The Food and Drug Administration (FDA) has approved Opdivo® (nivolumab) with platinum-doublet chemotherapy as neoadjuvant treatment for adults with resectable (tumors ≥4cm or node positive) non-small cell lung cancer (NSCLC).
The approval was based on data from the randomized, open-label phase 3 CHECKMATE-816 trial (ClinicalTrials.gov Identifier: NCT02998528), which evaluated the efficacy and safety of nivolumab, a programmed death receptor-1 blocking antibody, plus platinum-doublet chemotherapy in adults with resectable, early stage NSCLC.
Patients were randomly assigned 1:1 to receive nivolumab plus platinum-doublet chemotherapy (n=179) or platinum-doublet chemotherapy alone (n=179). Chemotherapy consisted of paclitaxel plus carboplatin, pemetrexed plus cisplatin, or gemcitabine plus cisplatin. The coprimary endpoints were event-free survival (EFS) and pathological complete response (pCR).
Results showed that treatment with nivolumab plus chemotherapy significantly improved EFS, with a 37% reduction in the risk of progression, recurrence, or death compared with chemotherapy alone (hazard ratio, 0.63; 95% CI, 0.45-0.87; P =.0052). Median EFS was observed to be 31.6 months (95% CI, 30.2-not reached [NR]) for nivolumab plus chemotherapy and 20.8 months (95% CI, 14-26.7) for chemotherapy alone.
Additionally, 24% (95% CI, 18-31) of patients treated with nivolumab plus chemotherapy achieved pCR compared with 2.2% (95% CI, 0.6-5.6) of those treated with chemotherapy alone (estimated treatment difference 21.6%; 95% CI, 15.1-28.2; P <.0001).
An interim analysis of overall survival data resulted in a hazard ratio of 0.57 (95% CI, 0.38-0.87), which did not cross the boundary for statistical significance. The most common adverse reactions reported with the combination therapy were nausea, constipation, fatigue, decreased appetite, and rash.
“Given the rates of disease recurrence in patients with resectable NSCLC, additional treatment options are needed that can be given before surgery to help improve the chance of successful surgical treatment and support the goal of reducing the risk of cancer returning,” said Mark Awad, MD, PhD, CheckMate -816 study investigator and clinical director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute. “The approval of nivolumab with platinum-doublet chemotherapy marks a turning point in how we treat resectable NSCLC and it enables us to use immunotherapy and chemotherapy as neoadjuvant treatment for patients before surgery.”
- US Food and Drug Administration approves Opdivo® (nivolumab) with chemotherapy as neoadjuvant treatment for certain adult patients with resectable non-small cell lung cancer. News release. Bristol Myers Squibb. March 4, 2022. Accessed March 7, 2022. https://www.businesswire.com/news/home/20220301006264/en/U.S.-Food-and-Drug-Administration-Approves-Opdivo%C2%AE-nivolumab-with-Chemotherapy-as-Neoadjuvant-Treatment-for-Certain-Adult-Patients-with-Resectable-Non-Small-Cell-Lung-Cancer
- Opdivo. Package insert. Bristol Myers Squibb; 2022. Accessed March 7, 2022. https://packageinserts.bms.com/pi/pi_opdivo.pdf