Purpose: Effective treatments for resectable non-small-cell lung cancer (NSCLC) are limited and relapse rates are high. The interleukin (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. 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-1β 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.

Canakinumab as Adjuvant Therapy in Patients With Completely Resected Non–Small-Cell Lung Cancer: Results From the CANOPY-A Double-Blind, Randomized Clinical Trial / Garon, Edward B.; Lu, Shun; Goto, Yasushi; De Marchi, Pedro; Paz-Ares, Luis; Spigel, David R.; Thomas, Michael; Yang, James Chih-Hsin; Ardizzoni, Andrea; Barlesi, Fabrice; Orlov, Sergey; Yoshioka, Hiroshige; Mountzios, Giannis; Khanna, Sadhvi; Bossen, Claudia; Carbini, Mariana; Turri, Sabine; Myers, Andrea; Cho, Byoung Chul. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - STAMPA. - 42:2(2024), pp. 180-191. [10.1200/jco.23.00910]

Canakinumab as Adjuvant Therapy in Patients With Completely Resected Non–Small-Cell Lung Cancer: Results From the CANOPY-A Double-Blind, Randomized Clinical Trial

Thomas, Michael;Ardizzoni, Andrea;
2024

Abstract

Purpose: Effective treatments for resectable non-small-cell lung cancer (NSCLC) are limited and relapse rates are high. The interleukin (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. 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-1β 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.
2024
Canakinumab as Adjuvant Therapy in Patients With Completely Resected Non–Small-Cell Lung Cancer: Results From the CANOPY-A Double-Blind, Randomized Clinical Trial / Garon, Edward B.; Lu, Shun; Goto, Yasushi; De Marchi, Pedro; Paz-Ares, Luis; Spigel, David R.; Thomas, Michael; Yang, James Chih-Hsin; Ardizzoni, Andrea; Barlesi, Fabrice; Orlov, Sergey; Yoshioka, Hiroshige; Mountzios, Giannis; Khanna, Sadhvi; Bossen, Claudia; Carbini, Mariana; Turri, Sabine; Myers, Andrea; Cho, Byoung Chul. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - STAMPA. - 42:2(2024), pp. 180-191. [10.1200/jco.23.00910]
Garon, Edward B.; Lu, Shun; Goto, Yasushi; De Marchi, Pedro; Paz-Ares, Luis; Spigel, David R.; Thomas, Michael; Yang, James Chih-Hsin; Ardizzoni, Andrea; Barlesi, Fabrice; Orlov, Sergey; Yoshioka, Hiroshige; Mountzios, Giannis; Khanna, Sadhvi; Bossen, Claudia; Carbini, Mariana; Turri, Sabine; Myers, Andrea; Cho, Byoung Chul
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/963291
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 5
  • ???jsp.display-item.citation.isi??? ND
social impact