Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan
Satoru Miura , Te-Chun Hsia , Jen-Yu Hung , Hyun Ae Jung , Jin-Yuan Shih , Cheol-Kyu Park , Seung Hyeun Lee , Tatsuro Okamoto , Hee Kyung Ahn , Yong Chul Lee , Yuki Sato , Sung Sook Lee , Celine Mascaux , Hasan Daoud , Angela Maerten , Sanjay Popat
Background: EGFR TKIs are an established treatment (tx) option for pts with EGFR mutation-positive NSCLC with common mutations (Del19 or L858R); however, 7–23% of NSCLC tumors harbor uncommon EGFR mutations, where EGFR TKI efficacy is less established. These mutations are highly heterogeneous, and developments in detection by NGS are helping to identify mutations with little or no clinical data. 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 uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q or S768I], ‘other’ or compound mutations) treated with erlotinib, gefitinib, afatinib, osimertinib or other systemic therapy. Endpoints were time to tx failure (TTF), ORR, OS and duration of response (DoR). Results: Overall, 246 pts (median age: 69.5 yrs; Asian: 84%; brain metastases: 8%; ECOG PS ≥2: 16%) were recruited from 9 countries. Most pts (n=226; 92%) received an EGFR TKI as 1st-line therapy; 132 (54%), 105 (43%) and 7 (3%) received afatinib, 1st-gen TKIs and osimertinib, respectively. 57% of pts received >1 line of therapy. Most pts (73%) had a major uncommon mutation, 9% had other mutations and 33% had a compound mutation; these 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. 21% of ex18 and 72% of ex20ins were undefined. Median TTF and OS with EGFR TKIs were 9.9 and 24.4 mos; ORR was 42%. In pts treated with 1st-line chemotherapy (n=20), median TTF and ORR were 6.6 mos and 41%. Outcomes were most favorable in major uncommon and compound mutations (Table). TTF appeared to be higher with afatinib vs 1st-gen EGFR TKIs. In most mutation categories, median OS was >2 yrs, possibly reflecting high subsequent therapy uptake. Conclusions: In a real-world setting, EGFR TKIs were the preferred tx option in pts with uncommon EGFR mutations; strongest outcomes were seen in major uncommon and compound mutations, and in pts treated with afatinib. Data were in line with recent analyses of afatinib in uncommon mutations. Tx with an EGFR TKI should be considered as standard for most pts with uncommon mutations. Optimal tx for pts with uncommon mutations requires improvements in pathology reports, with more emphasis on NGS methodology and precise definition of mutations. Clinical trial information: NCT04179890
Pts treated with afatinib | Median TTF, mos | Median OS, mos | ORR, % | Median DoR, mos |
---|---|---|---|---|
All (n=132) | 11.3 | 24.5 | 44 | 12.0 |
Major uncommon (n=94) | 14.3 | 24.5 | 51 | 12.0 |
Compound (n=46) | 12.6 | 23.4 | 53 | 10.0 |
Other (n=9) | 10.8 | 20.2 | 29 | 10.5 |
Ex20ins (n=18) | 8.4 | 22.5 | 19 | 5.5 |
Pts treated with 1st-gen EGFR TKI | ||||
All (n=106) | 8.8 | 24.2 | 44 | 6.0 |
Major uncommon (n=80) | 9.8 | 28.5 | 47 | 6.5 |
Compound (n=32) | 12.4 | 31.3 | 48 | 6.0 |
Other (n=12) | 7.3 | 12.8 | 56 | 4.5 |
Ex20ins (n=10) | 5.2 | 21.0 | 17 | 33.0 |
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2023 ASCO Annual Meeting
First Author: Min Hee Hong
2023 ASCO Annual Meeting
First Author: Yong Won Choi
2023 ASCO Annual Meeting
First Author: Xiuning Le
2023 ASCO Annual Meeting
First Author: Amin Nassar