436P - The efficacy of dose reduced crizotinib for advanced ALK-positive non-small cell lung cancer (436P)

Date 18 November 2017
Event ESMO Asia 2017 Congress
Session Poster lunch
Topics Cytotoxic agents
Thoracic malignancies
Personalised/Precision medicine
Non-small-cell lung cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological therapy
Presenter Maiko Naito
Citation Annals of Oncology (2017) 28 (suppl_10): x124-x143. 10.1093/annonc/mdx671
Authors M. Naito1, Y. Naoki1, S. Takata2, S. Ishii1, Y. Taniguchi1, N. Saijo1, A. Tamiya1, N. Omachi1, K. Okishio3, S. Morita2, A. Tanaka2, T. Shiroyama2, N. Morishita2, H. Suzuki2, N. Okamoto2, T. Hirashima2, S. Atagi3
  • 1Internal Medicine, Kinki-chuo Chest Medical Center, 591-8555 - Sakai/JP
  • 2Thoracic Oncology, Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, 583-8588 - Habikino/JP
  • 3Clinical Research Center, Kinki-chuo Chest Medical Center, Sakai/JP



Treatment of anaplastic lymphoma kinase tyrosine kinase inhibitor (ALK-TKI) is the standard treatment for advanced non-small-cell lung cancer (NSCLC) harboring ALK rearrangement. Numerous clinical trials show promising efficacy of crizotinib, the first generation ALK-TKI. However, crizotinib-associated adverse events requiring dose reduction are experienced in clinical settings, and the efficacy after dose reduction remains unclear.


We retrospectively assessed consecutive patients with ALK positive NSCLC, confirmed by IHC and/or FISH and/or RT-PCR, who were treated with crizotinib between October 2012 to June 2017 at Kinki-chuo Chest Medical Center and Osaka Habikino Medical Center. We divided the patients into two groups; standard dose group for crizotinib dose ≥400mg and low dose group for crizotinib dose


Twenty-four patients were enrolled in this study. Of these patients, 18 patients were analyzed, and 6 patients were excluded because RECIST-defined assessment was not evaluable in 3 patients and serious adverse events resulting in permanent discontinuation of crizotinib occurred in 3 patients. The median PFS was 6.6 months (range 1.0 to 65.2) in the analyzed 18 patients. Due to adverse events 14 patients required dose reduction, and by our definition, there were 13 patients in standard dose group and 5 patients in low dose group. The RR, DCR and PFS of standard dose group and low dose group were 52.6%, 52.6%, 6.1months and 80.0%, 100.0%, 13.7 months respectively.


Dose reduction of crizotinib due to its toxicity was frequently needed. However, we have experienced some cases which the efficacy of crizotinib was maintained after dose reduction of crizotinib.

Clinical trial identification

Legal entity responsible for the study

Shinji Atagi




Y. Taniguchi: Grant: Ono Pharmaceutical, Bristol-Myers Squibb Personal fee: Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Boehringer Ingelheim, A. Tamiya: Grant: Ono Pharmaceutical, Bristol-Myers Squibb Personal fee: Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Astra Zeneka, Eli Lilly, Boehringer Ingelheim, K. Okishio: Personal fee: Ono Pharmaceutical, S. Atagi: Honoraria: Chugai, Astra Zeneca, Taiho, Bristol-Myers Squibb, Eli Lilly, Ono, Boehringer Ingelheim Research funding: Pfizer, Merck Serono, Taiho, Yakult, Eli Lilly, Ono, Boehringer Ingelheim, Chugai, Astra Zeneca

All other authors have declared no conflicts of interest.