CONFERENCE UPDATE: ESMO 2023

Survival benefits of neoadjuvant nivolumab chemotherapy combination in patients with resectable NSCLC regardless of PD-L1 expression maintained in 3-year exploratory analysis from the CheckMate 816 trial

ONCOLOGY
29 Dec 2023

STUDY DESIGN

Results from the phase 3 CheckMate 816 study had found that neoadjuvant nivolumab plus chemotherapy (CTx) induced clinically significant and sustained benefits in the event-free survival (EFS) and overall survival (OS) of patients with resectable non-small cell lung cancer (NSCLC) compared to CTx-only.1 An exploratory subgroup analysis at 3 years was conducted to investigate the efficacy and safety outcomes of this combined neoadjuvant treatment among NSCLC patients by tumor programmed death-ligand 1 (PD-L1) expression (≥1% or <1%).1

During the phase 3 CheckMate 816 Study, adult patients with stage IB–III resectable NSCLC were randomized 1:1 to receive 360mg of nivolumab plus CTx once every 3 weeks or CTx only once every 3 weeks for 3 cycles.1 Both treatment groups consisted of similar proportions of patients with a tumor PD-L1 expression of ≥1% (nivolumab + CTx=89, CTx=89) and <1% (nivolumab + CTx=78, CTx=77).1

The endpoints of this exploratory analysis included event-free survival (EFS), overall survival (OS), pathologic complete response (pCR), major pathological response (MPR), surgical outcomes, and safety in patients with tumor PD-L1 ≥ 1% or < 1%.1 The minimum and median follow-ups were 32.9 months and 41.1 months, respectively.

Exploratory endpoints:
  • Selected endpoints were stratified by tumor PD-L1 expression and included EFS, OS, pCR, and surgical outcomes
  • Nivolumab + CTx exhibited a 63% risk-reduction in all-cause mortality (HR=0.37; 95% CI: 0.20-0.71) in patients with PD-L1 expression ≥1% compared with patients who received CTx only1
  • They also had a 54% risk-reduction in encountering negative disease events (HR=0.46; 95% CI: 0.28-0.77) and a higher pCR rate (difference=30.3%; 95% CI: 19.9-40.7) over the CTx only cohort1
  • When further targeting PD-L1 positive patients with stage II-IIIA disease, the addition of nivolumab retained favorable survival outcomes over the CTx only cohort (HR=0.43; 95% CI: 0.22-0.83)
  • In this population, the pCR (difference=29.8%; 95% CI: 19.0-40.7) and EFS (HR=0.49; 95% CI:0.29-0.83) results were also favorable1
  • The benefits of adding nivolumab was less pronounced in patients with tumor PD-L1 <1%, with only a 19% risk reduction in all-cause mortality (HR=0.81; 95% CI: 0.48-1.36)1
  • Similarly, the difference in pCR rate (14.1%; 95% CI: 4.8-24.0) and the risk-reduction in encountering negative disease events (HR=0.87; 95% CI: 0.57-1.35) were also less prominent in this population1
  • Patients who achieved pCR (n=43) had improved EFS (HR=0.15; 95% CI: 0.06-0.37) and OS (HR=0.12; 95% CI: 0.03-0.50) compared to those who did not (n=136) in the nivolumab + CTx cohort1
  • A numerically higher proportion of patients in the nivolumab + CTx cohort received lobectomy instead of pneumonectomy, regardless of their tumor PD-L1 expression (PD-L1 ≥1%: 79% vs. 17%, PD-L1 <1%: 81% vs. 11%)1
Safety:
  • Neoadjuvant nivolumab + CTx was found to be well-tolerated among patients, with a numerically higher rate of patients successfully undergoing definitive surgery compared to CTx alone, regardless of tumor PD-L1 expression (tumor PD-L1 ≥ 1%: 84% vs.74%; tumor PD-L1 <1%: 81% vs. 77%)1

 

“Results of this exploratory analysis reinforce the role of nivolumab plus chemotherapy as a standard neoadjuvant treatment for patients with resectable NSCLC, regardless of tumor PD-L1 expression.”

Dr. Mariano Provencio Pulla
Medical Oncology Department,
Puerta de Hierro University Hospital
Madrid, Spain

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