Background: Genetic alternations of Epidermal growth factor receptor (EGFR) in lung cancer had shown associated with response or resistance to anti-PD-1 therapy. However, there is a lack of understanding of the clinical significance of EGFR mutation subtypes in non-squamous non-small cell lung cancer (NSCLC).

Methods: We retrospectively analyzed 510 patients with non-squamous NSCLC treated with anti-PD-(L)1 monotherapy from four independent cohorts. The tumor tissues from the patients were subjected to MSK-IMPACT panel target sequencing or whole exome sequencing. The association between clinical features and specific EGFR alterations was analyzed.

Results: EGFR positivity was 13.33% (68/510), which is close to the proportion in CheckMate-057 (14.09%), while is higher than in KEYNOTE-010 (8.33%). Compared with 68 EGFR alteration lung cancers, DCR, ORR and durable clinical benefit (DCB) were better in patients with EGFR wide-type (Chi-square test, p = 0.0021, 0.0436 and 0.0014, respectively), while the PFS and OS in EGFR wide-type group was not significantly longer than the EGFR positive group (Log-rank test, p =0.1310 for PFS and 0.7730 for OS). Among EGFR positivity, the incidence of L858R only, T790M only, L858R/T790M mixed and others were 23.53%, 19.12%, 11.76% and 45.59%, respectively. A significant difference in survival among the four subtypes of EGFR positive group was observed, mutation of T790M only showed a worse PFS and OS probability compared to the other subtypes (p<0.001 and p = 0.002), whereas mutation of L858R only showed a poorer PFS (p=0.05).

Conclusion: Mutation of T790M in non-squamous NSCLC prospects worse survival than other EGFR mutations, while mutation of non-L858R and non-T790M subtypes was not a worse factor than EGFR wide-type group. The heterogeneity of EGFR alternations may be beneficial for establishing the uses of PD-(L)1 therapies for lung cancers.

Citation Format: Haibo Tang, Xiaoning Li, Wenzhuan Xie, Mengli Huang. Effects on immunotherapy of EGFR mutation subtypes in non-squamous NSCLC [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 379.