Phase 2 study of ceritinib in ALKi-naïve patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC): Whole body responses in the overall pt group and in pts with baseline brain metastases (BM)
2016; Elsevier BV; Volume: 27; Linguagem: Inglês
10.1093/annonc/mdw383.03
ISSN1569-8041
AutoresEnriqueta Felip, Sergey Orlov, K. Park, Chong‐Jen Yu, Chun‐Ming Tsai, Makoto Nishio, Manuel Cobo, Mark J. McKeage, Wu‐Chou Su, Tony Mok, Giorgio V. Scagliotti, David R. Spigel, Vanessa Q. Passos, V. Chen, Florence Munarini, Alice T. Shaw,
Tópico(s)Cancer therapeutics and mechanisms
ResumoIn the pivotal ASCEND-1 study, ceritinib showed whole body efficacy in ALKi-naïve pts with ALK+ NSCLC (including those with baseline BM), most of whom had received multiple prior therapies; median progression-free survival (mPFS) was 18.4 mo. The ASCEND-3 single-arm, open-label multicentre study evaluated the efficacy and safety of ceritinib in previously treated ALKi-naïve pts with ALK+ NSCLC (NCT01685138). Pts enrolled worldwide received oral ceritinib 750 mg/d (fasted) from 21 Jan 2013. Whole body efficacy was assessed by investigator (inv) and by Blinded Independent Review Committee (BIRC). Prior chemotherapy (≤3 lines) was permitted. Data cutoff was 15 Nov 2015. Of 124 pts receiving ceritinib, 122 (98.4%) had received prior antineoplastic regimens (with 31 [25%] receiving ≥3). Of the 124 pts, 49 (39.5%) had baseline BM. Median time from diagnosis to initiation of ceritinib was 13.5 mo (range 1.0–283.1); median duration of exposure was 22.5 mo (range 0.1–32.8); median follow-up was 23.1 mo (range 0.6–32.8). mPFS was 16.6 mo (95% CI 11.0, 22.1) by inv, and 18.4 mo (95% CI 10.9, 26.3) by BIRC. The table shows efficacy in all pts, and in pts by baseline BM status. The most frequently reported AEs were gastrointestinal (GI): diarrhoea (85.5%), nausea (77.4%) and vomiting (71.8%). Most GI AEs were Grade 1/2. Grade 3/4 diarrhoea, nausea and vomiting occurred in 3.2%, 6.5% and 6.5% of pts, respectively. Overall, 11.3% of pts discontinued due to AEs, with no particular AE predominating. Consistent with ASCEND-1, ceritinib resulted in a durable mPFS of 16.6/18.4 mo by inv/BIRC in ALKi-naïve pts with ALK+ NSCLC, of whom 54.8% had received ≥2 prior antineoplastic regimens. Whole body response rates were robust, irrespective of the presence of baseline BM. No new safety signals were identified in this study.
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