As reported in the Journal of Clinical Oncology by Tan et al, the phase III CANOPY-1 trial has shown no survival benefits with the addition of canakinumab to first-line pembrolizumab plus chemotherapy in patients with advanced/metastatic non–small cell lung cancer (NSCLC) without EGFR or ALK mutations.
As noted by the investigators, canakinumab, a human monoclonal anti–interleukin (IL)-1β antibody, may enhance the activity of PD-L1 inhibitors and chemotherapy via inhibition of protumor inflammation.
Study Details
In the global double-blind trial, 643 patients were randomly assigned between June 2019 and January 2020 to receive canakinumab at 200 mg subcutaneously once every 3 weeks (n = 320) or placebo (n = 323) in addition to pembrolizumab at 200 mg every 3 weeks (up to 35 doses) and four cycles of a platinum-based doublet. The doublet regimens were either carboplatin at AUC 5 plus paclitaxel at 200 mg/m2 or nab-paclitaxel at 100 mg/m2 for squamous tumors, or carboplatin at AUC 5 or cisplatin at 75 mg/m2 plus pemetrexed at 500 mg/m2 for nonsquamous tumors, with maintenance pemetrexed permitted.
Treatment was continued until disease progression or unacceptable toxicity. The primary endpoints of the trial were investigator-assessed progression-free survival and overall survival.
Survival Outcomes
At the final cutoff date for progression-free survival analysis, median follow-up was 6.5 months (range = 4.0–10.8 months). Median progression-free survival was 6.8 months (95% CI = 5.6–7.8 months) in the canakinumab group vs 6.8 months (95% CI = 5.5–6.9 months) in the control group (hazard ratio [HR] for canakinumab vs control group = 0.85, 95% CI = 0.67–1.09, P = .102).
At the final cutoff date for overall survival analysis, median follow-up was 21.2 months (range = 18.8–25.5 months). Median overall survival was 20.8 months (95% CI = 16.3 months to not estimable) in the canakinumab group vs 20.2 months (95% CI = 16.2–22.4 months) in the control group (HR = 0.87, 95% CI = 0.70–1.10, P = .123). Rates at 12 and 24 months were 66.14% vs 63.47% and 46.01% vs 40.01%, respectively.
Objective response rates were 45.6% (95% CI = 40.1%–51.3%) in the canakinumab group vs 45.5% (95% CI = 40.0%–51.1%) in the control group. Median response duration was 14.3 months (95% CI = 10.40 months to not estimable) vs 13.6 months (95% CI = 10.30 months to not estimable).
Among all patients, higher baseline C-reactive protein and IL-6 levels were associated with poorer progression-free survival and overall survival.
Patients in the canakinumab group had clinically meaningful delays in deterioration of lung cancer symptoms, including chest pain (time to definitive 10-point deterioration [TTDD] = not reached vs 22.1 months), coughing (TTDD = not reached vs 23.1 months), and dyspnea (TTDD = 19.6 vs 11.5 months) on the EORTC Quality of Life Questionnaire lung cancer–specific module (QLQ-LC13).
Adverse Events
Grade 3 or 4 treatment-related adverse events occurred in 57.2% of patients in the canakinumab group vs 51.9% of those in the control group; grade 5 treatment-related adverse events occurred in 3.8% vs 5.0%. Treatment-related serious adverse events were reported in 32.2% vs 26.4% of patients.
Adverse events led to treatment discontinuation related to any drug in 20.3% vs 15.2% of patients, and to discontinuation of canakinumab or placebo in 6.3% vs 4.7%. Irrespective of causality attribution, grade 3 or 4 infection was reported in 15.0% vs 12.4% of patients and grade 5 infection in 5.6% vs 5.3%; grade 3 or 4 neutropenia occurred in 24.4% vs 16.8%; and grade 3 or 4 alanine aminotransferase increase was reported in 4.7% vs 3.1%.
The investigators concluded, “The addition of canakinumab to first-line pembrolizumab and chemotherapy did not prolong progression-free survival or overall survival in patients with NSCLC.”
Bruce E. Johnson, MD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Novartis Pharmaceuticals Corporation. For full disclosures of the study authors, visit ascopubs.org.
