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Adding nivolumab (Opdivo) to neoadjuvant chemotherapy followed by adjuvant treatment with the PD-1 inhibitor alone significantly increased event-free survival (EFS) for patients with resectable non-small cell lung cancer (NSCLC), the randomized CheckMate 77T trial showed.

EFS rates at 18 months reached 70.2% with the perioperative nivolumab strategy versus 50% with chemotherapy alone (HR 0.58, 97.36% CI 0.42-0.81), reported Tina Cascone, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues.

In addition, patients in the nivolumab group were more likely to achieve a pathological complete response (25.3% vs 4.7% in the chemotherapy group) and a major pathological response (35.4% vs 12.1%, respectively), according to the findings in the .

"The benefit of perioperative nivolumab over chemotherapy was evident with respect to event-free survival in patients with stage III disease, including those with single-station and multistation nodal involvement, who represented nearly two-thirds of the population in the trial. These findings are consistent with other reports of perioperative immunotherapy in patients with resectable NSCLC," they said.

Cascone and colleagues pointed out that nivolumab in combination with platinum-doublet chemotherapy is now a standard neoadjuvant treatment for eligible patients with resectable NSCLC based on results from the CheckMate 816 trial.

Moreover, adjuvant immunotherapy has shown benefit with respect to disease-free survival in patients with resectable NSCLC, leading the authors to suggest a perioperative approach could further improve clinical outcomes.

In an editorial accompanying the study, Marina Chiara Garassino, MD, of the University of Chicago, and Valter Torri, MD, of the Istituto di Ricovero e Cura a Carattere Scientifico in Milan, pointed out that CheckMate 77T is the fifth phase III trial demonstrating a benefit with adding perioperative immunotherapy to neoadjuvant chemotherapy for resectable lung cancer.

The other four include evaluations of durvalumab (Imfinzi) in the AEGEAN trial, toripalimab (Loqtorzi) in Neotorch, tislelizumab (Tevimbra) in RATIONALE-315, and pembrolizumab (Keytruda) in KEYNOTE-671 -- which is now the standard of care in this setting after demonstrating a significant improvement in overall survival and receiving FDA approval in resectable NSCLC.

Thus, "with all these options, how can a physician choose an approach tomorrow morning?" Garassino and Torri asked.

They said the results from these studies suggest the drugs could be interchangeable, and recommended that physicians should consider their interchangeability "on the basis of such factors as drug availability, cost, and individual preference."

As to whether a perioperative strategy is better than approved neoadjuvant-only approaches, that is less clear, the editorialists suggested.

In the current study, a post hoc analysis by adjuvant treatment status showed that EFS from definitive surgery favored perioperative nivolumab over chemotherapy in patients who had received adjuvant treatment (HR 0.43, 95% CI 0.28-0.67), as well as among the patients who could not receive adjuvant treatment (HR 0.44, 95% CI 0.22-0.87).

"Although perioperative approaches, including the strategy that was used in CheckMate 77T, have shown a benefit, they may not be superior to neoadjuvant-only strategies," Garassino and Torri commented. "Until clearer evidence emerges, personalized decision making on the basis of patient preference is recommended."

randomized 461 patients with resectable stages IIA-IIIB NSCLC to neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo every 3 weeks for 4 cycles, followed by surgery and then adjuvant nivolumab or placebo every 4 weeks for 1 year.

Patient characteristics were balanced between the treatment groups and largely representative of the overall population of NSCLC patients, except for Black patients, who were underrepresented (and which the authors acknowledged was a limitation to the study).

Adverse events (AEs) were reported in 97.4% of patients in the nivolumab group and in 97.8% in the chemotherapy-only group. Grade 3/4 treatment-related AEs occurred in 32.5% and 25.2% of the patients, respectively.

Overall, treatment-related AEs leading to drug discontinuation occurred in 19.3% of the patients in the nivolumab group and in 7.4% of those in the chemotherapy group.

Subgroup analysis by PD-L1 status showed greater benefit for patients with a tumor PD-L1 expression of 1% or higher:

• PD-L1 ≥1%: HR 0.52 (95% CI 0.35-0.78)
• PD-L1 <1%: HR 0.73 (95% CI 0.47-1.15)

"In an exploratory landmark analysis, event-free survival from definitive surgery appeared to favor nivolumab over chemotherapy both in patients who had a pathological complete response and in those who did not," noted Cascone and colleagues.

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