PMID- 37788412 OWN - NLM STAT- MEDLINE DCOM- 20240108 LR - 20240108 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 42 IP - 2 DP - 2024 Jan 10 TI - Canakinumab as Adjuvant Therapy in Patients With Completely Resected Non-Small-Cell Lung Cancer: Results From the CANOPY-A Double-Blind, Randomized Clinical Trial. PG - 180-191 LID - 10.1200/JCO.23.00910 [doi] AB - PURPOSE: Effective treatments for resectable non-small-cell lung cancer (NSCLC) are limited and relapse rates are high. The interleukin (IL)-1beta pathway has been linked with tumor development and progression, including in the Canakinumab Anti-Inflammatory Thrombosis Outcomes cardiovascular study in which IL-1beta pathway inhibition with canakinumab reduced lung cancer incidence and mortality in an exploratory analysis. METHODS: CANOPY-A (ClinicalTrials.gov identifier: NCT03447769) is a phase III, randomized, double-blind, multicenter study of canakinumab versus placebo for adult patients with stage II-IIIA or IIIB (T >5 cm, N2-positives II-IIIB; American Joint Committee on Cancer/Union for International Cancer Control version 8), completely resected NSCLC who had received adjuvant cisplatin-based chemotherapy. The primary end point was disease-free survival (DFS) and the key secondary end point was overall survival (OS). RESULTS: In total, 1,382 patients were randomized to 200 mg canakinumab (n = 693) or placebo (n = 689) once every 3 weeks for 18 cycles. Grade >/=3 adverse events (AEs) were reported in 20.8% and 19.6% of patients receiving canakinumab and placebo, respectively; AEs led to discontinuation in 4.3% and 4.1% of patients in these groups, respectively. This study did not meet its primary end point. Median DFS was 35.0 months (canakinumab arm) and 29.7 months (placebo arm; hazard ratio, 0.94; 95% CI, 0.78 to 1.14; one-sided P = .258). DFS subgroup analyses did not show any meaningful differences between arms. As expected, because of canakinumab-driven IL-1beta pathway inhibition, C-reactive protein and IL-6 levels decreased in the canakinumab arm versus placebo arm, but had no correlation with differential clinical outcomes. OS was not formally tested as DFS was not statistically significant. CONCLUSION: CANOPY-A did not show a DFS 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. FAU - Garon, Edward B AU - Garon EB AUID- ORCID: 0000-0001-7077-8801 AD - David Geffen School of Medicine at UCLA/TRIO-US/TRIO-Global Network, Los Angeles, CA. FAU - Lu, Shun AU - Lu S AUID- ORCID: 0000-0001-8833-7262 AD - Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. FAU - Goto, Yasushi AU - Goto Y AUID- ORCID: 0000-0002-7437-5054 AD - National Cancer Center, Tokyo, Japan. FAU - De Marchi, Pedro AU - De Marchi P AUID- ORCID: 0000-0001-5259-0215 AD - Oncoclinicas, Rio de Janeiro, Brazil. FAU - Paz-Ares, Luis AU - Paz-Ares L AUID- ORCID: 0000-0002-1947-3364 AD - University Hospital 12 de Octubre, CNIO-H120 Lung Cancer Unit, Completense University and Ciberonc, Madrid, Spain. FAU - Spigel, David R AU - Spigel DR AUID- ORCID: 0000-0003-3215-9465 AD - Sarah Cannon Research Institute, Nashville, TN. FAU - Thomas, Michael AU - Thomas M AUID- ORCID: 0000-0001-9511-055X AD - Thoraxklinik and National Center for Tumor Diseases at Heidelberg University Hospital, Translational Lung Research Center Heidelberg (TLRH-C), German Center for Lung Research (DZL), Heidelberg, Germany. FAU - Yang, James Chih-Hsin AU - Yang JC AUID- ORCID: 0000-0002-5586-5138 AD - National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan. FAU - Ardizzoni, Andrea AU - Ardizzoni A AD - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. FAU - Barlesi, Fabrice AU - Barlesi F AD - Medical Oncology Department, Gustave Roussy, Villejuif, France. AD - Faculte de Medecine, Universite Paris-Saclay, Bicetre, France. FAU - Orlov, Sergey AU - Orlov S AUID- ORCID: 0000-0001-6080-8042 AD - Saint Petersburg Electrotechnical University, Saint Petersburg, Russia. FAU - Yoshioka, Hiroshige AU - Yoshioka H AUID- ORCID: 0000-0001-7724-0481 AD - Department of Thoracic Oncology, Kansai Medical University, Hirakata, Japan. FAU - Mountzios, Giannis AU - Mountzios G AD - Fourth Oncology Department and Clinical Trials Unit, Henry Dunant Hospital Center, Athens, Greece. FAU - Khanna, Sadhvi AU - Khanna S AD - Novartis Pharma S.A.S, Rueil-Malmaison, France. FAU - Bossen, Claudia AU - Bossen C AD - Novartis Pharma AG, Basel, Switzerland. FAU - Carbini, Mariana AU - Carbini M AD - Novartis Pharma AG, Basel, Switzerland. FAU - Turri, Sabine AU - Turri S AD - Novartis Pharma S.A.S, Rueil-Malmaison, France. FAU - Myers, Andrea AU - Myers A AD - Novartis Pharmaceuticals Corporation, East Hanover, NJ. FAU - Cho, Byoung Chul AU - Cho BC AUID- ORCID: 0000-0002-5562-270X AD - Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. LA - eng SI - ClinicalTrials.gov/NCT03447769 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20231003 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 37CQ2C7X93 (canakinumab) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adult MH - Humans MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/surgery MH - *Lung Neoplasms/drug therapy/surgery MH - Cisplatin MH - Neoplasm Recurrence, Local/drug therapy MH - Chemotherapy, Adjuvant MH - Double-Blind Method EDAT- 2023/10/03 18:43 MHDA- 2024/01/08 06:42 CRDT- 2023/10/03 16:03 PHST- 2024/01/08 06:42 [medline] PHST- 2023/10/03 18:43 [pubmed] PHST- 2023/10/03 16:03 [entrez] AID - 10.1200/JCO.23.00910 [doi] PST - ppublish SO - J Clin Oncol. 2024 Jan 10;42(2):180-191. doi: 10.1200/JCO.23.00910. Epub 2023 Oct 3.