Perioperative nivolumab boosts event-free survival in NSCLC

Perioperative treatment with chemotherapy plus nivolumab outperforms preoperative chemotherapy alone in participants with resectable non-small cell lung cancer (NSCLC), the first results of the CheckMate 77T trial demonstrated.

In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy previously resulted in significantly longer event-free survival (EFS) and a higher percentage of patients with a pathological complete response (pCR) than chemotherapy alone [1]. The subsequent phase 2 study CheckMate 816 (NCT02998528)  showed further improvement with a perioperative approach including adjuvant nivolumab [2]. The current phase 3 CheckMate 77T trial (NCT04025879) is the first study to explore the efficacy and safety of this perioperative approach in participants with resectable stage II–IIIB NSCLC. Dr Tina Cascone (MD Anderson Cancer Center, TX, USA) presented the results from the pre-specified interim analysis [3].

CheckMate 77T enrolled 416 participants with resectable NSCLC (stage IIA–IIIB, without EGFR mutation or ALK rearrangement) who had no prior systemic anti-cancer treatment. Participants were randomised 1:1 to perioperative nivolumab plus chemotherapy or placebo plus chemotherapy (4 cycles neoadjuvant therapy, followed by surgery and 1-year adjuvant therapy). Of all enrolled participants, 78% underwent surgery, 62–66% received adjuvant therapy and 60% completed adjuvant therapy.

At a median follow-up of 25 months, the trial met its primary endpoint, as EFS was in favour of the nivolumab-treated arm: not reached versus 18.4 months (HR 0.58; 95% CI 0.42–0.81; P=0.00025; see Figure). EFS rates at 18 months were 70% and 50% in the nivolumab and placebo arm, respectively. EFS benefit for nivolumab was observed across subgroups, including stratification by PD-L1 status. Also, pCR was improved in the nivolumab arm (25.3% vs 4.7%; odds ratio 6.64; 95% CI 3.40–12.97). Perioperative nivolumab increased EFS regardless of the pCR status. No new safety issues were observed.

Figure: EFS per blinded independent central review (BICR) with neoadjuvant nivolumab plus chemotherapy and adjuvant nivolumab versus chemotherapy plus placebo [3]



EFS, event-free survival. NIVO, nivolumab. PBO, placebo. HR, hazard ratio. Chemo, chemotherapy. CI, confidence interval.

Dr Cascone concluded: “These interim results support perioperative nivolumab as a potential new treatment option for patients with resectable NSCLC.” However, the study did not yet report whether there is an additional benefit of adjuvant nivolumab in patients who have a pCR after neoadjuvant nivolumab, as discussant Dr Marina Garassino (Instituto Nationale dei Tumori, Italy) remarked.

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   1. Provencio M, et al. N Eng J Med. 2023;389:504–513.
   2. Forde P, et al. N Engl J Med. 2022;386:1973–1985.
   3. Cascone T, et al. CheckMate 77T: Phase III study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage II–IIIb NSCLC. Abstract LBA1, ESMO 2023, 20–24 October, Madrid, Spain.

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Posted on 19 December, 202319 December, 2023