TY - JOUR
T1 - 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)
T2 - A multicenter, randomized, double-blind, phase 3 trial
AU - Paz-Ares, Luis
AU - Goto, Yasushi
AU - Wan-Teck Lim, Darren
AU - Halmos, Balazs
AU - Chul Cho, Byoung
AU - Cobo, Manuel
AU - Luis González Larriba, José
AU - Zhou, Caicun
AU - Demedts, Ingel
AU - Atmaca, Akin
AU - Baka, Sofia
AU - Mookerjee, Bijoyesh
AU - Portella, Socorro
AU - Zhu, Zewen
AU - Wu, Jincheng
AU - Demanse, David
AU - Dharan, Bharani
AU - Reck, Martin
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/3
Y1 - 2024/3
N2 - 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 10.6 months (95 % confidence interval [CI], 8.2–12.4) 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. Clinical registration: NCT03626545.
AB - 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 10.6 months (95 % confidence interval [CI], 8.2–12.4) 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. Clinical registration: NCT03626545.
KW - Canakinumab
KW - CRP
KW - ctDNA
KW - Docetaxel
KW - Immunotherapy
KW - Non-small cell lung cancer
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U2 - 10.1016/j.lungcan.2023.107451
DO - 10.1016/j.lungcan.2023.107451
M3 - Article
C2 - 38354535
AN - SCOPUS:85185460342
SN - 0169-5002
VL - 189
JO - Lung Cancer
JF - Lung Cancer
M1 - 107451
ER -