Abstract 643P
Background
1L alectinib has improved outcomes in pts with ALK+ NSCLC. Real-world data on resistance mechanisms to alectinib and the efficacy of 1L alectinib in a large cohort are limited. ALCURE is a real-world, observational, multicenter study exploring resistance mechanisms to alectinib, efficacy of 1L alectinib and treatment sequences in Japanese pts with advanced ALK+ NSCLC. We present the second interim analysis data for ALCURE.
Methods
On-label first-line alectinib was initiated before (cohort A) or after (cohort B) enrollment in clinical practice. Blood/tissue samples, at baseline and at disease progression, were analyzed by targeted resequencing.
Results
From Jan 2020 to Nov 2020, 200 pts in cohort A and 49 pts in cohort B were enrolled from 28 sites (data cutoff 6 Nov 2023). In cohorts A/B: median age, 65/56 years; female, 60%/57%; smoking history, 36%/33%; brain metastases, 22%/31%. Tissue samples from 159 (80%) pts in cohort A and 39 (80%) pts in cohort B were sequenced: EML4-ALK variant 1 (V1) was the most common variant (cohort A: 51%; cohort B: 41%). At baseline in cohort B (N=49), TP53 mutations were detected in 19 pts (39%). The median treatment duration of 1L alectinib before enrollment in cohort A was 24.0 months (range 1.0–110.7). Median progression-free survival (mPFS): 102.4 mos (95% CI 83.7–not reached [NR]) in cohort A and 28.2 mos (95% CI 11.8–38.5) in cohort B. mPFS (EML4-ALK V1/V3a&b) was 102.4/NR mos in cohort A, 34.3/20.0 mos in cohort B. mPFS was 34.3 months in TP53 wild-type and 13.3 mos in TP53 mutated in cohort B. Samples refractory to alectinib were sequenced from 53 pts (cohort A) and 21 pts (cohort B); 12 pts (23%) and 3 (14%) pts had secondary ALK mutations including G1202R or I1171N. mPFS in pts with/without secondary mutations was 14.6/36.6 mos (cohort A).
Conclusions
Real-world efficacy data of 1L alectinib were consistent with clinical trial data. The results from cohort A should be interpreted with caution as the pts who had discontinued alectinib in a short period of time were not included. Pts with TP53 WT had longer PFS with alectinib than pts with TP53 mutations. Pts with secondary ALK mutations at progression had shorter PFS with alectinib than those without.
Clinical trial identification
UMIN000038934.
Editorial acknowledgement
This study is sponsored by Chugai Pharmaceutical Co., Ltd. Third-party medical writing assistance, under the direction of the authors, was provided by Tahmina S. Alam, MA, of Ashfield MedComms, an Inizio company, and was funded by Chugai Pharmaceutical Co., Ltd.
Legal entity responsible for the study
Chugai Pharmaceutical Co., Ltd.
Funding
Chugai Pharmaceutical Co., Ltd.
Disclosure
A. Mouri: Financial Interests, Personal, Speaker’s Bureau: Chugai pharmaceutical Co. Ltd, AstraZeneca, Ono Pharmaceutical Co. Ltd. T. Tsuda: Financial Interests, Personal, Research Funding: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Speaker, Consultant, Advisor: Chugai Pharmaceutical Co., Ltd. M. Oki: Financial Interests, Institutional, Speaker’s Bureau: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Sponsor/Funding: Chugai Pharmaceutical Co., Ltd. E. Ichihara: Financial Interests, Personal, Speaker’s Bureau: Janssen Pharmaceutical K.K., Pfizer, Bristol Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Chugai Pharmaceutical, AstraZeneca K.K., Novartis, Eli Lilly Japan K.K., Boehringer Ingelheim; Financial Interests, Institutional, Research Funding: Janssen Pharmaceutical K.K.; Non-Financial Interests, Institutional, Research Funding: Janssen Pharmaceutical K.K. H. Tanaka: Financial Interests, Institutional, Local PI: Chugai Pharmaceutical, Pfizer, Takeda Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical, Pfizer, Takeda Pharmaceutical. K. Azuma: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca K.K., MSD, Ono Pharma, Chugai Pharma, Bristol Myers Squibb, Takeda Pharma. S. Kuyama: Financial Interests, Personal, Speaker, Consultant, Advisor: Chugai Pharmaceutical Co., Ltd. H. Akamatsu: Financial Interests, Personal, Advisory Board: Amgen Inc., Janssen Pharmaceutical K.K., GSK, Sandoz; Financial Interests, Personal, Research Funding: Amgen Inc., Chugai Pharmaceutical Co., Ltd., MSD K.K; Financial Interests, Personal, Speaker’s Bureau: Amgen Inc., AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Nippon Kayaku. Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K. K. Uchibori: Financial Interests, Personal, Advisory Board: AstraZeneca ; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, Chugai, Takeda Pharmaceutical, Ono Pharmaceutical, Novartis, Eli Lilly, Thermofisher, Bristol Myers Squibb, Merck, MSD, Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Amgen, Taiho Pharma, Pharma Mar S.A. H. Hayashi: Financial Interests, Personal, Research Grant, Grants/contracts: IQVIA Services JAPAN K.K., Eisai Co., Ltd., Syneos Health Clinical K.K., EP-CRSU Co., Ltd., EPS Corporation, Shionogi & Co., Ltd., Nippon Kayaku Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., GSK K.K, MSD K.K., Sanofi K.K, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bristol Myers Squibb Company, SRL Medisearch Inc., Janssen Pharmaceutical K.K., PRA Health Sciences Inc., CMIC Co., Ltd., Astellas Pharma Inc., Pfizer R&D Japan G.K., Ascent Development Services, Labcorp Development Japan K.K., Eisai Inc., Kobayashi Pharmaceutical Co., Ltd., Bayer Yakuhin Ltd., Pfizer Japan Inc., AstraZeneca K.K., AbbVie Inc., Daiichi Sankyo Co., Ltd., A2 Healthcare Corp., Novartis Pharma K.K., Eli Lilly Japan K.K., Merck Biopharma Co., Ltd., Medpace Japan K.K., Kyowa Kirin Co., Ltd., Japanese Gastric Cancer Association, Thoracic Oncology Research Group, Clinical Research Support Center Kyushu, West Japan Oncology Group, Japan Clinical Caner Research Organization, Comprehensive Support Project for Oncological Research of Breast Cancer, EPS International Co., Ltd., Mebix, Inc., Ono Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Medical Reserch Support; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria: Ono Pharmaceutical Co.,Ltd., Merck Biopharma Co., Ltd., Daiichi Sankyo Co., Ltd., 3H Clinical Trial Inc., AstraZeneca K.K., Novartis Pharma K.K., Chugai Pharmaceutical Co.,Ltd., Bristol Myers Squibb Company, Eli Lilly Japan K.K., Amgen Inc., MSD K.K., Sysmex Corporation, Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Janssen Pharmaceutical K.K., Guardant Health Japan Corp. E. Miyauchi: Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker, Consultant, Advisor: Chugai Pharmaceutical Co., Ltd. N. Ishizuka: Financial Interests, Personal, Financially compensated role: Chugai, Daiichi Sankyo. Y. Nakagawa: Financial Interests, Personal, Stocks/Shares: Chugai Pharmaceutical Co., Ltd. R. Katayama: Financial Interests, Institutional, Licencing Fees or royalty for IP: Eiken Chemical ; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, TOPPAN; Financial Interests, Institutional, Royalties: Eiken Chemical; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Chugai, MSD, Nippon Kayaku, Takeda, AstraZeneca. All other authors have declared no conflicts of interest.