Afatinib for the Treatment of Non-Small Cell Lung Cancer Harboring Uncommon

Previously, we developed a database of 693 patients with NSCLC and uncommon Patients were identified from a prospective database developed by Boehringer Ingelheim and Of 1023 patients included, 587 patients were EGFR TKI-naïve and 425 were EGFR TKI-pretreated. The distribution of mutation categories was: major uncommon (41.4%); exon 20 insertions (22.3%); T790M (20.3%); and 'others' (15.9%); 38.6% had compound mutations. Overall, median TTF (TKI naïve/pretreated) was 10.7 and 4.5 months. ORR was 49.8% and 26.8%, respectively. In TKI-naïve patients, afatinib demonstrated activity against major uncommon mutations (median TTF: 12.6 months; ORR: 59.0%), 'other' mutations (median TTF: 10.7 months; ORR: 63.9%) including strong activity against E709X (11.4 months; 84.6%) and L747X (14.7 months; 80.0%), and compound mutations (11.5 months; 63.9%). Although sample sizes were small, notable activity was observed against specific exon 20 insertions at residues A763, M766, N771, and V769, and against osimertinib resistance mutations (G724S, L718X, C797S). Afatinib should be considered as a first-line treatment option for NSCLC patients with major uncommon, compound, 'other' (including E709X and L747X) and some specific exon 20 insertion mutations. Moderate activity was seen against osimertinib resistance

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Copyright © 2022 Yang, Schuler, Popat, Miura, Park, Passaro, De Marinis, Solca, Märten and Kim.

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JC-HY reports personal and/or institutional fees from Amgen; personal and institutional fees from AstraZeneca, Boehringer Ingelheim, Novartis, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals; institutional fees from Bayer, Daiichi Sankyo, Eli Lilly, Merck KGaA (Darmstadt, Germany), Merck Sharp & Dohme, JNJ; personal fees from Bristol Myers Squibb, Ono Pharmaceuticals, Pfizer; grants from AstraZeneca. MS reports consultancy fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda; honoraria for CME presentations from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Novartis; research funding from AstraZeneca, Bristol Myers Squibb. SP has received grant support, honoraria, consulting fees, and travel support from Boehringer Ingelheim; consulting fees and travel support from Bristol Myers Squibb; honoraria and consulting fees from Roche, Takeda, AstraZeneca; honoraria from Chugai Pharma; consulting fees from Novartis, Guardant Health, AbbVie, Pfizer; and consulting fees and travel support from Merck Sharp & Dohme. SM has received honoraria from Chugai Pharma, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bristol Myers Squibb, Taiho Pharma, Pfizer. KP has received personal fees from Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Eli Lilly, Hanmi, Kyowa Hakko Kirin, Incyte, LOXO, Merck KGaA, Merck Sharp & Dohme, Ono Pharmaceuticals, Novartis, and Roche; and research funding from AstraZeneca and Merck Sharp & Dohme. AP received honoraria for consulting, advisory role or lectures from AstraZeneca, Agilent/Dako, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Jansenn, Merck Sharp & Dohme, Pfizer and Roche Genentech. FDM has received honoraria or consulting fees from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme and Roche. FS and AM are employees of Boehringer Ingelheim. EK has received personal fees from Boehringer Ingelheim, AstraZeneca, and Genentech. The authors declare that this study received funding from Boehringer Ingelheim. The sponsors played a role in the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication and as such are included in the author list.