Nivolumab Indication in Small Cell Lung Cancer Withdrawn from US Market

Bristol Myers Squibb has withdrawn the indication of nivolumab (Opdivo) for the treatment of patients with small cell lung cancer (SCLC) who had disease progression after a platinum-based chemotherapy and at least 1 other line of therapy from the US market following a consultation with the FDA, the company announced in a press release.¹

The agent previously received accelerated approval from the FDA in 2018 based on data from surrogate end points of the phase 1/2 CheckMate-032 clinical trial in patients with advanced or metastatic solid tumors. There were encouraging response rates and duration of response in patients with SCLC, but subsequent confirmatory studies failed to meet their primary end points of overall survival (OS) with nivolumab, including 2 phase 3 clinical trials, CheckMate-451 (NCT02538666) and CheckMate-331 (NCT02481830).

The indication is being withdrawn in accordance with the FDA’s standard procedures for evaluating accelerated approvals that have not met post-marketing requirements and as part of a broader industry-wide evaluation.

“We believe in the power of science to address some of the most challenging diseases of our time, and so we pursue innovations with the goal of transforming patients’ lives,” said Abderrahim Oukessou, MD, vice president, Thoracic Cancers Development Lead, Bristol Myers Squibb, in a statement. “Although we are disappointed by the withdrawal, we appreciate that the FDA shared our commitment to bringing an innovative new therapy to patients with high unmet need when the science pointed in that direction. Similarly, we respect the FDA’s efforts to evaluate accelerated approvals across the industry to ensure the integrity of this important program.”

Nivolumab was the first new therapy to receive FDA approval in this setting for nearly 20 years, providing hope to patients with SCLC, an aggressive and difficult-to-treat cancer. This therapy has evolved and lead to the availability of more treatment options for patients with SCLC across lines of therapy.

In the CheckMate-032 study, the objective response rate was 12% with nivolumab (95% CI, 6.5%-19.5%), including partial responses in 11% and complete responses in 0.9%. The median duration of response was 17.9 months, and more than half of the patients (62%) had experienced a continued response at 1 year. In addition, 39% continued to respond at 18 months.²

Despite these encouraging findings, the confirmatory CheckMate-451 study demonstrated that nivolumab maintenance failed to provide an OS advantage compared with placebo either alone (HR, 0.84; 95% CI, 0.69-1.02) or in combination with ipilimumab (Yervoy; HR, 0.92; 95% CI, 0.75-1.12; P = .3693).³ Topline findings from the CheckMate-331 clinical trial also demonstrated that single-agent nivolumab did not improve OS compared with standard chemotherapy among patients with relapsed SCLC after platinum-based chemotherapy.⁴

The PD-1 immune checkpoint inhibitor harnesses the body’s immune system in order to restore anti-tumor immune response, and by harnessing the body’s own immune system, nivolumab has become an important agent for multiple cancer types. The long-term survival benefits of nivolumab in complex diseases, such as thoracic cancers, have been established.¹

Nivolumab is approved under multiple indications either alone as monotherapy or in combination with ipilimumab. These indications extend to select populations of patients with melanoma, non–small cell lung cancer, mesothelioma, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, colorectal cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma.

_References

_{1. Bristol Myers Squibb statement on Opdivo (nivolumab) small cell lung cancer U.S. indication. News Release. December 29, 2020. Accessed January 4, 2021. https://bit.ly/2X5PVFK}

_{2. Antonia SJ, Lopez-Martin JA, Bendell JC, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016;17(7):883-895. doi:10.1016/S1470-2045(16)30098-5.}

_{3. Owonikoko T, Kim H, Govindan R, et al. Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (chemo): Results from the double-blind, randomized phase III CheckMate 451 study. Presented at: 2019 European Lung Cancer Congress; April 11-13, 2019; Geneva, Switzerland. Abstract LBA1.}

_{4. Bristol-Myers Squibb announces phase 3 CheckMate-331 study does not meet primary endpoint of overall survival with Opdivo versus chemotherapy in patients with previously treated relapsed small cell lung cancer. News release. Bristol Myers Squibb. October 12, 2018. Accessed December 30, 2020. https://bit.ly/35ajFWx}