FDA Approves Neoadjuvant Nivolumab/Chemotherapy for Resectable NSCLC

The FDA has granted approval to nivolumab (Opdivo) in combination with platinum-doublet chemotherapy as neoadjuvant treatment for adult patients with resectable non-small cell lung cancer (NSCLC), announced Bristol Myers Squibb, in a press release.¹

The approval is supported by findings from the phase 3 CheckMate-816 clinical trial (NCT02998528). In the study nivolumab plus platinum chemotherapy achieved a 37% reduction in the risk of progression, recurrence or death versus chemotherapy alone (HR, 0.63; 95% CI, 0.45-0.87; P =.0052). The median event-free survival was 31.6 months (95% CI: 30.2 to not reached [NR]) compared with 20.8 (95% CI: 14.0 to 26.7) in the chemotherapy-alone arm.

CheckMate-816 is an international, randomized, open-label study investigating the combination of nivolumab and ipilimumab (Yervoy) or nivolumab plus platinum doublet chemotherapy versus platinum doublet chemotherapy alone in patients with early-stage NSCLC. Interim analysis results from the study show that nivolumab plus chemotherapy showed a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) versus chemotherapy alone when administered prior to surgery, achieving a key primary end point in CheckMate-816.²

Results for the nivolumab/chemotherapy cohort were presented during the American Association for Cancer Research Annual Meeting 2021. In a cohort of 358 patients, the pCR was 24% with nivolumab/chemotherapy compared with 2.2% with chemotherapy alone (odds ration [OR]. 13.94, 99% CI, 3.4%-55.75%; P <.0001).³

“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, in a press release. “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. Today’s announcement reinforces the need to increase the rates of NSCLC screening and early detection, and for patients to discuss treatment options with their providers.”

Assessments of the secondary end points including overall survival (OS), major pathologic response (MPR), and time to death or distant metastases showed that 4 times as many patients treated with nivolumab plus chemotherapy achieved a MPR (36.9%) compared with those 8.9% in of those treated with chemotherapy (OR, 5.70, 95% CI: 3.16-10.26).

Overall, nivolumab/chemotherapy was well-tolerated with no new safety signal observed. Thirty-four percent of those treated with the experimental combination experienced grade 3/4 treatment-related adverse events compared with 37% of the chemotherapy-alone arm. It was also noted by investigators that surgery was not often canceled due to AEs.

In the nivolumab plus chemotherapy arm, 83% of patients underwent surgery versus 75% of the chemotherapy-only arm. Further, a higher percentage of patients who received nivolumab/chemotherapy has R0 resection (83%) compared with the chemotherapy-alone arm (78%).

In addition to patients with early-stage NSCLC being treated in the neoadjuvant setting, nivolumab-based therapies have shown efficacy and safety for the treatment of other lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer, and melanoma.

“At Bristol Myers Squibb, we are leading innovative science in the use of immunotherapy in earlier stages of cancer and are committed to bringing these options to patients,” said Adam Lenkowsky, senior vice president and general manager, US Cardiovascular, Immunology and Oncology at Bristol Myers Squibb, in the press release.¹ “Today’s approval builds on that commitment and expands the role of Opdivo-based treatment in NSCLC, the most common form of lung cancer, so patients may benefit earlier in the course of their disease.”

_REFERENCES:

_{1. U.S. 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 4, 2022. https://bit.ly/3MmyokZ}

_{2. U.S. Food and Drug Administration accepts for priority review Bristol Myers Squibb’s application for Opdivo (nivolumab) plus chemotherapy as neoadjuvant treatment for resectable non-small cell lung cancer. News release. February 28, 2022. Accessed February 28, 2022. https://bit.ly/3Hu0pmY}

_{3. Neoadjuvant Opdivo (nivolumab) Plus chemotherapy significantly improves pathologic complete response in patients with resectable non-small cell lung cancer in phase 3 CheckMate -816 Trial. News release. April 10, 2021. Accessed February 28, 2022. https://bit.ly/3C3ZFEi}