Updated efficacy and safety from the global phase II NP28673 study of alectinib in patients (pts) with previously treated ALK+ non-small-cell lung cancer (NSCLC)

Background

Alectinib is an FDA-approved ALK inhibitor for pts with ALK+ NSCLC, who have progressed on, or are intolerant to, crizotinib. Alectinib has shown systemic and CNS activity in previously treated pts in two pivotal phase II trials (NCT01801111 [NP28673] and NCT01871805 [NP28761]). We report updated safety and efficacy (data cut-off 01 Feb 2016) from the global NP28673 study (previously at ECC 2015 [Barlesi et al]).

Methods

Pts ≥18 yrs, ECOG PS 0–2 with confirmed ALK+ NSCLC (by FDA-approved FISH) previously treated with crizotinib received alectinib 600mg BID until progression, death or withdrawal. Co-primary endpoints were objective response rate (ORR) by Independent Review Committee (IRC) in the response evaluable (RE) population using RECIST v1.1 and in pts who had prior chemo. Secondary endpoints included duration of response (DOR); CNS ORR and DOR; disease control rate (DCR); PFS; OS; and safety (CTC v4.0).

Results

138 pts were enrolled (ITT), median age 52 yrs; 110 had received prior chemo, 84 had baseline (BL) CNS mets. At this data cut-off, median follow-up was 21 months. The co-primary endpoint IRC ORR (n = 122) was 50.8% (95% CI 41.6–60.0); DCR: 78.7% (95% CI 70.4–85.6); median DOR: 15.2 months (95% CI 11.2–24.9); and median PFS: 8.9 months (95% CI 5.6–12.8). In pts with prior chemo (n = 96), IRC ORR was 44.8% (95% CI 34.6–55.3); DCR: 77.1% (95% CI 67.4–85.1) and median DOR: 14.7 months (95% CI 10.2–21.9). See table for data in pts with CNS mets at BL. Median OS in ITT pts was 26.0 months (95% CI 21.5–NE) after 44% events. Most common AEs (any grade): constipation (38%); fatigue (31%); peripheral oedema (30%). Rates of AEs leading to dose modification/interruption (28%) or withdrawal (9%) show good tolerability.

Conclusions

The updated NP28673 data show that alectinib is well tolerated and efficacy is robust, both systemically and in the CNS. The ongoing phase III ALEX trial is evaluating alectinib vs crizotinib in a first-line setting.

Clinical trial identification

NCT01801111 [NP28673] and NCT01871805 [NP28761].

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd

Funding

F. Hoffmann-La Roche Ltd

Disclosure

F. Barlesi: Advisory board and Corporate-sponsored research for F. Hoffman-La Roche. A-M.C. Dingemans: Roche Advisory board or board of directors. J.C-H. Yang: Membership on an Advisory Board for BI, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astrazeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, innopharma, Merrimack. S-H.I. Ou: Roche Advisory Board, Corporate Sponsored Research and Speakers Bureau. B. Hughes: Roche Advisory Board. H. Lena: Roche Corporate-sponsored research. W. Bordogna: Employment with Hoffmann-La Roche. S. Golding, B. Balas: Employee and Stock ownership for F. Hoffmann-La Roche. A. Zeaiter: Employee, Leadership and Stock Ownership for F. Hoffmann-La Roche. All other authors have declared no conflicts of interest.