Statistically Significant EFS Boost Observed With Nivolumab/Chemo for Resectable NSCLC

Results of the phase 3 CheckMate 816 trial (NCT02998528) showed a statistically significant and clinically meaningful improvement in event-free survival (EFS) with neoadjuvant nivolumab (Opdivo) plus chemotherapy vs chemotherapy alone for patients with resectable non–small cell lung cancer (NSCLC), representing a new standard of care in this setting.

The hazard ratio for the EFS benefit observed with neoadjuvant nivolumab and chemotherapy vs chemotherapy alone was 0.63 (97.38% CI, 0.43-0.91), according to a presentation given during the American Association for Cancer Research (AACR) 2022 Annual Meeting.

“Event-free survival benefit favored nivolumab plus chemotherapy in most subgroups. Preliminary overall survival analysis showed a trend of improvement with nivolumab plus chemotherapy versus chemotherapy alone with a hazard ratio of 0.57 [99.67% CI, 0.30-1.07]. The study continues to mature with a longer follow up,” Nicolas Girard, MD, professor of respiratory medicine at Versailles Saint Quentin University, and head of Curie-Montsouris Thorax Institute, Institut Curie, at the meeting.

CheckMate 816 aims to compare nivolumab plus chemotherapy and chemotherapy alone and describe the safety and effectiveness of nivolumab plus ipilimumab for treatment of resectable NSCLC.

The randomized, open-label, phase 3 trial enrolled an overall sample size of 358 patients with early stage IB-IIIA, operable NSCLC, a lung capacity capable of tolerating the proposed lung surgery, an ECOG performance status of 0 or 1, and available tissue of primary lung tumor.

Patients were randomized 1:1 to receive either nivolumab at 360 mg and chemotherapy for 3 cycles or just chemotherapy alone. The majority of the patients enrolled were men with a median age in the nivolumab plus chemotherapy arm of 64.

Of the 358 patients randomized in CheckMate 816, 94% completed the neoadjuvant treatment. In the experimental arm, 83% of patients (n = 149) had definitive surgery while 75% (n = 135) in the chemotherapy arm did. Additionally, 20% of patients in the experimental arm received adjuvant therapy (n = 35) while 32% did in the control arm (n = 56).

The dual primary end points of the study include EFS and pathological complete response at the time of surgery. Secondary end points include overall survival, major pathological response at the time of surgery, and time to death or distant metastases.

The study met its primary end point of pathological complete response at a median follow-up of 29.5 months. Median EFS was 31.6 months in the nivolumab plus chemotherapy arm and 20.8 months in the control arm. The 1-year EFS was 76% in the experimental arm and 63% in the control while the 2-year EFS was 64% versus 45%. EFS was consistently approved across most subgroups observed in the trial.

These findings revealed a statistically significant and clinically meaningful improvement in EFS to be shown in patients given nivolumab plus chemotherapy, including in patients who have a partial complete response.

Overall survival was also tested in this study but did not cross predefined statistical boundaries. This is expected given the small number of OS events, but future research should help experts learn more.

In regard to safety, adverse events (AEs) of any grade occurred in 93% of patients in the nivolumab plus chemotherapy arm and in 97% of those who received chemotherapy alone. Grade 3 or 4 AEs occurred in 41% in the experimental arm versus 44% in the control arm. Additionally, treatment-related AEs of any grade led to discontinuation in 10% of patients given nivolumab and chemotherapy as well as 10% of those given chemotherapy alone.

There were 2 patients in the nivolumab plus chemotherapy arm who reported grade 5 surgery-related AEs consisting of pulmonary embolism and aortic rupture, but they were deemed to be unrelated to the study

Neoadjuvant nivolumab plus chemotherapy demonstrated a safety profile which was consistent with previous reports and did not change the feasibility of surgery when compared to chemotherapy alone.

“CheckMate 816 is the first phase 3 study with a neoadjuvant immunotherapy-based combination for resectable NSCLC to show improved event-free survival and partial complete response, along with promising overall survival results. These results support neoadjuvant nivolumab in combination with chemotherapy as a standard of care for patients with resectable NSCLC,” Girard.

Reference

Girard N, Spicer J, Provencio M, et al. Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as neoadjuvant treatment for resectable (IB-IIIA) non-small cell lung cancer (NSCLC): Event-free survival (EFS) results from the phase 3 CheckMate 816 trial.Presented at: 2022 AACR Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CT012.