On March 4, the US Food and Drug Administration (FDA) approved nivolumab (Opdivo) in combination with platinum-doublet chemotherapy every three weeks for three cycles for adult patients with resectable NSCLC in the neoadjuvant setting. Nivolumab plus chemotherapy is approved regardless of PD-L1 status.
The approval is based on the CheckMate 816 trial, the first positive phase III trial of an immunotherapy-based combination administered prior to surgery for resectable NSCLC.1 The primary endpoints of the trial were event-free survival (EFS) and pathologic complete response (pCR). The study compared nivolumab plus platinum-doublet chemotherapy to platinum-doublet chemotherapy alone.
In the trial, when given before surgery, nivolumab plus chemotherapy resulted in a statistically significant improvement in EFS with a 37% reduction in the risk of progression, recurrence or death compared to chemotherapy alone. Nivolumab plus chemotherapy yielded a median EFS of 31.6 months compared to 20.8 months for patients treated with the “active” control arm of chemotherapy alone with a HR of 0.63 (95% CI: 0.45 to 0.87) and a p value of 0.0052.
The interim analysis for OS shows a HR of 0.57 (95% CI: 0.38-0.87), though this OS comparison has not (yet) crossed the boundaries for statistical significance. Additionally, 24% of patients treated with nivolumab plus chemotherapy achieved pCR, compared to 2.2% of patients treated with chemotherapy alone.
“These data are very exciting and potentially game-changing,” said Corey Langer, MD, ILCN Editor. “However, there has not yet been a formal presentation or peer-reviewed publication of the data; nor do we have any data on EFS or OS by PD-L1 status, stage, or depth of response, which will help inform clinical decision-making. Presumably, all of this will be forthcoming when the trial data are presented at the AACR (American Association for Cancer Research) annual meeting next month.”
Dr. Langer said he believes these results may have the greatest impact in potentially resectable stage IIIA NSCLC, where surgery upfront has not been the established standard of care.
The nivolumab approval was granted under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible. The review was also conducted under the FDA’s Project Orbis initiative, which enabled concurrent review by the health authorities in Australia, Canada, and the UK, where the application remains under review.
The EFS data from the phase III CheckMate 816 trial will be presented at the 2022 AACR Annual Meeting, which takes place April 8-13 in New Orleans.