In the phase III CANOPY-A trial reported in Journal of Clinical Oncology, Edward B. Garon, MD, and colleagues found that adjuvant therapy with the interleukin (IL)-1β pathway inhibitor canakinumab did not significantly improve disease-free survival vs placebo in patients with completely resected non–small cell lung cancer (NSCLC).
As stated by the investigators, “The IL-1β pathway has been linked with tumor development and progression, including in the Canakinumab Anti-Inflammatory Thrombosis Outcomes cardiovascular study, in which IL-1β pathway inhibition with canakinumab reduced lung cancer incidence and mortality in an exploratory analysis.”
Edward B. Garon, MD
Study Details
In the international double-blind trial, 1,382 patients with resected stage II–IIIA or IIIB (T > 5 cm, N2-positive) who had received adjuvant platinum-based chemotherapy were randomly assigned between April 2018 and December 2021 to receive canakinumab at 200 mg (n = 693) or placebo (n = 689) once every 3 weeks for 18 cycles. The primary endpoint was disease-free survival; overall survival was to be tested if the canakinumab group had significantly better disease-free survival.
Key Findings
Median disease-free survival was 35.0 months in the canakinumab group vs 29.7 months in the placebo group (hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.78–1.14, P = .258). No significant differences between the therapies were observed among evaluated subgroups.
Overall survival was not formally tested. Death occurred in 44 patients (6.3%) in the canakinumab group and 56 patients (8.1%) in the placebo group (HR = 0.72, 95% CI = 0.48–1.08).
Canakinumab IL-1β pathway inhibition resulted in decreased C-reactive protein and IL-6 levels, but these alterations were not associated with differences in outcomes between the treatment groups.
Two adverse events of any grade occurred in > 10% of patients, with both being less common in the canakinumab group: cough (11.4% vs 14.8%) and arthralgia (10.0% vs 12.0%). Grade ≥ 3 adverse events were reported in 20.8% of patients in the canakinumab group and 19.6% of the placebo group. Adverse events led to discontinuation of treatment in 4.3% and 4.1% of patients, respectively. Adverse events led to death in 5 (0.7%) vs 12 patients (1.7%); death was considered treatment-related in two patients in the placebo group.
The investigators concluded, “CANOPY-A did not show a disease-free survival benefit of adding canakinumab after surgery and adjuvant cisplatin-based chemotherapy in patients with resected, stage II–III NSCLC. No new safety signals were identified with canakinumab.”
Dr. Garon, of David Geffen School of Medicine at UCLA, 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.
