FDA Approves Nivolumab for the Treatment of Adult Patients With Resectable NSCLC

Updated: October 4, 2024 at 11:02AM

The FDA has approved nivolumab (Opdivo; Bristol Myers Squibb) for the treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) with no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, for neoadjuvant treatment in combination with platinum-doublet chemotherapy, followed by single-agent nivolumab as adjuvant treatment after surgery (or perioperative therapy). The approval comes after results from the phase 3 CheckMate-77T trial (NCT04025879).¹

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Previously, nivolumab was approved by the FDA for the treatment of adult patients with resectable NSCLC in the neoadjuvant setting when in combination with platinum-doublet chemotherapy. It also has indications in the neoadjuvant, adjuvant, or perioperative settings in lung cancer, melanoma, bladder cancer, and esophageal or gastroesophageal junction cancer. Nivolumab is now the only PD-1 inhibitor to demonstrate statistically significant and clinically meaningful benefits in NSCLC compared with chemotherapy in both a neoadjuvant-only regimen and as part of a perioperative regimen.¹

CheckMate-77T (NCT04025879) is a randomized, multicenter, double-blind phase 3 trial that evaluated neoadjuvant nivolumab with platinum-doublet chemotherapy followed by surgery and single-agent adjuvant nivolumab, compared with neoadjuvant platinum-doublet chemotherapy plus placebo followed by surgery and adjuvant placebo in patients with resectable NSCLC. A total of 461 patients were enrolled and randomly assigned to receive either neoadjuvant nivolumab (360 mg) in combination with platinum-doublet chemotherapy, or placebo and platinum-doublet chemotherapy every 3 weeks, until disease progression or unacceptable toxicity. These regimens were administered for up to 4 cycles, then followed by either single-agent nivolumab (480 mg) or placebo after surgery every 4 weeks, until disease progression or unacceptable toxicity for up to 13 cycles.^1,2

The primary end point for CheckMate-77T was event-free survival (EFS), which was assessed from randomization and up to 44 months. Secondary end points included overall survival (OS; measured from randomization and any-cause death), pathologic complete response (pCR) rate, major pathological response rate (measured from randomization and up to 44 months), as well as number of adverse events (AEs) and serious AEs (SAEs; measured up to 28 months).^1,2

According to the results, the risk of disease recurrence, progression, or death was reduced by approximately 42% (EFS HR 0.58; 95% CI: 0.43-0.78; P = .00025) at a median follow-up of 25.4 months in patients assigned to the nivolumab group, compared with the placebo arm. Additionally, 18-month EFS was observed in about 70% of patients in the nivolumab arm, compared with 50% of those in the placebo arm. The investigators also observed about 25% of patients in the nivolumab group who achieved pCR, whereas 4.7% achieved pCR in the opposing group (estimated treatment difference of 20.5%; 95% CI,14.3-26.6).^1,3

“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 of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, in a news 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 pathologic response in 1 in 4 patients.”¹

In the CheckMate-77T trial, the most common AEs in those receiving nivolumab with chemotherapy were anemia (39.5%), constipation (32.0%), nausea (28.9%), fatigue (28.1%), alopecia (25.9%), and cough (21.9%). Further, 12 patients (5.3%) treated with nivolumab who received neoadjuvant treatment, did not receive surgery because of adverse reactions, such as cerebrovascular accident (n = 2), pneumonia (n = 2), colitis or diarrhea (n = 2), acute coronary syndrome (n = 1), myocarditis (n = 1), hemoptysis (n = 1), pneumonitis (n = 1). COVID-19 (n = 1), and myositis (n = 1). SAEs occurred in about 22% of patients who received single-agent nivolumab as adjuvant treatment, with the most frequent being pneumonitis/ILD (2.8%).^1,3

“This milestone expands the role of [nivolumab]-based treatments and builds upon the foundation set by the FDA approval of neoadjuvant-only [nivolumab] plus chemotherapy in resectable NSCLC based on the CheckMate-816 trial,” said Wendy Short Bartie, senior vice president of US Oncology and Hematology at Bristol Myers Squibb, in the news release.¹

REFERENCES

1. Bristol Myers Squibb. 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). News release. October 3, 2024. Accessed October 4, 2024. https://news.bms.com/news/corporate-financial/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. A Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Removal and Adjuvant Treatment With Nivolumab or Placebo for Participants With Surgically Removable Early Stage Non-small Cell Lung Cancer. ClinicalTrials.gov identifier: NCT04025879. Updated July 23, 2024. Accessed October 4, 2024. https://clinicaltrials.gov/study/NCT04025879

3. Cascone T, Awad MM, Spicer JD, et al. Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med. 2024;390(19):1756-1769. doi:10.1056/NEJMoa2311926