FDA Approves Bristol Myers Squibb’s Opdivo in Combination with Chemotherapy for Resectable Non-Small Cell Lung Cancer

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The FDA has approved Bristol Myers Squibb's (BMS) Opdivo (nivolumab) in combination with chemotherapy for the perioperative treatment of adult patients with resectable non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) rearrangements. The newly approved regimen includes neoadjuvant treatment (Opdivo with platinum-doublet chemotherapy), followed by surgery, and adjuvant single-agent Opdivo. Approval was based on results of the CheckMate-77T trial, which demonstrated that the regimen significantly improved event-free survival (EFS) and pathologic complete response (pCR) compared to chemotherapy alone.¹

“Given the rates of disease recurrence in patients with resectable NSCLC, there is a clear need for options that can be administered before and after surgery that may target micrometastasis, help reduce the risk of cancer returning and improve the chance of successful surgical treatment,” said Tina Cascone, MD, PhD, associate professor, thoracic/head and neck medical oncology, The University of Texas MD Anderson Cancer Center, in a press release. “This approval is a step forward for patients with resectable disease, as the perioperative nivolumab plus neoadjuvant chemotherapy regimen can offer an improved EFS compared with neoadjuvant chemotherapy alone and has the potential for achieving a pCR in one in four patients.”

The Phase III randomized, double-blind, multi-center CheckMate-77T trial evaluated neoadjuvant Opdivo in combination with platinum-doublet chemotherapy followed by surgery and single-agent adjuvant Opdivo, compared to neoadjuvant platinum-doublet chemotherapy and placebo followed by surgery and adjuvant placebo. The study consisted of 461 patients who were randomly assigned to receive either neoadjuvant Opdivo 360 mg with platinum-doublet chemotherapy every three weeks, or placebo and platinum-doublet chemotherapy every three weeks, until disease progression or unacceptable toxicity, for up to four cycles, followed by single-agent Opdivo 480 mg after surgery every four weeks or placebo every four weeks, until disease progression or unacceptable toxicity.

The primary endpoint was EFS determined by Blinded Independent Central Review (BICR), with secondary endpoints including pathologic complete response and major pathologic response determined by Blinded Independent Pathological Review (BIPR).

Results found that Opdivo reduced the risk of disease recurrence, progression, or death by 42%, with 25% of patients achieving pCR and a median follow-up of 25.4 months. Further, 18-month EFS was demonstrated in 70% of patients in the Opdivo arm, compared to 50% of patients in the chemotherapy and placebo arm.

BMS stated that Opdivo is associated with a number severe and fatal immune-mediated adverse events (AEs), including pneumonitis; colitis; hepatitis and hepatotoxicity; endocrinopathies; dermatologic AEs; nephritis and renal dysfunction; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryo-fetal toxicity. The most common AEs reported in the trial were anemia, constipation, nausea, fatigue, alopecia, and cough. The safety profile of this regimen was consistent with previously reported Opdivo studies in NSCLC and no new safety signals were identified.¹

According to Yale Medicine, 85% of all lung cancers are NSCLC. By the time of diagnosis, 40% of all cases will have spread beyond the lungs.²

“This milestone expands the role of Opdivo -based treatments and builds upon the foundation set by the FDA approval of neoadjuvant-only Opdivo plus chemotherapy in resectable NSCLC based on the CheckMate-816 trial,” said Wendy Short Bartie, SVP, US oncology and hematology, BMS, in a press release. “With this new Opdivo-based regimen, we are reinforcing our commitment to helping improve patient outcomes and expanding our thoracic portfolio in early-stage disease.”

References

1. U.S. Food and Drug Administration Approves Perioperative Treatment of Neoadjuvant Opdivo® (nivolumab) and Chemotherapy Followed by Surgery and Adjuvant Single-Agent Opdivo for Resectable Non-Small Cell Lung Cancer (NSCLC). BMS. October 3, 2024. Accessed October 4, 2024. https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Approves-Perioperative-Treatment-of-Neoadjuvant-Opdivo-nivolumab-and-Chemotherapy-Followed-by-Surgery-and-Adjuvant-Single-Agent-Opdivo-for-Resectable-Non-Small-Cell-Lung-Cancer-NSCLC/default.aspx

2. Non-Small Cell Lung Cancer. Yale Medicine. Accessed October 4, 2024. https://www.yalemedicine.org/conditions/non-small-cell-lung-cancer