Abstract
Background: Mature progression-free survival (PFS) data from the phase III J-ALEX study showed superiority for alectinib versus crizotinib [hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.26-0.52; median PFS 34.1 versus 10.2 months, respectively] in advanced ALK (anaplastic lymphoma kinase)-positive non-small-cell lung cancer (NSCLC). Overall survival (OS) data were immature (HR 0.80, 99.8799% CI 0.35-1.82) at the time of data cut-off (30 June 2018). We report final OS data after ≥5 years of follow-up. Patients and methods: ALK inhibitor naive Japanese patients who were chemotherapy naive or had received one prior chemotherapy regimen were enrolled. Patients were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was independent review facility-assessed PFS, with OS (not fully powered) as a secondary endpoint. Results: Median duration of OS follow-up was 68.6 months with alectinib and 68.0 months with crizotinib. Treatment with alectinib did not prolong OS relative to crizotinib (HR 1.03, 95.0405% CI 0.67-1.58; P = 0.9105). Five-year OS rates were 60.9% (95% CI 51.4-70.3) with alectinib and 64.1% (95% CI 54.9-73.4) with crizotinib. In total, 91.3% (n = 95/104) of crizotinib-treated patients and 46.6% (n = 48/103) of alectinib-treated patients received at least one subsequent anticancer therapy. After study drug discontinuation, 78.8% of patients in the crizotinib arm switched to alectinib, while 10.7% of patients in the alectinib arm switched to crizotinib as a first subsequent anticancer therapy. Patients randomized to crizotinib tended to switch treatment earlier than those randomized to alectinib. Conclusion: Final OS analysis from J-ALEX did not show superiority of alectinib to crizotinib; this result was most likely confounded by treatment crossover. Alectinib remains a standard of care for the treatment of patients with advanced ALK-positive NSCLC.
| Original language | English |
|---|---|
| Article number | 100527 |
| Journal | ESMO Open |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Aug 2022 |
Keywords
- alectinib
- ALK-positive NSCLC
- crizotinib
- J-ALEX
- overall survival
ASJC Scopus subject areas
- Oncology
- Cancer Research
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In: ESMO Open, Vol. 7, No. 4, 100527, 08.2022.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Final overall survival analysis from the phase III J-ALEX study of alectinib versus crizotinib in ALK inhibitor-naïve Japanese patients with ALK-positive non-small-cell lung cancer
AU - Hotta, K.
AU - Hida, T.
AU - Nokihara, H.
AU - Morise, M.
AU - Kim, Y. H.
AU - Azuma, K.
AU - Seto, T.
AU - Takiguchi, Y.
AU - Nishio, M.
AU - Yoshioka, H.
AU - Kumagai, T.
AU - Watanabe, S.
AU - Goto, K.
AU - Satouchi, M.
AU - Kozuki, T.
AU - Shukuya, T.
AU - Nakagawa, K.
AU - Mitsudomi, T.
AU - Yamamoto, N.
AU - Asakawa, T.
AU - Yoshimoto, T.
AU - Takata, S.
AU - Tamura, T.
N1 - Funding Information: The authors gratefully acknowledge the investigators, staff, and patients involved in this study. Third-party medical writing assistance, under the direction of the authors, was provided by Joanne Bowes, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by Chugai Pharmaceutical Co. Ltd. T. Kumagai is deceased. This paper is dedicated to his memory. This work was supported by Chugai Pharmaceutical Co. Ltd (no grant number). KH declares personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb (BMS), Chugai, Lilly, MSD, Ono, Pfizer, Taiho, and Takeda; and grants from AstraZeneca, BMS, Chugai, Lilly, AbbVie, and MSD. TH declares grants and personal fees from AstraZeneca, BMS, Chugai, Kissei, MSD, Nippon Boehringer Ingelheim, Novartis, Ono, Pfizer, Taiho, and Takeda; and grants from AbbVie, Astellas, Daiichi-Sankyo, Eisai, Ignyta, Janssen, and Merck Serono. HN declares honoraria for lectures from AstraZeneca, Chugai, Nippon Boehringer Ingelheim, Pfizer, and Eli Lilly Japan; institutional grants from AstraZeneca, Chugai, and Pfizer. MM declares grants and personal fees from AstraZeneca, BMS, Chugai, Eli Lilly, Kissei, Merck Serono, Nippon Boehringer Ingelheim, Novartis, Ono, Pfizer, and Taiho. YHK declares lecture fees from Chugai, AstraZeneca, Eli Lilly, Boehringer Ingelheim, MSD, Taiho, and Nippon Kayaku. KA declares honoraria from AstraZeneca, BMS, Chugai, MSD, and Ono. TS declares grants from AbbVie, Chugai, Daiichi-Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, Merck Biopharma, MSD, Novartis, Pfizer, and Takeda; personal fees from AstraZeneca, BMS, Chugai, Covidien Japan, Daiichi-Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon, Novartis, Ono, Pfizer, Taiho, Takeda, and Thermo Fisher Scientific; and is an employee of Precision Medicine Asia. YT declares grants and lecture fees from Chugai, Pfizer, Boehringer Ingelheim, Takeda, Novartis, Ono, Eli Lilly, AstraZeneca, MSD, Taiho, and Towa; grants from Chugai, Boehringer Ingelheim, Takeda, Taiho, Daiichi-Sankyo, Nippon Kayaku, and MSD, Eli Lilly, and Kyowa Hakko Kirin; and study support from BMS, MSD, AstraZeneca, and AbbVie. MN declares grants and personal fees from Ono, BMS, Pfizer, Chugai, Eli Lilly, Taiho, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Merck Biopharma, Daiichi-Sankyo, and Takeda; and personal fees from Boehringer Ingelheim, Teijin, and AbbVie. HY declares honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Delta-Fly Pharma, Lilly, Kyowa Kirin Co. Ltd, MSD, Novartis, Nippon Kayaku, Ono, Pfizer, and Taiho. TK declares grants from AstraZeneca, Chugai, Eli Lilly, Merck Biopharma, MSD, Nippon Boehringer Ingelheim, Ono, Pfizer, Taiho, Takeda, and The Osaka Foundation for the Prevention of Cancer and Lifestyle related Diseases; personal fees from BMS, Nippon Boehringer Ingelheim, Ono, Pfizer, and Taiho; and consulting fees from Takeda. SW declares grants and personal fees from Boehringer Ingelheim and personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Lilly, Nippon Kayaku, Novartis, Ono, Pfizer, and Taiho. KG declares honoraria or personal fees from Amgen Astellas BioPharma, Amgen, Amoy Diagnostics, Boehringer Ingelheim Japan, BMS, Bayer Yakuhin, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan, Guardant Health, Janssen, Kyowa Kirin, Life Technologies Japan, MSD, Novartis, Ono, Otsuka, Pfizer Japan, Taiho, and Takeda; institutional funding from Amgen Astellas BioPharma, Amen, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Bayer Yakuhin, Daiichi-Sankyo, Eisai, Eli Lilly Japan, Ignyta, Janssen, Kissei Pharmaceutical, Kyowa Kirin, Loxo Oncology, Medical & Biological Laboratories, Merck Biopharma, Merus, MSD, NEC, Novartis, Ono, Sumitomo Dainippon Pharma, Spectrum Pharmaceuticals, Sysmex, Haihe Biopharma, Taiho, Takeda, and Turning Point Therapeutics. MS declares honoraria from Chugai, Pfizer, Takeda, AstraZeneca, MSD, Novartis, Eli Lilly, Bristol-Myers Squibb, Ono, Taiho, and Merck; grants from Chugai, MSD, IQVIA, EPS, Janssen, Amgen, Taiho, Ono, Pfizer, AbbVie, Daiichi-Sankyo, and Eisai. TK declares grants and personal fees from Chugai, AstraZeneca, Eli Lilly Japan, Taiho, BMS, MSD, Kyowa Hakko Kirin, Daiichi-Sankyo, and AbbVie; grants from Merck Biopharma, Amgen, and Sanofi; and personal fees from Ono, Pfizer Japan, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis, Takeda, and Bayer. TS declares honoraria or personal fees from AstraZeneca, Chugai, Boehringer Ingelheim, Novartis, MSD, Taiho, Daiichi-Sankyo, Ono, BMS, Nippon Kayaku, and Pfizer; and grants from AstraZeneca, Chugai, Boehringer Ingelheim, Novartis, and MSD. KN declares honoraria from Astellas, AstraZeneca, MSD, Ono, Daiichi-Sankyo, Taiho, BMS, Medical Review, Thermo Fisher Scientific, KYORIN, Nikkei Business Publications, Takeda, Chugai, Eli Lilly Japan, Merck Biopharma, Novartis, Pfizer Japan, CareNet, YODOSHA, Hisamitsu, MEDICUS SHUPPAN Publishers, Yomiuri Telecasting Corporation, Nanzando, Roche Diagnostics, Nippon Kayaku, Bayer Yakuhin, Kyowa Kirin, AbbVie, Amgen, 3H Clinical Trial, Nichi-Iko, Nippon Boehringer Ingelheim, and Medical Mobile Communications; research funding from MSD, ICON Japan, Takeda, Eli Lilly Japan, BMS, Taiho, PARAXEL International, Ono, Sysmex Corporation, A2 Healthcare, AbbVie, Chugai, Nippon Boehringer Ingelheim, SymBio Pharmaceuticals, AstraZeneca, Astellas, Novartis, EPS International, CMIC Shift Zero, Eisai, Mochida, GlaxoSmithKline, Kyowa Hakko Kirin, EPS Corporation, Daiichi-Sankyo, IQVIA Services Japan/Quintiles, Pfizer Japan, Bayer Yakuhin, Otsuka, PRA Health Sciences, Merck Biopharma, Covance Japan, Medical Research Support, Sanofi, Syneos Health, Pfizer R&D Japan, PPD-SNBL, and Japan Clinical Research Operations; consulting or advisor role for Astellas, Pfizer Japan, Takeda, KYORIN, Eli Lilly Japan, and Ono. TM declares honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai, MSD, Nippon Boehringer Ingelheim, Novartis, Ono, Pfizer, Taiho, Takeda, Amgen, Invitae, Merck Biopharma, Thermo Fisher Scientific, and Eli Lilly; research grants from Daiichi-Sankyo, MSD, Nippon Boehringer Ingelheim, Chugai, Ono, Taiho, Ethicon, and Bridge Biotherapeutics. NY declares consulting fees from Chugai, honoraria or personal fees from MSD, AstraZeneca, Ono, Thermo Fisher Scientific, Daiichi-Sankyo, Taiho, Takeda, Chugai, Eli Lilly Japan, Boehringer Ingelheim, Novartis, Pfizer, BMS, Nippon Kayaku, GlaxoSmithKline, Sanofi, Hisamitsu, and Merck Biopharma; data safety monitoring board or advisory board participation for MSD, AstraZeneca, Ono, Taiho, Takeda, Chugai, Eli Lilly Japan, Boehringer Ingelheim, Novartis, Pfizer, BMS, Life Technologies Japan, Nippon Kayaku, Amgen, Guardant Health Japan, and Janssen; leadership or fiduciary role in The Japan Lung Cancer Society, Japanese Association of Supportive Care in Cancer, and West Japan Oncology Group. TA, TY, and ST are employees of Chugai. TT declares honoraria, personal fees, and grants from Chugai, Taiho, Eli Lilly, Ono, Nippon Boehringer Ingelheim, BMS, Daiichi-Sankyo, Eisai, Yakult Honsha, Novartis, Astellas, MSD, Nippon Kayaku, Kyowa Kirin, and CMIC ShiftZero. Qualified researchers may request access to individual patient-level data through the clinical study data request platform (www.clinicalstudydatarequest.com). For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html). Funding Information: The authors gratefully acknowledge the investigators, staff, and patients involved in this study. Third-party medical writing assistance, under the direction of the authors, was provided by Joanne Bowes, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by Chugai Pharmaceutical Co. Ltd. T. Kumagai is deceased. This paper is dedicated to his memory. Funding Information: KH declares personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb (BMS), Chugai, Lilly, MSD, Ono, Pfizer, Taiho, and Takeda; and grants from AstraZeneca, BMS, Chugai, Lilly, AbbVie, and MSD. TH declares grants and personal fees from AstraZeneca, BMS, Chugai, Kissei, MSD, Nippon Boehringer Ingelheim, Novartis, Ono, Pfizer, Taiho, and Takeda; and grants from AbbVie, Astellas, Daiichi-Sankyo, Eisai, Ignyta, Janssen, and Merck Serono. HN declares honoraria for lectures from AstraZeneca, Chugai, Nippon Boehringer Ingelheim, Pfizer, and Eli Lilly Japan; institutional grants from AstraZeneca, Chugai, and Pfizer. MM declares grants and personal fees from AstraZeneca, BMS, Chugai, Eli Lilly, Kissei, Merck Serono, Nippon Boehringer Ingelheim, Novartis, Ono, Pfizer, and Taiho. YHK declares lecture fees from Chugai, AstraZeneca, Eli Lilly, Boehringer Ingelheim, MSD, Taiho, and Nippon Kayaku. KA declares honoraria from AstraZeneca, BMS, Chugai, MSD, and Ono. TS declares grants from AbbVie, Chugai, Daiichi-Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, Merck Biopharma, MSD, Novartis, Pfizer, and Takeda; personal fees from AstraZeneca, BMS, Chugai, Covidien Japan, Daiichi-Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon, Novartis, Ono, Pfizer, Taiho, Takeda, and Thermo Fisher Scientific; and is an employee of Precision Medicine Asia. YT declares grants and lecture fees from Chugai, Pfizer, Boehringer Ingelheim, Takeda, Novartis, Ono, Eli Lilly, AstraZeneca, MSD, Taiho, and Towa; grants from Chugai, Boehringer Ingelheim, Takeda, Taiho, Daiichi-Sankyo, Nippon Kayaku, and MSD, Eli Lilly, and Kyowa Hakko Kirin; and study support from BMS, MSD, AstraZeneca, and AbbVie. MN declares grants and personal fees from Ono, BMS, Pfizer, Chugai, Eli Lilly, Taiho, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Merck Biopharma, Daiichi-Sankyo, and Takeda; and personal fees from Boehringer Ingelheim, Teijin, and AbbVie. HY declares honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Delta-Fly Pharma, Lilly, Kyowa Kirin Co. Ltd, MSD, Novartis, Nippon Kayaku, Ono, Pfizer, and Taiho. TK declares grants from AstraZeneca, Chugai, Eli Lilly, Merck Biopharma, MSD, Nippon Boehringer Ingelheim, Ono, Pfizer, Taiho, Takeda, and The Osaka Foundation for the Prevention of Cancer and Lifestyle related Diseases; personal fees from BMS, Nippon Boehringer Ingelheim, Ono, Pfizer, and Taiho; and consulting fees from Takeda. SW declares grants and personal fees from Boehringer Ingelheim and personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Lilly, Nippon Kayaku, Novartis, Ono, Pfizer, and Taiho. KG declares honoraria or personal fees from Amgen Astellas BioPharma, Amgen, Amoy Diagnostics, Boehringer Ingelheim Japan, BMS, Bayer Yakuhin, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan, Guardant Health, Janssen, Kyowa Kirin, Life Technologies Japan, MSD, Novartis, Ono, Otsuka, Pfizer Japan, Taiho, and Takeda; institutional funding from Amgen Astellas BioPharma, Amen, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Bayer Yakuhin, Daiichi-Sankyo, Eisai, Eli Lilly Japan, Ignyta, Janssen, Kissei Pharmaceutical, Kyowa Kirin, Loxo Oncology, Medical & Biological Laboratories, Merck Biopharma, Merus, MSD, NEC, Novartis, Ono, Sumitomo Dainippon Pharma, Spectrum Pharmaceuticals, Sysmex, Haihe Biopharma, Taiho, Takeda, and Turning Point Therapeutics. MS declares honoraria from Chugai, Pfizer, Takeda, AstraZeneca, MSD, Novartis, Eli Lilly, Bristol-Myers Squibb, Ono, Taiho, and Merck; grants from Chugai, MSD, IQVIA, EPS, Janssen, Amgen, Taiho, Ono, Pfizer, AbbVie, Daiichi-Sankyo, and Eisai. TK declares grants and personal fees from Chugai, AstraZeneca, Eli Lilly Japan, Taiho, BMS, MSD, Kyowa Hakko Kirin, Daiichi-Sankyo, and AbbVie; grants from Merck Biopharma, Amgen, and Sanofi; and personal fees from Ono, Pfizer Japan, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis, Takeda, and Bayer. TS declares honoraria or personal fees from AstraZeneca, Chugai, Boehringer Ingelheim, Novartis, MSD, Taiho, Daiichi-Sankyo, Ono, BMS, Nippon Kayaku, and Pfizer; and grants from AstraZeneca, Chugai, Boehringer Ingelheim, Novartis, and MSD. KN declares honoraria from Astellas, AstraZeneca, MSD, Ono, Daiichi-Sankyo, Taiho, BMS, Medical Review, Thermo Fisher Scientific, KYORIN, Nikkei Business Publications, Takeda, Chugai, Eli Lilly Japan, Merck Biopharma, Novartis, Pfizer Japan, CareNet, YODOSHA, Hisamitsu, MEDICUS SHUPPAN Publishers, Yomiuri Telecasting Corporation, Nanzando, Roche Diagnostics, Nippon Kayaku, Bayer Yakuhin, Kyowa Kirin, AbbVie, Amgen, 3H Clinical Trial, Nichi-Iko, Nippon Boehringer Ingelheim, and Medical Mobile Communications; research funding from MSD, ICON Japan, Takeda, Eli Lilly Japan, BMS, Taiho, PARAXEL International, Ono, Sysmex Corporation, A2 Healthcare, AbbVie, Chugai, Nippon Boehringer Ingelheim, SymBio Pharmaceuticals, AstraZeneca, Astellas, Novartis, EPS International, CMIC Shift Zero, Eisai, Mochida, GlaxoSmithKline, Kyowa Hakko Kirin, EPS Corporation, Daiichi-Sankyo, IQVIA Services Japan/Quintiles, Pfizer Japan, Bayer Yakuhin, Otsuka, PRA Health Sciences, Merck Biopharma, Covance Japan, Medical Research Support, Sanofi, Syneos Health, Pfizer R&D Japan, PPD-SNBL, and Japan Clinical Research Operations; consulting or advisor role for Astellas, Pfizer Japan, Takeda, KYORIN, Eli Lilly Japan, and Ono. TM declares honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai, MSD, Nippon Boehringer Ingelheim, Novartis, Ono, Pfizer, Taiho, Takeda, Amgen, Invitae, Merck Biopharma, Thermo Fisher Scientific, and Eli Lilly; research grants from Daiichi-Sankyo, MSD, Nippon Boehringer Ingelheim, Chugai, Ono, Taiho, Ethicon, and Bridge Biotherapeutics. NY declares consulting fees from Chugai, honoraria or personal fees from MSD, AstraZeneca, Ono, Thermo Fisher Scientific, Daiichi-Sankyo, Taiho, Takeda, Chugai, Eli Lilly Japan, Boehringer Ingelheim, Novartis, Pfizer, BMS, Nippon Kayaku, GlaxoSmithKline, Sanofi, Hisamitsu, and Merck Biopharma; data safety monitoring board or advisory board participation for MSD, AstraZeneca, Ono, Taiho, Takeda, Chugai, Eli Lilly Japan, Boehringer Ingelheim, Novartis, Pfizer, BMS, Life Technologies Japan, Nippon Kayaku, Amgen, Guardant Health Japan, and Janssen; leadership or fiduciary role in The Japan Lung Cancer Society, Japanese Association of Supportive Care in Cancer, and West Japan Oncology Group. TA , TY , and ST are employees of Chugai. TT declares honoraria, personal fees, and grants from Chugai, Taiho, Eli Lilly, Ono, Nippon Boehringer Ingelheim, BMS, Daiichi-Sankyo, Eisai, Yakult Honsha, Novartis, Astellas, MSD, Nippon Kayaku, Kyowa Kirin, and CMIC ShiftZero. Publisher Copyright: © 2022 The Authors
PY - 2022/8
Y1 - 2022/8
N2 - Background: Mature progression-free survival (PFS) data from the phase III J-ALEX study showed superiority for alectinib versus crizotinib [hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.26-0.52; median PFS 34.1 versus 10.2 months, respectively] in advanced ALK (anaplastic lymphoma kinase)-positive non-small-cell lung cancer (NSCLC). Overall survival (OS) data were immature (HR 0.80, 99.8799% CI 0.35-1.82) at the time of data cut-off (30 June 2018). We report final OS data after ≥5 years of follow-up. Patients and methods: ALK inhibitor naive Japanese patients who were chemotherapy naive or had received one prior chemotherapy regimen were enrolled. Patients were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was independent review facility-assessed PFS, with OS (not fully powered) as a secondary endpoint. Results: Median duration of OS follow-up was 68.6 months with alectinib and 68.0 months with crizotinib. Treatment with alectinib did not prolong OS relative to crizotinib (HR 1.03, 95.0405% CI 0.67-1.58; P = 0.9105). Five-year OS rates were 60.9% (95% CI 51.4-70.3) with alectinib and 64.1% (95% CI 54.9-73.4) with crizotinib. In total, 91.3% (n = 95/104) of crizotinib-treated patients and 46.6% (n = 48/103) of alectinib-treated patients received at least one subsequent anticancer therapy. After study drug discontinuation, 78.8% of patients in the crizotinib arm switched to alectinib, while 10.7% of patients in the alectinib arm switched to crizotinib as a first subsequent anticancer therapy. Patients randomized to crizotinib tended to switch treatment earlier than those randomized to alectinib. Conclusion: Final OS analysis from J-ALEX did not show superiority of alectinib to crizotinib; this result was most likely confounded by treatment crossover. Alectinib remains a standard of care for the treatment of patients with advanced ALK-positive NSCLC.
AB - Background: Mature progression-free survival (PFS) data from the phase III J-ALEX study showed superiority for alectinib versus crizotinib [hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.26-0.52; median PFS 34.1 versus 10.2 months, respectively] in advanced ALK (anaplastic lymphoma kinase)-positive non-small-cell lung cancer (NSCLC). Overall survival (OS) data were immature (HR 0.80, 99.8799% CI 0.35-1.82) at the time of data cut-off (30 June 2018). We report final OS data after ≥5 years of follow-up. Patients and methods: ALK inhibitor naive Japanese patients who were chemotherapy naive or had received one prior chemotherapy regimen were enrolled. Patients were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was independent review facility-assessed PFS, with OS (not fully powered) as a secondary endpoint. Results: Median duration of OS follow-up was 68.6 months with alectinib and 68.0 months with crizotinib. Treatment with alectinib did not prolong OS relative to crizotinib (HR 1.03, 95.0405% CI 0.67-1.58; P = 0.9105). Five-year OS rates were 60.9% (95% CI 51.4-70.3) with alectinib and 64.1% (95% CI 54.9-73.4) with crizotinib. In total, 91.3% (n = 95/104) of crizotinib-treated patients and 46.6% (n = 48/103) of alectinib-treated patients received at least one subsequent anticancer therapy. After study drug discontinuation, 78.8% of patients in the crizotinib arm switched to alectinib, while 10.7% of patients in the alectinib arm switched to crizotinib as a first subsequent anticancer therapy. Patients randomized to crizotinib tended to switch treatment earlier than those randomized to alectinib. Conclusion: Final OS analysis from J-ALEX did not show superiority of alectinib to crizotinib; this result was most likely confounded by treatment crossover. Alectinib remains a standard of care for the treatment of patients with advanced ALK-positive NSCLC.
KW - alectinib
KW - ALK-positive NSCLC
KW - crizotinib
KW - J-ALEX
KW - overall survival
UR - http://www.scopus.com/inward/record.url?scp=85134342264&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85134342264&partnerID=8YFLogxK
U2 - 10.1016/j.esmoop.2022.100527
DO - 10.1016/j.esmoop.2022.100527
M3 - Article
C2 - 35843080
AN - SCOPUS:85134342264
SN - 2059-7029
VL - 7
JO - ESMO Open
JF - ESMO Open
IS - 4
M1 - 100527
ER -