European Commission Approves Perioperative Nivolumab and Chemotherapy for Resectable PD-L1+ NSCLC

The European Commission has approved neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by surgery and adjuvant nivolumab for the treatment of patients with resectable, high-risk non–small cell lung cancer (NSCLC) whose tumors have PD-L1 expression of 1% or greater.¹

The decision is based on data from the phase 3 CheckMate 77T trial (NCT04025879) study, which showed a 42% reduction in the risk of disease recurrence, progression, or death with neoadjuvant nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab alone, vs neoadjuvant platinum-doublet chemotherapy and placebo followed by surgery and adjuvant placebo in patients with resectable NSCLC (HR for event-free survival [EFS], 0.58; 95% CI, 0.43-0.78; P = .00025).

The 24-month EFS rate was 65% in the nivolumab arm compared with 44% in the placebo arm. The perioperative nivolumab regimen also led to clinically meaningful improvements in the secondary efficacy end points of pathologic complete response (pCR) and major pathologic response (MPR).

Additionally, the safety profile of the perioperative regimen was comparable to prior data reported in NSCLC, and no new safety signals were seen.

“This approval brings another perioperative immunotherapy treatment option for select patients with resectable NSCLC in the European Union, helping address an ongoing need for interventions that can meaningfully reduce the risk of cancer returning after initial therapy,” Dana Walker, MD, MSCE, vice president, [nivolumab] global program lead, Bristol Myers Squibb, stated in a news release. “With this approval, [nivolumab] with chemotherapy followed by adjuvant [nivolumab] has the potential to change the course of certain patients’ disease by significantly reducing the risk of cancer recurrence and improving long-term outcomes earlier in the treatment journey.”

In October 2024, the FDA approved nivolumab for use in combination with platinum-doublet chemotherapy as neoadjuvant treatment, followed by nivolumab monotherapy as adjuvant therapy, for patients with resectable (tumors ≥ 4 cm and/or node positive) NSCLC and no known EGFR mutations or ALK rearrangements.²

The regulatory decision was also based on findings from CheckMate 77T. CheckMate 77T was a double-blind study that enrolled patients with newly diagnosed resectable stage IIA to IIIB NSCLC per AJCC 8th Edition staging criteria.³ Eligibility criteria mandated an ECOG performance status of 0 or 1 and no EGFR mutations or known ALK translocations.

Eligible patients were randomly assigned 1:1 to receive nivolumab at a dose of 360 mg or placebo every 3 weeks, both in combination with chemotherapy every 3 weeks for up to 4 cycles. Patients in both arms underwent surgery followed by adjuvant nivolumab at a dose of 480 mg every 4 weeks or placebo at the same dosing schedule, for up to 13 cycles.

The primary end point was EFS by blinded independent central review. Secondary end points included pCR and MPR rates by blinded independent pathologic review, as well as overall survival and safety.

The latest analysis, which was presented at the 2024 ESMO Congress with an additional 7.9 months of median follow-up, demonstrated that patients who received perioperative nivolumab (n = 229) achieved a median EFS of 40.1 months (95% CI, 33.7-not reached) vs 17.0 months (95% CI, 13.6-28.1) in patients who received placebo (n = 232; HR, 0.59; 95% CI, 0.45-0.79).³ The 12-month EFS rates were 73% (95% CI, 67%-79%) and 59% (95% CI, 52%-65%), and the 24-month rates were 65% (95% CI, 58%-71%) and 44% (95% CI, 38%-51%), respectively.

Additionally, patients who experienced a pCR experienced prolonged EFS with nivolumab (n = 58) vs placebo (n = 11; HR, 0.59; 95% CI, 0.12-2.91). Notably, patients who did not achieve pCR on nivolumab (n = 98) also experienced an EFS benefit vs those who received placebo (n = 148; HR, 0.75; 95% CI, 0.51-1.09).

References

1. Bristol Myers Squibb receives European Commission approval for perioperative regimen of neoadjuvant Opdivo (nivolumab) and chemotherapy followed by adjuvant Opdivo for resectable, high-risk non-small cell lung cancer with PD-L1 expression ≥1%. News release. Bristol Myers Squibb. May 16, 2025. Accessed May 16, 2025. https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Receives-European-Commission-Approval-for-Perioperative-Regimen-of-Neoadjuvant-Opdivo-nivolumab-and-Chemotherapy-Followed-by-Adjuvant-Opdivo-for-Resectable-High-Risk-Non-Small-Cell-Lung-Cancer-with-PD-L1-Expression-1/default.aspx
2. FDA approves neoadjuvant/adjuvant nivolumab for resectable non-small cell lung cancer. FDA. October 3, 2024. Accessed May 16, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-nivolumab-resectable-non-small-cell-lung-cancer
3. Pulla MP, Awad MM, Cascone T, et al. Perioperative nivolumab (NIVO) vs placebo (PBO) in patients (pts) with resectable NSCLC: clinical update from the phase 3 CheckMate 77T study. Ann Oncol. 2024;35(suppl 2):S1239-S1240. doi:10.1016/j.annonc.2024.08.2291