Overall survival results of ceritinib in ALKi-naïve patients with ALK-rearranged NSCLC (ASCEND-3)

Date 19 October 2018
Event ESMO 2018 Congress
Session Poster Discussion session - NSCLC, metastatic 1
Topics Personalised/Precision Medicine
Presenter Enriqueta Felip
Authors E. Felip1, M. Nishio2, S. Orlov3, K. Park4, C. Yu5, C. Tsai6, M. Cobo7, M. McKeage8, W. Su9, T. Mok10, G.V. Scagliotti11, D. Spigel12, V.Q. Passos13, Z. Chen13, A.T. Shaw14
  • 1Oncology Service, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 2Department Of Thoracic Medical Oncology, Japanese Foundation for Cancer Research, Tokyo/JP
  • 3Oncology, Department of Thoracic Oncology, St. Petersburg State Medical University, St. Petersburg/RU
  • 4Department Of Medicine, Division of Hematology & Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/KR
  • 5Department Of Internal Medicine, National Taiwan University, Taipei/TW
  • 6Department Of Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei/TW
  • 7Medical Oncology, Medical Oncology Section, Hospital Regional Universitario Carlos Haya, IBIMA, Málaga/ES
  • 8School Of Medical Sciences, Auckland City Hospital and University of Auckland, Auckland/NZ
  • 9Department Of Internal Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan/TW
  • 10Clinical Oncology, Chinese University of Hong Kong, Shatin/CN
  • 11Department Of Oncology, University of Torino, Department of Oncology, Orbassano, Torino/IT
  • 12Department Of Oncology, Medical Oncology, Sarah Cannon Research Institute, Nashville, Tennessee/US
  • 13Oncology, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey/US
  • 14Mgh Cancer Center, Massachusetts General Hospital, Boston, Massachusetts/US

Abstract

Background

The previous analysis of phase 2, ASCEND-3 study (NCT01685138; data cutoff: November 15, 2015) demonstrated prolonged median progression-free survival (mPFS) with ceritinib 750 mg/d (fasted) in ALKi-naïve patients with ALK+ NSCLC, who had received ≤3 prior lines of chemotherapy. The current analysis (data cutoff: January 22, 2018) from ASCEND-3 study reports the final safety and efficacy results including overall survival (OS).

Methods

ASCEND-3 is a multicenter, single-arm, open-label, phase 2 study in ALKi-naïve patients (aged, ≥18 years) with locally advanced or metastatic ALK+ NSCLC, who had received ≤3 lines of chemotherapy. Patients received oral ceritinib 750 mg/d (fasted). Primary endpoint was overall response rate (ORR) per RECIST v1.1 (by investigator). Secondary endpoints were ORR (by blinded independent review committee [BIRC]); overall intracranial response rate (OIRR), duration of response (DOR), disease control rate (DCR), PFS (by investigator and BIRC); OS; and safety.

Results

Of 124 ceritinib-treated patients, 123 (99.2%) had received prior antineoplastic regimens (31 patients [25.0%], ≥3 regimens), and 49 (39.5%) had baseline brain metastases. Median follow-up time was 52.14 months (range, 48.4-60.1). Median duration of drug exposure was 23.2 months (range, 0.1-55.2). Median OS was 51.3 months (95% CI: 42.7, 55.3). Other efficacy results are shown in the table below. The most common adverse events (AEs [all grades], ≥60% of patients), suspected to be drug related, were diarrhea (83.1%), nausea (76.6%), and vomiting (69.4%). Grade 3/4 AEs suspected to be drug related were reported in 81 patients (65.3%). Overall, 18 patients (14.5%) had an AE leading to treatment discontinuation.

Investigator Assessment

(N* = 124)

BIRC Assessment

(N* = 124)
Overall response rate, n (%) (95% CI) 84 (67.7) (58.8, 75.9) 79 (63.7) (54.6, 72.2)
Disease control rate, n (%) (95% CI) 112 (90.3) (83.7, 94.9) 107 (86.3) (79.0, 91.8)

Median duration of response (in responders), months (95% CI)

M = 84

24.0 (14.8, 37.5)

M = 79

27.3 (16.6, 44.3)
Median progression-free survival, months (95% CI) 16.6 (11.0, 23.2) 19.4 (10.9, 29.3)

*Total number of patients included in the full analysis set.

Total number of patients with confirmed complete response or partial response.

Conclusions

Ceritinib demonstrated prolonged and clinically meaningful OS, PFS, and DOR in chemotherapy pretreated (≤3 lines), ALKi-naïve patients with ALK+ NSCLC. The safety profile is consistent with the previous studies.

Clinical trial identification

NCT01685138

Editorial Acknowledgement