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

Abstract

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.

Keywords:

• ALK + NSCLC
• Ceritinib
• Post-progression survival
• Time to progression

Notes

Transparency

Declaration of funding

This work was supported by Novartis Pharmaceuticals Corporation.

Declaration of financial/other relationships

J.Z. has disclosed that he is an employee of Novartis Pharmaceuticals Corporation and owns stock/stock options. J.S., Z.-Y.Z., J.L., and X.C. (prior employee) have disclosed that they are employees of Analysis Group Inc., which has received consultancy fees from Novartis Pharmaceuticals Corporation. G.L. has disclosed that he is a Clinician Scientist and Associate Professor of Medicine and Epidemiology at the University of Toronto, and Princess Margaret Cancer Centre. He holds the Alan B. Brown Chair on Molecular Genomics. He has received honoraria from Novartis, Pfizer, Roche, and Astra Zeneca.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors would like to thank all investigators and patients who participated in the ASCEND-1 and ASCEND-2 studies. Editorial assistance was provided by Shelley Batts PhD, an employee of Analysis Group Inc.

Previous presentation: A synopsis of the current research was accepted as oral presentation at the 16th World Congress of Lung Cancer, 6 − 9 September 2015, Denver, CO, USA.

Notes

1 Zykadia is a registered trade name of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

2 Xalkori is a registered trade name of Pfizer Labs Division of Pfizer Inc., New York, New York, USA