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. 2022 Aug 22:15:873-882.
doi: 10.2147/OTT.S362535. eCollection 2022.

Sequential Afatinib and Osimertinib in Asian Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer and Acquired T790M: Combined Analysis of Two Global Non-Interventional Studies

Satoru Miura  1 , Hyun Ae Jung  2 , Shin Yup Lee  3 , Seung Hyeun Lee  4 , Min Ki Lee  5 , Yong Chul Lee  6 , Maximilian J Hochmair  7 , Cheng-Ta Yang  8 , Angela Märten  9 , James Chih-Hsin Yang  10 , Sanjay Popat  11   12
Affiliations

Sequential Afatinib and Osimertinib in Asian Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer and Acquired T790M: Combined Analysis of Two Global Non-Interventional Studies

Satoru Miura et al. Onco Targets Ther. .

Abstract

Objective: Two recent non-interventional trials, GioTag and UpSwinG, demonstrated encouraging time-to-treatment failure (TTF) and overall survival (OS) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) (Del19 or L858R) who received sequential afatinib/osimertinib, especially in Asians. Here, we have undertaken a combined analysis of Asian patients from both studies.

Materials and methods: Existing medical/electronic records were identified for consecutive EGFR-tyrosine kinase inhibitor (TKI)-naïve patients who received first-line afatinib/second-line osimertinib in "real-world" practice (all T790M-positive). Patients with active brain metastases were excluded. The primary objective was TTF. OS was a key secondary objective.

Results: One hundred and sixty-eight patients were analyzed. Most patients were recruited from South Korea or Japan (52/21%). At the start of afatinib, median age (range) was 61.5 years (35-88), 58% were female, Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0/1/≥2) was 29/62/9%, 17% had brain metastases, and EGFR mutation status (Del19/L858R) was 65/35%. At the start of osimertinib, ECOG PS (0/1/≥2) was 22/61/17% and 14% had brain metastases. Median TTF and OS were 30.0 months (95% CI: 24.5-32.5) and 45.2 months (95% CI: 41.7-71.1), respectively. Median OS was 63.5 months in patients with a Del19 mutation. Median OS in patients with brain metastases or ECOG PS ≥2 was 26.4 and 33.1 months, respectively.

Conclusion: Sequential afatinib/osimertinib showed encouraging activity in Asian patients with EGFR mutation-positive NSCLC and T790M-mediated acquired resistance, especially those with Del19-positive disease. Activity was observed across "real-world" patients including those with poor ECOG PS and/or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib.

Keywords: EGFR; T790M; afatinib; osimertinib; sequential.

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Conflict of interest statement

SM reports receiving honoraria from Chugai Pharma, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bristol Myers Squibb, Taiho Pharma, and Pfizer. HAJ, SYL, SHL, MKL, and YCL declare no potential conflict of interest. MJH reports receiving consulting fees from Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Novartis, Roche, and honoraria from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche. C-TY declares no potential conflict of interest. AM declares employment with Boehringer Ingelheim. JC-HY reports receiving 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, Johnson & Johnson; personal fees from Bristol Myers Squibb, Ono Pharmaceuticals, Pfizer; grants from AstraZeneca. SP reports receiving 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; consulting fees and travel support from Merck Sharp & Dohme.

Figures

None
Graphical abstract
Figure 1
Figure 1
TTF (A) and OS (B) in Asian patients receiving sequential Afatinib and osimertinib (n = 168).
Figure 2
Figure 2
TTF (A) and OS (B) in Asian patients receiving sequential Afatinib and osimertinib according to EGFR mutation type (Del19 or L858R).
See this image and copyright information in PMC

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