Background: EGFR TKIs are established as an effective treatment (tx) option for pts with EGFRm+ NSCLC harboring common (Del19 or L858R) mutations, but limited clinical data exist for EGFR TKI use in the 7–23% of NSCLC tumors with uncommon EGFR mutations.1

Methods: In this non-interventional, global, multi-center study (NCT04179890), existing medical or electronic health records were identified for consecutive EGFR TKI-naïve pts with NSCLC harboring uncommon EGFR mutations treated with either erlotinib, gefitinib, afatinib or osimertinib. Endpoints included time to tx failure (TTF), overall response rate (ORR), overall survival (OS), and duration of response (DoR).

Results: Pts (n=246; median age: 69.5 yrs; brain metastases: 7%; ECOG PS ≥2: 16%; Asian: 84%) were recruited from nine countries. Uncommon mutation categories were: major uncommon (G719X, L861Q, S768I; 73%); compound (35%); ex20ins (12%); T790M (7%); other (9%). Most pts (n=226; 92%) were treated in 1st-line with an EGFR TKI; 132 (54%), 70 (28%), 35 (14%), and 7 (3%) received afatinib, gefitinib, erlotinib, and osimertinib. 57% of pts received >1 line of therapy. Mutations were detected using PCR (75%) or sequencing (25%), mainly based on tissue biopsy (86%). Pathology reports varied in quality, often lacking detail on specific mutations, e.g. ‘ex18' or ‘ex20ins'. Overall, median TTF with an EGFR TKI was 9.9 mos; afatinib: 11.3 mos; gefitinib: 9.2 mos; erlotinib: 8.2 mos. Overall median OS was 24.4 mos. In pts with major uncommon mutations, median TTF was 14.3 and 9.8 mos with afatinib and 1st-gen TKIs. Median TTF in pts receiving 1st-line chemotherapy was only 4.0 mos. ORR was 42% overall (major: 50%; compound: 49%; other: 44%; T790M: 20%; ex20ins: 17%); afatinib: 44% (DoR: 12.0 mos); 1st-gen TKIs: 44% (DoR: 11.0 mos). More detailed analysis will be presented at the conference, including further details of outcomes in pts with specific uncommon mutations (e.g. specific ex20ins).

Conclusions: EGFR TKIs were the preferred tx option in pts with NSCLC harboring uncommon EGFR mutations. Response was highest in pts with major uncommon, and/or compound mutations. Data were in line with recent analyses of afatinib in uncommon mutations. Tx with an EGFR TKI should be considered as standard for pts with uncommon mutations, although many with ex20ins were not responsive. To inform optimal tx choice, specific details of EGFR mutations must be reported.

References: 1.Yang JC, et al. J Thorac Oncol 2020;15:803–15

Citation Format: Satoru Miura, Te-Chun Hsia, Jen-Yu Hung, Hyun Ae Jung, Jin-Yuan Shih, Tsung-Ying Yang, Cheol-Kyu Park, Seung Hyeun Lee, Tatsuro Okamoto, Hee Kyung Ahn, Yong Chul Lee, Yuki Sato, Sung Sook Lee, Céline Mascaux, Hasan Daoud, Angela Märten, Sanjay Popat. UpSwinG: real-world, non-interventional cohort study on TKI activity in patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC with uncommon mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB138.