111P - Ceritinib treatment of patients (Pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) and brain metastases: ASCEND-1 trial experience

Date 17 April 2015
Event ELCC 2015
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Dong-Wan Kim
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors D. Kim1, R. Mehra2, D. Tan3, E. Felip4, T. Szczudlo5, S. Sutradhar5, K. Rodriguez Lorenc5, A.T. Shaw6
  • 1Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 2Medical Oncology, Fox Chase Cancer Center, 19111 - Philadelphia/US
  • 3Medical Oncology, National Cancer Center Singapore, 169610 - Singapore/SG
  • 4Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 5Medical Oncology, Novartis Pharmaceuticals Corporation, NJ 07936 - East Hanover/US
  • 6Thoracic Oncology, Massachusetts General Hospital, 02125 - Boston/US

Abstract

Aim/Background

Brain metastases (BM) are a common, challenging cause of disease progression in ALK+ NSCLC pts including those receiving crizotinib (CRZ). Ceritinib, a novel oral ALK inhibitor (ALKi) with 20-fold greater potency than CRZ in enzymatic assays, has blood-brain barrier penetration in preclinical studies, and showed intracranial activity in the pivotal ASCEND-1 study. Here, further efficacy and safety were evaluated in pts with BM from ASCEND-1.

Methods

Pts with ALK+ NSCLC including those with clinically/neurologically stable BM received ceritinib 750 mg/day. Pts in the April 2014 data cut-off with baseline and post-baseline CT/MRI scans were retrospectively analyzed by 2 independent neuroradiologists blinded to systemic response and investigator assessment.

Results

Overall, 246 pts with ALK+ NSCLC were included in ASCEND-1; 83 were ALKi naïve and 163 were ALKi pretreated. Overall response rate for ALKi-naïve and ALKi-pretreated pts was 72.3% (95% Confidence Interval [CI]: 61.4, 81.6) and 56.4% (95% CI: 48.5, 64.2), respectively. Progression-free survival (PFS) was 18.4 (95% CI: 11.1, NE) mths in ALKi-naïve and 6.9 (95% CI: 5.6, 8.7) mths in ALKi-pretreated pts. Of the 94 pts with measurable or non-measurable BM and retrospectively analyzed MRI/CT scans, the median age was 52 years, with 86.2% having an ECOG PS ≤1. Intracranial disease control rate (complete and partial response + stable disease) was 78.9% (95% CI: 54.4, 93.9) in ALKi-naïve (n = 19) and 65.3% (95% CI: 53.5, 76.0) in ALKi-pretreated pts (n = 75). Six of 11 pts with measurable (RECIST 1.1) BM who had not received prior radiotherapy achieved a partial response. Median time to tumor response in all pts with measurable baseline BM (n = 22) was 6.1 weeks. Median ceritinib treatment exposure was 49.6 weeks (range: 7.9–83.0) in ALKi-naïve and 40.6 weeks (range: 0.4–95.1) in ALKi-pretreated pts with baseline BM evaluated by MRI/CT. The most common adverse events (all grades) in all pts and the BM subset were diarrhea (86.6% vs 81.9%), nausea (83.3% vs 86.2%), and vomiting (61.0% vs 66.0%).

Conclusions

Ceritinib has clinically significant, durable efficacy in pts with ALK+ NSCLC, including pts with BM.

Clinical trial identification NCT01283516 Released: 24 January 2011

Disclosure

D.-W. Kim: Consultation for Novartis, Pfizer.

R. Mehra: Consultant for Novartis, Genentech and Bayer/Onyx Spouse is an employee of Novartis.

E. Felip: Consultation: Lilly, Pfizer, Roche, Boehringer Ingelheim. Speaker's Bureau: BMS, Novartis, AstraZeneca.

T. Szczudlo: Novartis employee and stock owner.

K. Rodriguez Lorenc and S. Sutradhar: Employee of Novartis Pharmaceutical Corporation.

A.T. Shaw: Consulting: Pfizer, Novartis, Roche, Genentech, Anad, Chiangaii, Ignyta, Daiichi.

All other authors have declared no conflicts of interest.