Richard Pazdur, MD
The FDA has approved the anti–PD-1 agent nivolumab (Opdivo) for the treatment of patients with advanced squamous non–small cell lung cancer (NSCLC) who have progressed on or after platinum-based chemotherapy. The approval comes 3 months ahead of the FDA’s scheduled decision date.
The approval is based on data from the phase III CheckMate-017 trial in which nivolumab improved overall survival (OS) by 3.2 months versus docetaxel in previously treated patients with advanced or metastatic squamous cell NSCLC.
“The FDA worked proactively with the company to facilitate the early submission and review of this important clinical trial when results first became available in late December 2014,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval will provide patients and healthcare providers knowledge of the survival advantage associated with Opdivo and will help guide patient care and future lung cancer trials.”
The phase III open-label CheckMate-017 study involved 272 previously treated patients with advanced or metastatic squamous cell NSCLC. Participants were randomized to the fully human IgG4 monoclonal antibody nivolumab at 3 mg/kg intravenously every 2 weeks (n = 135) or docetaxel at 75 mg/m2 (n = 137) intravenously every 3 weeks.
Treatment with nivolumab improved OS by 41% versus docetaxel (9.2 vs 6.0 months; HR = 0.59; 95% CI, 0.44-0.79; P = .00025).
Beyond the primary OS endpoint, secondary endpoints included progression-free survival and objective response rate (ORR).
Bristol Myers Squibb (BMS), the manufacturer of nivolumab is working on a timetable for publication and presentation of the study data.
The approval was also supported by data from the open-label, single-arm, phase II CheckMate-063 study of nivolumab in NSCLC, which were presented at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology.
The study included 117 heavily pretreated patients with advanced squamous cell NSCLC. All patients had failed two or more systemic treatments and 65% of participants (n = 76) had previously failed three or more treatments. Seventy-six percent of patients were within 3 months of completion of their most recent therapy.
Nivolumab was administered at 3 mg/kg intravenously every 2 weeks until disease progression or treatment discontinuation.
At 11 months’ follow-up ORR, as assessed by an independent panel, was 15% (95% CI, 8.7-22.2), with a median duration of response that was not yet reached.
The estimated 1-year survival rate was 41% (95% CI, 31.6-49.7) and the median OS was 8.2 months (95% CI, 6.05-0.91).
An additional 26% of patients had stable disease for a median duration of 6 months (95% CI, 4.73-10.91), producing a disease control rate (ORR plus stable disease) of 41%. Responses were observed independent of PD-L1 status for patients with quantifiable PD-L1 expression.
Adverse events (AEs) of all types and grades occurred in 74% of patients; however, 85% of patients were able to receive at least 90% of their planned dose intensity.
Grade 3/4 drug-related AEs were reported in 17% of patients. The most common (≥2%) grade 3/4 AEs were fatigue (4.3%), pneumonitis (3.4%), and diarrhea (2.6%).
Discontinuations due to drug-related AEs of any grade occurred in 12% of patients. Two drug-related deaths (1 hypoxic pneumonia, 1 ischemic stroke) occurred in patients with multiple comorbidities and progressive disease.
BMS announced at the end of February that the FDA had granted a priority review to nivolumab for use in patients with previously treated, advanced, squamous NSCLC. The drug was initially approved in December 2014 for patients with unresectable or metastatic melanoma following treatment with ipilimumab (Yervoy) or a BRAF inhibitor.
“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, in a statement. “This milestone brings to fruition the long-held hope that immuno-oncology medicines can be significantly effective in this difficult-to-treat population.”