Immunotherapy effectiveness and optimal combination strategy in lung cancers with EGFR uncommon and 20ins mutations was unclear. Based on 627 lung adenocarcinoma patients harboring EGFR mutations and receiving immunotherapy, we reported that patients with EGFR uncommon mutations had better response to immunotherapy, than EGFR 19del/L858R or 20in mutations. Immunotherapy monotherapy or plus chemotherapy was identified as better combination strategy for EGFR uncommon or 20ins mutations, respectively. Higher tumor mutation burden, more M1 macrophage, less Tregs and M2 macrophages infiltration, but not PD-L1 expression was found to be associated with EGFR uncommon mutations, compared to EGFR 19del/L858R or 20in mutations. These findings revealed diverse response and optimal combination strategy of lung adenocarcinoma patients harboring EGFR mutation subtypes, promoting rethinking about current immunotherapy application and prolonging survivals of them.

Inclusion Criteria:

1. age≥18 years,
2. advanced or recurrent LUAD confirmed by pathology,
3. harboring EGFR mutations confirmed by super amplification refractory mutation system (super-ARMS) or next-generation sequencing (NGS),
4. receiving anti-PD-(L)1 antibody therapy at least once,
5. Radiologically evaluable according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)

Exclusion Criteria:

-

EGFR-mutant LUAD patients receiving anti-PD-(L)1 therapies