[MP Test] Neoadjuvant cycles do not alter perioperative nivolumab benefit in resectable NSCLC

Treatment with nivolumab plus chemotherapy before surgery followed by nivolumab after surgery yields superior outcomes for patients with resectable nonsmall cell lung cancer (NSCLC) as compared with placebo plus chemotherapy, regardless of the number of completed neoadjuvant cycles, according to an exploratory analysis of the CHECKMATE 77T trial.

In the cohort of patients who completed all 4 cycles of neoadjuvant treatment, the rate of pathological complete response (pCR) was 26.7 percent in the nivolumab arm versus 5.4 percent in the placebo arm (difference, 21.3 percent; 95 percent confidence interval [CI], 14.3–28.4). "Among those who underwent resection in the same cohort, the pCR rate was 25.7 percent [95 percent CI, 17.4–33.9] higher in the nivolumab arm," reported lead researcher Prof Mark Awad of Dana-Farber Cancer Institute in Boston, Massachusetts, US. [Awad M, et al, ELCC 2024, abstract LBA2]

"Similarly, the nivolumab arm showed improved pCR compared with the placebo arm in the cohort of patients who completed fewer than 4 cycles of neoadjuvant treatment," Awad added. The pCR rates were 18.4 percent versus 0.0 percent overall and 35.0 percent vs 0 percent among patients who underwent resection.

Results for major pathological response (MPR) followed the same pattern as those for pCR. MPR rates in the nivolumab arm were higher by 24.6 percent overall and by 29.5 percent among patients who underwent resection in the 4 cycles cohort, and by 21.1 percent and 40.0 percent, respectively, in the <4 cycles cohort.

In terms of event-free survival (EFS), perioperative nivolumab likewise conferred a meaningful benefit compared with placebo. The median EFS was not reached in the nivolumab arm versus 19.8 months in the placebo arm in the 4 cycles cohort (hazard ratio [HR], 0.57; 95 percent CI, 0.42–­0.79), and not reached versus 7.8 months, respectively, in the <4 cycles cohort (HR, 0.51; 95 percent CI, 0.23–1.11).

The 1-year EFS rates were 76 percent with nivolumab and 61 percent with placebo in the 4 cycles cohort and 62 percent and 36 percent, respectively, in the <4 cycles cohort.

TTDM data

“In all randomized patients, we see a significant improvement in time to death or distant metastasis [TTDM] among patients who received perioperative nivolumab compared to placebo [1-year TTDM rate: 81 percent vs 71 percent; median TTDM: not reached vs 38.8 months; HR, 0.62; 95 percent CI, 0.44–0.85],” Awad noted.

“If we break this down into patients who received 4 cycles versus <4 cycles of neoadjuvant therapy, we see favourable HRs for the groups of patients who received perioperative nivolumab [0.61 and 0.46, respectively],” he continued.

Looking at TTDM by pCR and MPR status, Awad noted impressive outcomes. TTDM rates were favourable for patients who achieved pCR in the nivolumab arm as well as for the few who achieved pCR in the placebo arm, he added. The same held true for TTDM according to MPR.

Meanwhile, for patients who did not achieve pCR or MPR, a trend toward better TTDM was observed in the nivolumab arm.

Safety data

“Most patients who could receive adjuvant nivolumab after neoadjuvant nivolumab plus chemo received the full 13 adjuvant cycles and had a manageable safety profile,” Awad pointed out.

“The safety and toxicities that were observed in the adjuvant treatment portion were comparable among patients who received 4 or fewer than 4 cycles of neoadjuvant therapy,” he continued.

Any grade adverse events (AEs) occurred in 87 percent of patients with nivolumab versus 80 percent with placebo in the 4 cycles cohort and 91 percent versus 71 percent, respectively, in the <4 cycles cohort. AEs led to treatment discontinuation in 14 percent versus 4 percent and 9 percent versus 14 percent in the respective cohorts. The rates of serious AEs in the nivolumab versus placebo arms were 22 percent versus 16 percent in the 4 cycles cohort and 18 percent versus 0 percent in the <4 cycles cohort, respectively.

“These results further support perioperative nivolumab as a potential new treatment option, which builds on the standard of care neoadjuvant nivolumab plus chemo, for patients with resectable NSCLC,” Awad concluded.

CHECKMATE 77T included adult patients with suspected or histologically confirmed stage IIA to IIIB NSCLC that was considered resectable. These patients were randomly assigned to receive (1) 360 mg of nivolumab plus chemotherapy once every 3 weeks for up to 4 cycles as neoadjuvant treatment or (2) placebo plus chemotherapy once every 3 weeks for up to 4 cycles.

Patients were scheduled to undergo surgery within 6 weeks of the completion of neoadjuvant therapy following radiological restaging. Adjuvant nivolumab was administered at 480 mg once every 4 weeks for up to 1 year in the nivolumab arm, while adjuvant placebo was given once every 4 weeks for up to 1 year in the control arm. The median follow-up was 25.4 months.