OASI ALK ASCO 2017 A cura di Filippo

OASI ALK ASCO 2017 A cura di Filippo de Marinis

Alectinib versus crizotinib in treatment-naive advanced ALK-positive non-small cell lung cancer (NSCLC): Primary results of the global phase III ALEX study Alice Tsang Shaw

Background: Alectinib, a TKI targeting ALK, has shown robust efficacy in crizotinib-naïve/resistant ALK+ NSCLC. J-ALEX showed superiority of alectinib 300 mg BID vs crizotinib in Japanese pts with crizotinib-naïve ALK+ NSCLC (progression-free survival [PFS] HR 0. 34, p<0. 0001). We report primary results from the ALEX study of first-line alectinib 600 mg BID vs crizotinib in advanced ALK+ NSCLC (NCT 02075840). Methods: This open-label randomized multicenter phase III study enrolled pts with stage IIIB/IV ALK+ NSCLC, determined by central IHC testing. Eligible pts had ECOG PS 0– 2 and no prior systemic therapy for advanced NSCLC. Pts with asymptomatic CNS metastases were allowed. Pts (n=303) were randomized 1: 1 to receive alectinib 600 mg or crizotinib 250 mg BID. Primary endpoint: Investigator (Inv)-assessed PFS (RECIST v 1. 1), with systematic CNS imaging in all pts. Secondary endpoints included independent review committee (IRC)-assessed PFS, IRC-assessed time to CNS progression (TTP), objective response rate (ORR), overall survival (OS) and safety. Results: At the primary data cut-off (9 Feb 2017), alectinib demonstrated statistically significant superiority vs crizotinib, reducing risk of progression/death by 53% (HR 0. 47, 95% CI 0. 34– 0. 65, p<0. 0001); alectinib median PFS was not reached (95% CI 17. 7–NE) vs crizotinib 11. 1 months (95% CI 9. 1– 13. 1). Key secondary endpoints showed superiority for alectinib vs crizotinib, respectively: IRC PFS, HR 0. 50 (95% CI 0. 36– 0. 70; p<0. 0001); median PFS 25. 7 months (95% CI 19. 9–NE) vs 10. 4 months (95% CI 7. 7– 14. 6); CNS TTP, causespecific HR of CNS progression 0. 16 (95% CI 0. 10– 0. 28; p<0. 0001); ORR (Inv) 83% (95% CI 76– 89) vs 76% (95% CI 68– 82), p=0. 09; OS, based on 25% events, HR 0. 76 (95% CI 0. 48– 1. 20; p=0. 24). Grade 3/4 AEs were less frequent with alectinib, 41%, vs 50% with crizotinib; fatal AEs occurred in 3% vs 5%, respectively. Rates of AEs leading to discontinuation, dose reduction and interruption were lower with alectinib. Conclusions: Alectinib showed superior efficacy and favorable tolerability compared with crizotinib. ALEX results support alectinib as a new standard of care for treatment-naïve ALK+ NSCLC. Funding: F. Hoffmann-La Roche Clinical trial information: NCT 02075840

Alectinib vs crizotinib in treatment-naïve advanced ALK+ NSCLC: primary results of the global phase III ALEX study (LBA 9008) Presented By Alice Shaw at 2017 ASCO Annual Meeting

Slide 2 Presented By Alice Shaw at 2017 ASCO Annual Meeting

ALK rearrangement in NSCLC Presented By Alice Shaw at 2017 ASCO Annual Meeting

Alectinib in ALK+ NSCLC Presented By Alice Shaw at 2017 ASCO Annual Meeting

Study rationale Presented By Alice Shaw at 2017 ASCO Annual Meeting

Study design Presented By Alice Shaw at 2017 ASCO Annual Meeting

Statistical considerations Presented By Alice Shaw at 2017 ASCO Annual Meeting

Study conduct Presented By Alice Shaw at 2017 ASCO Annual Meeting

Baseline characteristics Presented By Alice Shaw at 2017 ASCO Annual Meeting

Baseline CNS disease Presented By Alice Shaw at 2017 ASCO Annual Meeting

Primary endpoint: PFS, investigator-assessed Presented By Alice Shaw at 2017 ASCO Annual Meeting

Secondary endpoint: PFS, IRC-assessed Presented By Alice Shaw at 2017 ASCO Annual Meeting

PFS: analysis by subgroups* Presented By Alice Shaw at 2017 ASCO Annual Meeting

PFS by baseline CNS metastases status* Presented By Alice Shaw at 2017 ASCO Annual Meeting

Secondary endpoint: Time to CNS progression (by IRC, ITT) Presented By Alice Shaw at 2017 ASCO Annual Meeting

Objective response rate* Presented By Alice Shaw at 2017 ASCO Annual Meeting

CNS objective response rate* Presented By Alice Shaw at 2017 ASCO Annual Meeting

Secondary endpoint: OS Presented By Alice Shaw at 2017 ASCO Annual Meeting

Safety summary and exposure Presented By Alice Shaw at 2017 ASCO Annual Meeting

Adverse events, ≥ 10% between treatment arms Presented By Alice Shaw at 2017 ASCO Annual Meeting

Summary Presented By Alice Shaw at 2017 ASCO Annual Meeting

Conclusions Presented By Alice Shaw at 2017 ASCO Annual Meeting

Acknowledgments Presented By Alice Shaw at 2017 ASCO Annual Meeting

Slide 24 Presented By Alice Shaw at 2017 ASCO Annual Meeting