Good responses to first-line immunotherapy-included treatment in lung squamous carcinoma with rare driver gene mutations: a report of three cases.

Background: In terms of treatment, non-small cell lung cancer (NSCLC) can be classified into driver gene mutation-positive or -negative lung cancer. Compared with adenocarcinoma, lung squamous carcinoma (LUSC) patients with rare driver gene mutations are a small proportion of NSCLC, who experience significantly less benefit from targeted therapies and have limited second-line treatment options and poor prognosis. Immunotherapy is an important treatment strategy for patients with NSCLC. In clinical practice, LUSC patients could receive immunotherapy regardless of the patient's gene mutation status and gene mutation detection is not recommended for LUSC patients for first-line treatment decision. Therefore, there is little data on the efficacy of first-line immunotherapy-included treatments in LUSC with rare driver gene mutations, which deserves to be collected and reported.

Case description: In this study, we report three female patients, aged from 28 to 65 years with stage IIIA-IVB LUSC and rare driver gene mutations, including epidermal growth factor receptor (EGFR) exon 18 point mutation G719X/S768I, EGFR exon 20 insertion, and echinoderm microtubule associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion, respectively. All three patients received first-line immunotherapy in combination with chemotherapy and achieved notable treatment outcomes. Case 1 achieved pathologic complete response (CR) after two cycles of immunochemotherapy, followed by a disease-free survival (DFS) of at least 30 months. Case 2 underwent four cycles of immunochemotherapy and rapidly achieved partial response (PR), followed by 2 years of monoimmunotherapy, with a progression-free survival (PFS) of at least 68 months. In case 3, except the primary lesion, there were CR for all metastatic lesions after 2 cycles of immunochemotherapy. These lesions remained absent in the subsequent 8 months until salvage surgery was performed and the DFS was at least 24 months.

Conclusions: These findings suggested that first-line immunotherapy-included treatment may provide promising survival benefits for LUSC patients with rare driver gene mutations.