PD-L1 expression, tumor mutation burden and response to immune checkpoint blockade in patients with HER2-mutant lung cancers.

Abstract

9060 Background: HER2 mutations are present in 3% of lung cancers. Response to immune checkpoint blockade (ICB) in this subset of lung cancers is unknown. We evaluate the landscape of PD-L1 and tumor mutation burden (TMB) in HER2-mutant lung cancers (HER2m) and their response to ICB. Methods: Patients (pts) with advanced HER2m were identified retrospectively. PD-L1 expression was determined by immunohistochemistry (IHC); TMB was estimated by next-generation sequencing (NGS) using MSK-IMPACT. Objective response rate (ORR) to ICB was determined using RECIST v1.1. Kaplan-Meier was used for PFS and OS analyses. Results: We identified 122 pts with HER2m, of whom 87 had PD-L1 IHC and 84 had NGS. 26 pts with known activating mutations in HER2m were treated with ICB. PD-L1 expression was < 1% in 67 (77%), 1-49% in 9 (10%), and ≥50% in 11 (13%) pts. PD-L1 expression was lower when compared to an unselected cohort (n = 578) of lung cancers profiled at our center (p = 0.006). Median TMB (5.7 Mt/Mb, range 0.8-91.8) was the same as the median TMB of an unselected cohort (n = 3000) of lung cancers (p = 0.21). In those treated with ICB, ORR was 12% (3/26, 95% CI 3-30%), including 3 PR, 8 SD, 15 PD. In the 3 responders: none had an HER2 YVMA mutation; 2 (66%) had PD-L1 ≥50%; 2 (66%) had TMB ≥median; median response duration was 3.4 months (range 1.4-21.2); and 1 (33%) remained on treatment with PR. From the start of ICB, median PFS was 1.9 months (95% CI 1.5-4.0), and median OS was 10.4 months (95% CI 5.9-NR). Conclusions: In pts with HER2-mutant lung cancers, PD-L1 expression is lower but TMB is similar to unselected lung cancers. Response to PD-(L)1 blockade is uncommon in pts with HER2-mutant lung cancers, but treatment with ICB can still be considered, particularly in the context of high PD-L1 expression or higher TMB.