Addition of Canakinumab to First-Line Pembrolizumab Plus Chemotherapy Did Not Prolong Survival Outcomes Among Patients With Advanced/Metastatic Non-Small Cell Lung Cancer

According to results from the CANOPY-1 trial, the addition of canakinumab, a monoclonal anti-interleukin-1β (IL-1β) antibody, to pembrolizumab plus chemotherapy in the first-line setting did not prolong progression-free survival (PFS) or overall survival (OS) among patients with advanced or metastatic non-small cell lung cancer (NSCLC) who do not harbor ALK or EGFR mutations. 

Daniel S. W. Tan, MD, PhD, National Cancer Centre Singapore, and coauthors wrote, “IL-1β blockade may facilitate the antitumor activity of anti–PD-L1 treatment as a synergistic effect between both treatments has been observed in lung cancer preclinical models.” In the phase 3 CANTOS trial, evaluating canakinumab for the secondary prevention of major cardiovascular events among patients with atherosclerosis and a history of myocardial infarction, an exploratory analysis found “dose-dependent reductions in lung cancer incidence and mortality.”

In this phase 3, double-blind study, 643 patients were randomized to receive 200 mg of canakinumab once every 3 weeks (n = 320) or placebo (n = 323) in addition to 200 mg of pembrolizumab once every 3 weeks plus platinum-based doublet chemotherapy. The primary end points were PFS and OS. Secondary end points included safety and patient-reported outcomes. 

At a median follow-up of 6.5 months, median PFS was 6.8 months in the canakinumab arm and 6.8 months in the placebo arm (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.67 to 1.09; P = .102). Median OS was 20.8 months in the canakinumab arm and 20.2 months in the placebo arm (HR, 0.87; 95% CI, 0.70 to 1.10; P = .123) at a median follow-up of 21.2 months. 

No unexpected safety signals were observed in the canakinumab arm. Patients experienced clinically meaningful delays in deterioration of lung cancer symptoms including chest pain and coughing per LC13 and dyspnea per LC13 and C30. Grade ≤2 neutropenia and ALT increase were reported at a higher frequency in the canakinumab arm. Infection rates were comparable in both treatment arms and higher baseline C-reactive protein and IL-6 levels were associated with shorter PFS and OS.

JSCO Associate Editor Thomas E Stinchcombe, MD, Duke Cancer Center, Durham, North Carolina, stated, “Canakinumab did not improve outcomes in patients with metastatic NSCLC. A better understanding of the IL-1β pathway is needed in order to develop therapeutic agents that target this pathway.”

Source: 

Tan DSW, Felip E, De Castro G, et al. Canakinumab versus placebo in combination with first-line pembrolizumab plus chemotherapy for advanced non–small-cell lung cancer: Results from the CANOPY-1 trial. J Clin Oncol. Published online: December 1, 2023. doi:10.1200/JCO.23.00980