A cura di Filippo de Marinis 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 300mg 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 600mg BID vs crizotinib in advanced ALK+ NSCLC (NCT02075840). 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 600mg or crizotinib 250mg BID. Primary endpoint: Investigator (Inv)-assessed PFS (RECIST v1.1), 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, cause-specific 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: NCT02075840

Presented By Alice Shaw at 2017 ASCO Annual Meeting Alectinib vs crizotinib in treatment-naïve advanced ALK+ NSCLC: primary results of the global phase III ALEX study (LBA9008) Presented By Alice Shaw at 2017 ASCO Annual Meeting

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

Presented By Alice Shaw at 2017 ASCO Annual Meeting Study rationale Presented By Alice Shaw at 2017 ASCO Annual Meeting

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

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

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: <br />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

Presented By Alice Shaw at 2017 ASCO Annual Meeting Summary Presented By Alice Shaw at 2017 ASCO Annual Meeting

Presented By Alice Shaw at 2017 ASCO Annual Meeting Conclusions Presented By Alice Shaw at 2017 ASCO Annual Meeting

Presented By Alice Shaw at 2017 ASCO Annual Meeting Acknowledgments Presented By Alice Shaw at 2017 ASCO Annual Meeting

Presented By Alice Shaw at 2017 ASCO Annual Meeting Slide 24 Presented By Alice Shaw at 2017 ASCO Annual Meeting