Bristol Myers Squibb (NYSE: BMY) announced that the U.S. Food and Drug Administration (FDA) has approved Opdivo® (nivolumab) for adult patients with resectable non-small cell lung cancer (NSCLC) characterized by tumors measuring 4 cm or larger or node-positive cases, provided there are no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. This approval allows for neoadjuvant treatment in combination with platinum-doublet chemotherapy, followed by single-agent Opdivo as an adjuvant treatment after surgery, collectively referred to as perioperative therapy. The decision is based on findings from the CheckMate-77T trial, marking the second successful Phase 3 randomized trial involving an immunotherapy-based regimen.
Tina Cascone, MD, PhD, an associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, emphasized the importance of this approval: “Given the high rates of disease recurrence in patients with resectable NSCLC, there is a significant need for treatment options that can be administered both before and after surgery to target micrometastasis, reduce the risk of cancer returning, and enhance surgical success.” She noted that the combination of nivolumab and neoadjuvant chemotherapy offers improved event-free survival (EFS) compared to chemotherapy alone and shows potential for achieving a pathological complete response (pCR) in one in four patients.
The CheckMate-77T trial assessed the efficacy of the perioperative regimen involving neoadjuvant Opdivo with platinum-doublet chemotherapy followed by surgery and subsequent adjuvant Opdivo monotherapy (n=229), compared to neoadjuvant platinum-doublet chemotherapy combined with placebo followed by surgery and adjuvant placebo (n=232). Results demonstrated that the Opdivo group achieved significantly improved EFS, which was the primary endpoint, along with a high rate of pCR as a pre-specified secondary endpoint.
In the trial, the risk of disease recurrence, progression, or death was reduced by 42% (EFS Hazard Ratio [HR] 0.58; 95% Confidence Interval [CI]: 0.43 to 0.78; P=0.00025) for patients treated with Opdivo compared to the chemotherapy and placebo group, with a median follow-up of 25.4 months. Additionally, 70% of patients in the Opdivo arm demonstrated 18-month EFS, contrasted with 50% in the comparator arm. Furthermore, 25% of patients in the Opdivo group achieved pCR, compared to only 4.7% in the control arm, representing an estimated treatment difference of 20.5% (95% CI, 14.3 to 26.6).
However, Opdivo is associated with several warnings and precautions, including severe and potentially fatal immune-mediated adverse reactions such as pneumonitis, colitis, hepatitis, and nephritis, along with complications related to allogeneic hematopoietic stem cell transplantation (HSCT) and embryo-fetal toxicity. Treatment with Opdivo in combination with a PD-1 or PD-L1 blocking antibody alongside a thalidomide analogue and dexamethasone is not recommended outside of controlled clinical trials.
Wendy Short Bartie, senior vice president of U.S. Oncology and Hematology at Bristol Myers Squibb, highlighted the significance of this approval: “This milestone expands the role of Opdivo-based treatments and builds upon the foundation established by the FDA approval of neoadjuvant-only Opdivo plus chemotherapy for resectable NSCLC from the CheckMate-816 trial. With this new regimen, we are reinforcing our commitment to improving patient outcomes and expanding our thoracic portfolio in early-stage disease.”
For this indication, the recommended dose of Opdivo is 360 mg in combination with platinum-doublet chemotherapy on the same day every three weeks for up to four cycles or until disease progression or unacceptable toxicity occurs. Following surgery, Opdivo continues as a single-agent treatment at 480 mg every four weeks for up to 13 cycles (approximately one year) or until disease recurrence or unacceptable toxicity. The FDA had previously approved Opdivo for adult patients with resectable NSCLC in the neoadjuvant setting combined with platinum-doublet chemotherapy. Opdivo and its combinations have been approved in the neoadjuvant, adjuvant, or perioperative settings for four types of cancer: lung cancer, melanoma, bladder cancer, and esophageal/gastroesophageal junction cancer. Opdivo is now recognized as the only PD-1 inhibitor to demonstrate significant and clinically relevant benefits in NSCLC compared to chemotherapy in both neoadjuvant-only and perioperative regimens.
