Profile of Opdivo

The safety profile of Opdivo in squamous NSCLC was established in CheckMate -063, a phase 2, single- arm, open-label, multinational, multicenter trial of Opdivo administered as a single agent in patients with metastatic squamous NSCLC who had progressed after receiving a platinum-based therapy and at least 1 additional systemic treatment regimen (n = 117). Patients received 3 mg/kg of 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 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. Opdivo was discontinued due to adverse reactions in 27% of patients. Twenty-nine percent of patients receiving 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, the study’s primary end point, 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, 1.7-8.8 months) after the start of Opdivo treatment. Seventy-six percent of Opdivo responders (13/17 patients) had ongoing responses with durability of response ranging from 1.9+ to 11.5+ months; 10 of these 17 patients (59%) had durable responses of 6 months or longer.

“The approval of 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. I applaud the FDA and Bristol-Myers Squibb for their work in making this important and first-of-its-kind treatment available to patients so quickly.”

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