Neoadjuvant/adjuvant nivolumab is approved by the USFDA for resectable non-small cell lung cancer

On October 3, 2024, the Food and Drug Administration sanctioned nivolumab (Opdivo, Bristol Myers Squibb Company) in conjunction with platinum-doublet chemotherapy as neoadjuvant therapy, succeeded by single-agent nivolumab post-surgery as adjuvant therapy, for adults with resectable non-small cell lung cancer (NSCLC) characterized by tumors ≥ 4 cm and/or node positivity, and devoid of known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

The efficacy was assessed in CHECKMATE-77T (NCT04025879), a randomized, double-blind, placebo-controlled multicenter trial involving 461 patients with previously untreated and resectable non-small cell lung cancer (NSCLC) at Stage IIA to selected Stage IIIB (AJCC, 8th edition). Patients were randomized (1:1) to receive either nivolumab or placebo, in conjunction with platinum-based chemotherapy, administered every 3 weeks for a maximum of 4 cycles (neoadjuvant treatment), followed by either ongoing single-agent nivolumab or placebo every 4 weeks for up to 13 cycles (adjuvant treatment).

The primary efficacy outcome measure was event-free survival (EFS) assessed by blinded independent central review. The median event-free survival (EFS) was not attained (95% CI: 28.9, not estimable [NE]) in the nivolumab group, while it was 18.4 months (95% CI: 13.6, 28.1) in the chemotherapy group (hazard ratio 0.58 [95% CI: 0.43, 0.78]; p-value 0.00025). During the predetermined interim analysis, overall survival (OS) was not subjected to rigorous statistical significance testing; yet, a descriptive analysis indicated no adverse effects.

Adverse effects were comparable to those observed in other clinical trials, including nivolumab and chemotherapy. Among those administered neoadjuvant nivolumab, 5.3% were precluded from surgery due to adverse effects, in contrast to 3.5% in the placebo group. Furthermore, 4.5% of patients who underwent neoadjuvant treatment and surgery in the nivolumab group experienced surgical delays due to side effects, in contrast to 3.9% in the placebo group. Refer to the prescription instructions for further safety details.

The advised dosage of nivolumab is 360 mg every three weeks for neoadjuvant treatment and 480 mg every four weeks for adjuvant treatment. Nivolumab must be delivered before chemotherapy when given on the same day.

This evaluation was performed under Project Orbis, a program of the FDA Oncology Center of Excellence. Project Orbis offers a framework for the simultaneous submission and evaluation of oncology treatments among global collaborators. For this evaluation, the FDA partnered with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Israel's Ministry of Health (IMoH). The application evaluations are currently in progress at the other regulatory bodies.