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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.
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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, hasshownrobustefficacy in crizotinib-naïve/resistantALK+ NSCLC. J-ALEX showedsuperiority of alectinib 300mg BID vs crizotinib in Japanesepts with crizotinib-naïve ALK+ NSCLC (progression-free survival [PFS] HR 0.34, p<0.0001). We report primaryresults from the ALEX study of first-line alectinib 600mg BID vs crizotinib in advancedALK+ NSCLC (NCT02075840). Methods: This open-labelrandomizedmulticenterphase III studyenrolledpts with stage IIIB/IV ALK+ NSCLC, determined by central IHC testing. Eligibleptshad ECOG PS 0–2 and no priorsystemic therapy for advanced NSCLC. Pts with asymptomatic CNS metastaseswereallowed. Pts (n=303) wererandomized 1:1 to receivealectinib 600mg or crizotinib 250mg BID. Primaryendpoint: Investigator (Inv)-assessed PFS (RECIST v1.1), with systematic CNS imaging in allpts. Secondaryendpointsincludedindependentreviewcommittee (IRC)-assessed PFS, IRC-assessed time to CNS progression (TTP), objectiveresponse rate (ORR), overallsurvival (OS) and safety. Results: At the primary data cut-off (9 Feb 2017), alectinibdemonstratedstatisticallysignificantsuperiority vs crizotinib, reducing risk of progression/death by 53% (HR 0.47, 95% CI 0.34–0.65, p<0.0001); alectinibmedian PFS wasnotreached (95% CI 17.7–NE) vs crizotinib 11.1 months (95% CI 9.1–13.1). Keysecondaryendpointsshowedsuperiority 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 AEswerelessfrequent with alectinib, 41%, vs 50% with crizotinib; fatalAEsoccurred in 3% vs 5%, respectively. Rates of AEsleading to discontinuation, dose reduction and interruptionwerelower with alectinib. Conclusions: Alectinibshowedsuperiorefficacy and favorabletolerabilitycompared with crizotinib. ALEX results support alectinibas a new standard of care for treatment-naïve ALK+ NSCLC. Funding: F. Hoffmann-La Roche Clinical trial information: NCT02075840
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
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: <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
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