On August 16, 2018, the Food and Drug Administration granted accelerated approval to nivolumab (Opdivo, Bristol-Myers Squibb Company Inc.) for patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy.
Approval was based on demonstration of a durable overall response rate (ORR) in a subgroup of patients from CheckMate-032 (NCT01928394), a multicenter, open-label trial in patients with metastatic solid tumors. This subgroup comprised 109 patients with metastatic SCLC, with disease progression after platinum-based therapy and at least one other prior line of therapy, regardless of tumor PD-L1 status. All patients received nivolumab 3 mg/kg by intravenous infusion over 60 minutes every 2 weeks.
The major efficacy outcome measures were overall response rate (ORR) and duration of response according to RECIST v1.1 as assessed by blinded independent central review. The ORR was 12% (95% CI: 6.5, 19.5). Responses were durable for 6 months or longer in 77%, 12 months or longer in 62%, and 18 months or longer in 39% of the 13 responding patients. PD-L1 tumor status did not appear to be predictive of response.
Safety data was evaluated in 245 patients with metastatic SCLC with disease progression following platinum-based chemotherapy and received at least one dose of nivolumab at a dose of 3 mg/kg every 2 weeks. The most common (≥20%) adverse reactions in CheckMate-032 were fatigue, decreased appetite, musculoskeletal pain, dyspnea, nausea, diarrhea, constipation and cough. Nivolumab was discontinued for adverse reactions in 10% of patients and 25% of patients had at least one dose withheld for an adverse reaction. Serious adverse reactions occurred in 45% of patients. The most frequent (≥2%) serious adverse reactions were pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration.
The recommended dose and schedule of nivolumab for this indication is 240 mg every 2 weeks over 30 min.
This application was granted Priority Review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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