TY - JOUR
T1 - Short progression-free survival of ALK inhibitors sensitive to secondary mutations in ALK-positive NSCLC patients
AU - Haratake, Naoki
AU - Seto, Takashi
AU - Takamori, Shinkichi
AU - Toyozawa, Ryo
AU - Nosaki, Kaname
AU - Miura, Naoko
AU - Ohba, Taro
AU - Toyokawa, Gouji
AU - Taguchi, Kenichi
AU - Yamaguchi, Masafumi
AU - Shimokawa, Mototsugu
AU - Takenoyama, Mitsuhiro
N1 - Funding Information:
Dr Seto reports grants from Bayer Yakuhin, grants from Eisai, grants from Merck Serono, grants from Novartis Pharma, personal fees from Bristol-Myers Squibb, personal fees from Kyowa Hakko Kirin, personal fees from Mochida Pharmaceutical, personal fees from Ono Pharmaceutical, personal fees from Roche Singapore, personal fees from Showa Yakuhin, personal fees from Taiho Pharmaceutical, personal fees from Takeda Pharmaceutical, grants and personal fees from Astellas Pharma, grants and personal fees from AstraZeneca, grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Daiichi Sankyo, grants and personal fees from Eli Lilly Japan, grants and personal fees from Kissei Pharmaceutical, grants and personal fees from MSD, grants and personal fees from Nippon Boehringer Ingelheim, grants and personal fees from Pfizer Japan, grants and personal fees from Yakult Honsha, outside the submitted work. D. Nosaki reports grants from Novartis Pharma, personal fees from AstraZeneca, personal fees from Chugai Pharmaceutical, personal fees from Eli Lilly Japan, personal fees from Kyowa Hakko Kirin, personal fees from Nippon Boehringer Ingelheim, personal fees from Nippon Kayaku, personal fees from Ono Pharmaceutical, personal fees from Pfizer Japan, personal fees from Taiho Pharmaceutical, grants and personal fees from MSD, outside the submitted work. Dr. Takenoyama reports grants and personal fees from AstraZeneca, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Eli Lilly Japan, grants and personal fees from Nippon Boehringer Ingelheim, grants and personal fees from Ono Pharmaceutical, grants and personal fees from Taiho Pharmaceutical, personal fees from MSD, grants from Johnson & Johnson, grants from Kaketsuken, grants from Novartis Pharma, grants from Yakult Honsha, outside the submitted work. All other authors declare no competing interests.
Publisher Copyright:
© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Background: Most non-small cell lung cancer (NSCLC) patients relapse on anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) therapy because of acquired resistance. Rebiopsy is recommended to provide optimal therapy after relapse for some ALK-TKI therapies; however, little clinical data exists on the clinical efficacy of ALK-TKI tailored to secondary mutation. Methods: A retrospective study was conducted to analyze the patterns of ALK-TKI treatment and clinical outcomes, including progression free survival (PFS), of ALK-positive NSCLC patients who received rebiopsy. Based on the rebiopsy results, secondary mutations in the ALK gene that were shown to be associated with the efficacy of ALK-TKI therapy in the preclinical or clinical setting were defined as “sensitive mutations (SM)”. Results: Among 71 patients who received ALK-TKI for NSCLC at our institution, 20 patients received rebiopsy, and secondary SM were found in eight patients. The objective response rate (ORR) of the cases with SM who received ALK-TKI therapy was 88.9%, while the ORR of the patients without SM who received ALK TKI or chemotherapy was 20.0%; however, the PFS of the patients with SM was relatively short (with SM vs. without SM: 5.6 months vs. 5.1 months). Conclusions: The selection of ALK-TKI based on the rebiopsy result was associated with a high ORR and relatively short PFS. The mechanism responsible for the short PFS of sensitive ALK-TKI to secondary mutation should be clarified.
AB - Background: Most non-small cell lung cancer (NSCLC) patients relapse on anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) therapy because of acquired resistance. Rebiopsy is recommended to provide optimal therapy after relapse for some ALK-TKI therapies; however, little clinical data exists on the clinical efficacy of ALK-TKI tailored to secondary mutation. Methods: A retrospective study was conducted to analyze the patterns of ALK-TKI treatment and clinical outcomes, including progression free survival (PFS), of ALK-positive NSCLC patients who received rebiopsy. Based on the rebiopsy results, secondary mutations in the ALK gene that were shown to be associated with the efficacy of ALK-TKI therapy in the preclinical or clinical setting were defined as “sensitive mutations (SM)”. Results: Among 71 patients who received ALK-TKI for NSCLC at our institution, 20 patients received rebiopsy, and secondary SM were found in eight patients. The objective response rate (ORR) of the cases with SM who received ALK-TKI therapy was 88.9%, while the ORR of the patients without SM who received ALK TKI or chemotherapy was 20.0%; however, the PFS of the patients with SM was relatively short (with SM vs. without SM: 5.6 months vs. 5.1 months). Conclusions: The selection of ALK-TKI based on the rebiopsy result was associated with a high ORR and relatively short PFS. The mechanism responsible for the short PFS of sensitive ALK-TKI to secondary mutation should be clarified.
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U2 - 10.1111/1759-7714.13143
DO - 10.1111/1759-7714.13143
M3 - Article
C2 - 31338990
AN - SCOPUS:85069926622
SN - 1759-7706
VL - 10
SP - 1779
EP - 1787
JO - Thoracic Cancer
JF - Thoracic Cancer
IS - 9
ER -
