1. A cura di Filippo de Marinis
OASI ALK ASCO 2017
A cura di Filippo de Marinis

2. 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

3. 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 (NCT ). 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: NCT

4. 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

5. Presented By Alice Shaw at 2017 ASCO Annual Meeting
Slide 2
Presented By Alice Shaw at 2017 ASCO Annual Meeting

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

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

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

9. Presented By Alice Shaw at 2017 ASCO Annual Meeting
Study design
Presented By Alice Shaw at 2017 ASCO Annual Meeting

10. Statistical considerations
Presented By Alice Shaw at 2017 ASCO Annual Meeting

11. Presented By Alice Shaw at 2017 ASCO Annual Meeting
Study conduct
Presented By Alice Shaw at 2017 ASCO Annual Meeting

12. Baseline characteristics
Presented By Alice Shaw at 2017 ASCO Annual Meeting

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

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

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

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

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

18. Secondary endpoint: <br />Time to CNS progression (by IRC, ITT)
Presented By Alice Shaw at 2017 ASCO Annual Meeting

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

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

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

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

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

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

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

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

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