Postoperative Nivolumab Does Not Improve DFS in Resected NSCLC

Key Takeaways

• Adjuvant nivolumab was not associated with a significant disease-free survival benefit compared with observation in patients with resected NSCLC who completed standard adjuvant therapy.
• No significant disease-free survival benefit was observed among patients with PD-L1 expression of at least 50%.
• Grade 3 to 5 treatment-related toxicities occurred in 25% of patients receiving nivolumab, including 2 treatment-related deaths.

Adjuvant nivolumab did not improve disease-free survival in patients with resected non–small cell lung cancer (NSCLC) who had completed standard adjuvant chemotherapy or radiotherapy in the phase 3 EA5142/ALCHEMIST trial. The study evaluated whether adjuvant nivolumab could improve disease-free survival and overall survival compared with observation following surgery and standard therapy.

EA5142 enrolled 935 patients, with 466 randomized to receive nivolumab and 469 randomized to observation. Eligible patients had resected NSCLC measuring at least 4 cm or lymph node–positive disease, EGFR/ALK wildtype status if nonsquamous histology was present, and completion of standard adjuvant therapy. Median age was 66 years in the nivolumab group and 67 years in the observation group. Participants were predominantly White, and 52% were male.

The phase 3, open-label trial randomized patients 1:1 to nivolumab or observation. Nivolumab was administered at 480 mg intravenously every 4 weeks for up to 1 year. Observation consisted of standard clinical and imaging follow-up. Median follow-up was 72.6 months.

Among all participants, median disease-free survival was 71.3 months with nivolumab and 68.8 months with observation, demonstrating no significant improvement with adjuvant nivolumab. Among patients with PD-L1 expression of at least 50%, median disease-free survival was 89.8 months with nivolumab and 78.5 months with observation, with no significant benefit observed. Overall survival was reported to be similar between the treatment groups.

Grade 3 to 5 treatment-related toxicities occurred in 25% of patients receiving nivolumab, including 2 treatment-related deaths.

The findings suggest that adjuvant nivolumab, given after surgery and standard therapy, does not further reduce the risk of cancer recurrence in patients with resected NSCLC. These results may influence the use of nivolumab in this setting and support continued investigation of alternative treatment strategies.

Limitations of the study included its open-label design, variable timing of enrollment after surgery, and limited racial and ethnic diversity among participants. Additional research is needed to optimize treatment strategies and sequencing in early-stage NSCLC.