Impact of the EML4-ALK variant on the efficacy of alectinib (ALC) in untreated ALK+ advanced NSCLC (aNSCLC) in the global phase III ALEX study
Invited conference paper presented and published in conference proceedings

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AbstractBackground: The ALEX study (NCT02075840) showed superior investigator (INV)-assessed PFS with ALC vs crizotinib (CZ) (stratified HR 0.47, 95% CI 0.34–0.65, p < 0.001): median PFS not estimable ALC vs 11.1 months [m] CZ. Follow-up analysis (cut-off Dec 1 2017) indicated a median PFS of 34.8m ALC vs 10.9m CZ (stratified HR 0.43, 95% CI 0.32–0.58) [Camidge et al. ASCO 2018]. We report efficacy data from ALEX by EML4-ALK variant group.

Methods: Patients (pts) with stage IIIB/IV ALK+ NSCLC (by central IHC) and no prior systemic therapy for aNSCLC were enrolled (asymptomatic CNS metastases allowed) and randomized 1:1 to receive ALC 600mg BID (n = 152) or CZ 250mg BID (n = 151). ALK rearrangement was assessed in baseline samples by next generation sequencing (NGS; FoundationOne® [tissue] and Foundation ACT [plasma]) using the primary data cut-off (Feb 9 2017). PFS (INV-assessed, RECIST v1.1), objective response rate (ORR) and duration of response (DoR) were assessed by EML4-ALK variant.

Results: Baseline demographics/PFS were comparable between the biomarker evaluable populations (BEP; n = 203 tissue, n = 222 plasma) and the ITT population (n = 303). ALK rearrangement was detected by NGS in 136/203 (67%; tissue) and 145/222 (65%; plasma) pts. EML4-ALK variants 1, 2 and 3a/b accounted for ∼90% of variants (variant 2 was least prevalent). In the primary data set analysis, no significant difference was observed in INV-assessed PFS or ORR between the EML4-ALK variant groups in both tissue and plasma BEPs for ALC- and CZ-treated pts (Table). Median DoR was similar for EML4-ALK variants 1, 2 and 3 in the ALC arm but not in the CZ arm. Efficacy data by independent review were comparable.

Conclusions: These exploratory post-hoc analyses from the ALEX study show that the greater efficacy benefit of ALC vs CZ in ALK+ aNSCLC appeared independent of the EML4-ALK variant.

Clinical trial identification: NCT02075840.

Legal entity responsible for the study: F. Hoffmann-La Roche.

Funding: F. Hoffmann-La Roche.
All Author(s) ListR Dziadziuszko, T S Mok, D R Camidge, A T Shaw, J Noe, M Nowicka, T Liu, E Mitry, S Peters
Name of ConferenceESMO 2018 Congress
Start Date of Conference19/10/2018
End Date of Conference23/10/2018
Place of ConferenceMunich
Country/Region of ConferenceGermany
Proceedings TitleAnnals of Oncology
Series TitlePoster Discussion
Number in SeriesAbst: 1379PD
Volume Number29
Issue NumberSuppl 8
LanguagesEnglish-United Kingdom
KeywordsALK, NSCLC

Last updated on 2020-04-07 at 00:41