178P - Continuation of ceritinib beyond disease progression is associated with prolonged post-progression survival (PPS) in ALK+ NSCLC

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Cytotoxic agents
Non-small-cell lung cancer
Therapy
Biological therapy
Presenter Daniel Tan
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors D. Tan1, G. Liu2, D. Kim3, M. Thomas4, E. Felip5, J. Signorovitch6, J. Zhang7, T. Szczudlo8, A.T. Shaw9
  • 1Medical Oncology, National Cancer Center, 169610 - Singapore/SG
  • 2Medical Oncology, Princess Margaret Hospital, M5P 2H7 - Toronto/CA
  • 3Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 4Thoracic Oncology/internal Medicine, Thoraxklinik/University of Heidelberg, D-69126 - Heidelberg/DE
  • 5Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 6Health Economics And Outcomes Research, Analysis Group, Inc., 02199 - Boston/US
  • 7Global Oncology, Novartis Pharmaceuticals Corporation, 07936 - East Hanover/US
  • 8Global Medical Affairs, Novartis Pharmaceuticals Corporation, 07936 - East Hanover/US
  • 9Cancer Center, Massachusetts General Hospital, 02114 - Boston/US

Abstract

Background

Ceritinib has been shown to be efficacious with an acceptable tolerability profile for crizotinib (CRZ) pretreated advanced ALK+ NSCLC. However, patients (pts) who develop progressive disease (PD) after ceritinib treatment face limited treatment options. This study evaluated whether continuation of treatment with ceritinib beyond RECIST defined PD is associated with prolonged PPS.

Methods

CRZ pretreated pts who experienced RECIST defined progression in two single-arm clinical trials of ceritinib (ASCEND-1 [NCT01283516] and ASCEND-2 [NCT01685060]) were included in this retrospective analysis. Continuation of ceritinib was defined as >21 days of ceritinib use after PD. A Kaplan–Meier analysis for PPS was performed in pts stratified by continuation of ceritinib. Associations with PPS were studied using Cox proportional hazards models with adjustment for pt characteristics including age, sex, race, BMI, number of prior regimens, tumor histology, presence of brain metastases at screening, last known ECOG performance score prior to/at progression, whether progression was due to a new lesion, best response prior to progression, and time to progression. Additionally, landmark analyses to account for potential survivor bias were conducted among subgroups of pts with PPS >21 days or ≥6 months.

Results

Among 181 pts with progression, 99 (55%) continued ceritinib beyond PD. A higher proportion of pts continuing ceritinib had ECOG performance score 0/1 (97% vs 85%) and brain metastases (77% vs 63%) compared to those who discontinued. Pts continuing ceritinib experienced significantly longer PPS as compared to those who didn't (median: 12.0 vs 4.2 months, log-rank p-value 21 days (HR: 0.47) and ≥6 months (HR: 0.35).

Conclusions

Continuation of ceritinib beyond PD was associated with prolonged survival in this retrospective analysis of treatment for advanced ALK+ NSCLC.

Clinical trial identification

NCT01283516 (ASCEND-1); NCT01685060 (ASCEND-2)

Legal entity responsible for the study

Novartis Pharmaceuticals

Funding

Novartis Pharmaceuticals

Disclosure

D. Tan: Unrestricted education grant from Novartis; and consultancy fees from Novartis, Bayer and Boehringer Ingelheim. G. Liu: Honoraria from Astra Zaneca, Novartis, Pfizer and Roche. M. Thomas: Personal fees from Novartis, Roche, Pfizer, Lilly, BMS, MSD, Astrazeneca. E. Felip: Consultancies: Boehringer Ingelheim, Eli Lilly, Pfizer, Roche, BMS, MSD, Novartis. Committee member: MSD, Novartis, Roche. Fees paid by: Boehringer Ingelheim, Eli Lilly, Pfizer, Roche, BMS, MSD, Novartis. J. Signorovitch: Employee of Analysis Group Inc, which received funding for this research from Novartis. J. Zhang: Employee of Novartis Pharma and holds stock options with Novartis, BMS, Merk and AstraZeneca. T. Szczudlo: Employee and holds stock options with Novartis Pharma. A.T. Shaw: Grants and personal fees from Novartis; Personal fees from Ignyta, Blueprint, Pfizer, Ariad, Genentech, Roche, EMD Serono, Daiichi-sankyo and Taiho. All other authors have declared no conflicts of interest.