Crizotinib is an oral tyrosine kinase inhibitor (TKI) approved for treatment of ALK+ advanced NSCLC. We report efficacy and safety from subgroups of pts aged ≥65 y included in PROFILE 1005, the largest clinical trial to date of an ALK TKI in ALK+ NSCLC.
PROFILE 1005 (NCT00932451) was a multicenter, single-arm phase 2 trial of crizotinib (250 mg twice daily; continuously) in pts with ALK+ NSCLC who had failed ≥1 line of systemic treatment for advanced/metastatic disease. Co-primary endpoints were objective response rate (ORR) per RECIST v1.1 and adverse events (AEs). Other efficacy endpoints included duration of response (DOR), progression-free survival (PFS) and overall survival (OS).
Of 1066 treated pts, 93 (54 female/39 male) and 79 pts (49 female/30 male) were aged 65–70 y and >70 y, respectively, at baseline (overall safety population). 908 out of 1066 pts, including 74 pts in the 65–70 y subgroup and 57 in the >70 y subgroup, were ALK+ by central FISH testing; all were evaluable for response. The table shows investigator-assessed efficacy endpoints for these pts. Most common TRAEs in the 65–70 (n = 93) and >70 y (n = 79) subgroups, respectively, were vision disorder (54.8% & 45.6%), nausea (50.5% & 57.0%), edema (43.0% & 57.0%), vomiting (41.9% & 51.9%) and diarrhea (39.8 % & 48.1%), mostly Grade 1/2, comparable to the safety profile of the overall safety population (n = 1066), but with some higher frequencies seen in the >70 y subgroup. In the 65–70 y and >70 y subgroups, respectively, 24.7% and 27.8% of pts had TRAEs leading to dose reductions (overall safety population, 18.3%), and 9.7% and 13.9% had TRAEs requiring permanent treatment discontinuation (overall safety population, 5.6%).
Efficacy and safety profiles in ALK+ NSCLC pts aged 65–70 or > 70 y were comparable to those previously reported for PROFILE 1005, with some TRAEs occurring at higher frequencies in pts >70 y.
Clinical trial identification
Legal entity responsible for the study
Medical writing support was provided by Jade Drummond and Brian Szente of inScience Communications, Springer Healthcare (Chester, UK and Philadelphia, PA, US), and was funded by Pfizer.
D. Moro-Sibilot: Membership of an advisory board or board of directors: MSD, BMS, Takeda, Roche, AstraZeneca, Ariad, Abbvie, Novartis, Pfizer, Lilly, Boehringer Ingelheim; Corporate sponsored research: Pfizer, Boehringer Ingelheim. M-J. Ahn: Membership of an advisory board or board of directors: AstraZeneca, Lilly, Lyzz. B. Halmos: Membership of an advisory board or board of directors: Pfizer, Novartis, Takeda, AstraZeneca, Boehringer Ingelheim, Genentech, Ignyta; Corporate sponsored research: Merck, Pfizer, Mirati, Boehringer Ingelheim, AstraZeneca, Takeda, Novartis, Eli Lilly; Other: Foundation Medicine, Guardant Health 360, Eli Lilly, Merck. G.J. Riely: Speakers or advisory board: Genetech; Grant/research support: Novartis, Roche/Genetech, Millenium, GlaxoSmithKline, Pfizer, Infinity Pharmaceuticals, Ariad. A.T. Shaw: Membership of an advisory board or board of directors: Blueprint Medicines, KSQ Therapeutics; Consulting or honoraria: Pfizer, Novartis, Genentech, Roche, Takeda, Ariad, Ignyta, Loxo, Blueprint, Natera, Foundation Medicine, EMD Serono. S. Lanzalone, A. Polli, K.D. Wilner: Stock ownership and employment: Pfizer. J. De Castro Carpeño: Advisory board: Roche, Takeda, Pfizer. All other authors have declared no conflicts of interest.Table: 1396P
|Patients With ALK+ NSCLC by Central FISH Testing|
|65–70 y (n = 74)||>70 y (n = 57)||PROFILE 1005 Total (n = 908)|
|Mean age, years (range)||67 (65–70)||76 (71–84)||52 (19–84)|
|ORR, % (95% CI)a||54.1 (42.1, 65.7)||47.4 (34.0, 61.0)||54.1 (50.8, 57.4)|
|Median DOR (Kaplan–Meier), months (95% CI)a||11.4 (8.3, 16.6)||12.4 (9.6, 14.1)||11.8 (10.4, 12.8)|
|Median PFS (Kaplan–Meier), months (95% CI)b||9.6 (5.5, 16.8)||11.6 (6.9, 15.1)||8.4 (7.1, 9.7)|
|Median PFS (Kaplan–Meier), months (95% CI)b||23.2 (17.6, 31.2)||17.0 (12.2, 22.4)||21.8 (19.4, 24.0)|
Calculated using the exact method based on the F distributionb
Based on Brookmeyer and Crowley method