Association between time to progression and subsequent survival inceritinib-treated patients with advanced ALK-positive non-small-cell lung cancer

Objective: Time to progression (TTP) is a surrogate marker of overall survival (OS). However, OS is also dependent on post-progression survival (PPS). This study evaluated the association between TTP and the duration of PPS among adult patients who received ceritinib (Zykadia1) for the treatment of advanced anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC).
Research design and methods: A pooled analysis was performed on 181 ASCEND-1 (phase I) and ASCEND-2 (phase II) patients who experienced disease progression while on ceritinib. TTP was assessed on its association with PPS in a Kaplan–Meier analysis and in Cox proportional hazard models, adjusted for clinical covariates.
Main outcome measures: Main outcomes measured include TTP, PPS, and OS.
Results: Patients with TTP ≥6 months experienced significantly longer PPS compared to those with TTP <6 months (median: 9.8 vs. 6.5 months, log-rank p-value < .01). When TTP was assessed as a continuous variable, every 3 months of longer TTP was associated with a 21% lower hazard of death following progression (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.63–1.00; adjusted HR: 0.79, 95% CI: 0.64–0.99). This positive association translated into an OS benefit: each 3 months of longer TTP was associated with a lower hazard of death (adjusted HR: 0.46, 95% CI: 0.37–0.58). Median OS was 20.0 months for patients with TTP ≥6 months and was 10.9 months for patients with TTP <6 months.
Conclusions: A longer duration of TTP after treatment with ceritinib was significantly associated with a longer duration of both PPS and OS.