1110P Clinical outcomes for EGFR/HER2 exon 20 insertion-mutated NSCLC

Abstract

EGFR and HER2 exon 20 insertion mutations (ex20ins) are rare in NSCLC, with poor prognosis and few targeted therapy options. There are limited real-world data for patients (pts) with these uncommon mutations. We report clinicopathologic features and outcomes for 131 pts with ex20ins NSCLC across British Columbia, Canada. NSCLC pts who had tumour testing Jan 1, 2016-Dec 31, 2021 (n=7233) were identified via the provincial database. Pts with ex20ins in EGFR or HER2 were included. Survival analyses were performed using the Kaplan-Meier method with log-rank testing. Of 131 pts (84 EGFR, 47 HER2), 46% were Asian, 60% female, 71% never/light smokers (Table). 85% were metastatic (met). For met EGFR ex20ins pts (n=71), median overall survival (mOS) was 7.1 months (mos). 39/71 (55%) had systemic therapy (ST); 20/39 (51%) received ex20ins-specific tyrosine kinase inhibitor (TKI), (eg. poziotinib, mobocertinib, or afatinib). mOS was 18.6 mos for pts receiving any ST vs 2.6 mos for pts who did not (p<0.001). mOS was similar for pts treated with ex20ins TKI vs other (18.6 vs 15.9 mos, p=0.463). In 1st-line, mPFS was 7.1 mos for all pts; mPFS was 4.1 vs. 7.4 mos for TKI-treated pts vs other (p=0.744). Gr 3 toxicity was 15.4% (6/39) for all ST pts, and 20% (4/20) for TKI pts. For met HER2 ex20ins pts (n=41), mOS was 7.3 mos. 25/41 (61%) pts had ST; 11/25 (44%) received ex20ins-specific TKI. mOS was 9 mos for pts who received any ST vs 4.9 mos for pts who did not (P=0.015). mOS was 23.0 mos for pts treated with ex20ins TKI vs 5.6 mos for pts who were not (P=0.019). In the 1L setting mPFS was 4.5 mos for all pts who had ST; mPFS was 5.4 vs. 2.1 mos for pts who had TKI vs other (P=0.343). Gr 3 toxicity was 16% (4/25) for all ST pts, and 9% (1/11) for TKI pts.Table: 1110PEGFR (n=84)HER2 (n=47)Age (y), median (range)66 (37-87)67 (27-97)Sex, n (%)M33 (39)20 (43)F51 (61)27 (57)Ethnicity, n (%)Asian41 (49)19 (40)Non-Asian43 (51)28 (60)Smoking (pack years), n (%)Never47 (56)26 (55)Light (</=10)16 (19)4 (9)Heavy (>10)21 (25)15 (32)Unknown0 (0)2 (4)Brain mets, n (%)31 (37)12 (26)Palliative systemic therapy (ST), n (%)Total39 (46)25 (53)No. lines. Median (range)1 (0-5)1 (0-5)Ex20ins TKI20 (24)11 (23)Immunotherapy15 (19)17 (36)Treatment outcomesOS median (range) mosAll pts7.1 (0.9-83.2)7.3 (0.5-56.7)ST18.6 (3.7-83.2)9.0 (1.5-56.7)No ST2.6 (0.9-26.4)4.9 (0.5-14.6)ex20ins TKI18.6 (3.7-28.8)23.0 (3.3-56.7)Other ST15.9 (4.7-83.2)5.6 (1.5-17.1) Open table in a new tab In this large, population-based retrospective review of EGFR and HER2 ex20ins NSCLC pts, there was improvement in survival for met pts who received any ST vs. those who did not. Among HER2 ex20 pts who received ST, overall survival was significantly better for those who received ex20ins-specific TKIs.