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

<b>Objective</b>: 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 (Zykadia*) for the treatment of advanced anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). <b>Research design and methods</b>: 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. <b>Main outcome measures:</b> Main outcomes measured include TTP, PPS, and OS. <b>Results</b>: Patients with TTP ≥ 6 months experienced significantly longer PPS compared to those with TTP &lt; 6 months (median: 9.8 vs. 6.5 months, log-rank p-value &lt; 0.01). 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 &lt; 6 months. <b>Conclusions</b>: A longer duration of TTP after treatment with ceritinib was significantly associated with a longer duration of both PPS and OS.