Nivolumab plus chemo offers prolonged survival in resectable NSCLC

Patients with resectable nonsmall cell lung cancer (NSCLC) enjoy sustained survival from neoadjuvant nivolumab when added to chemotherapy compared with chemotherapy alone, as seen in the 4-year analysis from the phase III CheckMate 816 study.

“These 4-year results from CheckMate 816 provide the first understanding of the long-term benefits of neoadjuvant immunotherapy plus chemotherapy and reinforce nivolumab plus chemotherapy as a standard of care for patients with resectable NSCLC,” said lead author Dr Jonathan Spicer from McGill University Health Centre in Montreal, Canada.

Additionally, these data set the benchmark for assessing the benefits of other perioperative immunotherapy-based treatments, according to the investigators.

In CheckMate 816, Spicer and his team randomized adults with stage IB‒IIIA resectable NSCLC, ECOG PS ≤1, and no known EGFR/ALK alterations to receive either nivolumab 360 mg plus chemotherapy Q3W (n=179) or chemotherapy alone Q3W (n=179) for three cycles, followed by surgery.

The primary endpoints were event-free survival (EFS) and pathologic complete response (pCR; both per blinded independent review), while the secondary endpoint was overall survival (OS). The investigators also performed exploratory analyses, which included efficacy by pCR status and extent of resection.

Survival benefits

Database lock was on 23 February 2024. During a median follow-up of 57.6 months, nivolumab plus chemotherapy provided sustained improvements in EFS relative to chemotherapy alone (median, 43.8 vs 18.4 months; hazard ratio [HR], 0.66, 95 percent confidence interval [CI], 0.49‒0.90). EFS rates at 4 years for the two regimens were 49 percent and 38 percent, respectively. [ASCO 2024, abstract LBA8010]

Furthermore, EFS rates remained in favour of nivolumab plus chemotherapy regardless of whether patients underwent lobectomy or pneumonectomy, with 56‒57 percent of patients showing no disease recurrence at 4 years compared with 40‒43 percent with chemotherapy alone.

OS also showed continued improvement with nivolumab plus chemotherapy (HR, 0.71, 98.36 percent CI, 0.47‒1.07; p=0.0451; median OS was not reached in both arms, and the significance boundary was not met at the interim analysis). A 13-percent OS improvement was sustained over time for nivolumab plus chemotherapy compared with chemotherapy alone (4-year OS rates: 71 percent vs 58 percent).

Notably, patients in the combined treatment with pCR showed sustained OS improvement relative to those who did not achieve pCR (HR, 0.08, 95 percent CI, 0.02‒0.34; 4-year OS rates: 95 percent vs 63 percent). This trend also occurred in the monotherapy arm, but only a few patients achieved pCR (n=4).

“[N]eoadjuvant nivolumab plus chemotherapy demonstrated durable, long-term EFS benefit and a clinically important OS improvement trend versus chemotherapy [alone],” Spicer said.

No new safety signals were seen in this updated analysis, and the safety profile of the combined treatment remained consistent with previous findings, according to the investigators.

“Additional survival analyses in patient subgroups and by ctDNA levels will be presented [in the next update],” Spicer said.

The CheckMate 816 study established neoadjuvant nivolumab plus chemotherapy as a standard of care for eligible patients with resectable NSCLC, according to the investigators. The current study was funded by Bristol Myers Squibb.