Canakinumab in combination with docetaxel compared with docetaxel alone for the treatment of advanced Non-Small cell lung cancer following Platinum-Based doublet chemotherapy and immunotherapy (CANOPY-2): A Multicenter, Randomized, Double-Blind, phase 3 trial
Mené sur 237 patients atteints d'un cancer du poumon non à petites cellules de stade IIIB/IV, cet essai multicentrique de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout de canakinumab au docétaxel après l'échec d'une chimiothérapie à base de sels de platine et d'une immunothérapie
Objectives: Canakinumab, an interleukin-1 beta inhibitor, previously showed reduced lung cancer incidence and mortality (CANTOS). Here, we compare the efficacy/safety of canakinumab versus placebo in patients with advanced non-small cell lung cancer (NSCLC), who had progressed after platinum-based doublet chemotherapy (PDC) and immunotherapy. Materials and methods: CANOPY-2, a randomized, double-blind, phase 3 trial, enrolled adult patients with stage IIIB/IV NSCLC, without EGFR or ALK alterations, who had received one prior PDC regimen and one prior programmed death-1/programmed death-ligand 1 inhibitor and experienced subsequent disease progression. Patients were randomized to canakinumab plus docetaxel or placebo plus docetaxel. Results: A total of 237 patients were randomly allocated: 120 (51 %) to canakinumab and 117 (49 %) to placebo, stratified by histology and prior lines of therapy. Three patients in the placebo arm did not receive study treatment. The trial did not meet its primary endpoint of overall survival: median 10.5 months (95 % confidence interval [CI], 8.1–12.4) for the canakinumab arm and 11.3 months (95 % CI, 8.5–13.8) for the placebo arm (hazard ratio, 1.06 [95 % CI, 0.76–1.48]; one-sided P-value = 0.633). AEs (any grade) were reported in 95 % of patients in the canakinumab group and in 98 % of patients in the placebo group. Grade 3–4 AEs were experienced by 62 % and 64 % of patients in the canakinumab and placebo groups, respectively, and grade 5 AEs were experienced by 8 % and 5 %. Prespecified, post-hoc, subgroup analyses showed that patients with undetected circulating tumor DNA (ctDNA) and/or lower levels (<10 mg/L) of C-reactive protein (CRP) achieved longer progression-free and overall survival than those with detected ctDNA or higher (≥10 mg/L) CRP levels. There was no association with treatment arm. Conclusion: Adding canakinumab to docetaxel did not provide additional benefit for patients with advanced NSCLC who had progressed after PDC and immunotherapy.
Lung Cancer 2024