Prognostic factors in crizotinib (CRZ)-resistant anaplastic lymphoma kinase (ALK+) non-small cell lung cancer (NSCLC) patients (Pts)

Abstract

Background: The aim of this analysis was to assess prognostic factors in patients with CRZ-resistant ALK+ NSCLC associated with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) based on the Phase 2 ALTA Trial (NCT02094573) of brigatinib. Methods: Analyses used data from ALTA Arm B (180 mg qd with a 7-day lead-in at 90 mg, N=110). Potential prognostic factors were evaluated using univariate and multivariate Cox proportional hazards models for PFS and OS, and logistic regression for ORR. Potential prognostic factors included age, sex, race, ECOG performance status prior radiotherapy (RT), prior RT to brain, prior chemotherapy, prior platinumbased chemotherapy, smoking status, number of prior regimens, best response to prior (Table presented) CRIZ, number of metastatic sites, and active brain lesions. ALTA trial was not powered to detect differences in outcomes by these factors, thus a threshold of p<0.5 was used to select variables into all models. Factors with hazard ratios >1.30 or<0.77 were also included in the final models for PFS and OS. Results: As of February 29, 2016, median follow-up was 8.3 months, and independent review committee (IRC) assessed median PFS was 15.6 months [95% CI: 11.0, NR] (31 events). Median OS was not reached (17 deaths). IRC-assessed ORR was 52.7% [95% CI: 43.0%, 62.3%]. Prognostic factors are shown in the table. Conclusions: In this analysis of CRZ-resistant ALK+ NSCLC patients, a history of prior chemotherapy was associated with longer PFS, while prior radiotherapy was associated with shorter PFS, both likely due to unmeasured patient characteristics. Never smokers had more than double the odds of response, versus current or former smokers. ECOG status 2 was nominally associated with shorter PFS and OS and lower ORR, and presence of active brain lesions was associated with longer OS.