Tu Li, Liu Yanyang, Qiu Xiaoming, Liu Jiewei
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, China.
Transl Lung Cancer Res. 2025 Jun 30;14(6):2337-2346. doi: 10.21037/tlcr-2025-469. Epub 2025 Jun 26.
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.
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.
These findings suggested that first-line immunotherapy-included treatment may provide promising survival benefits for LUSC patients with rare driver gene mutations.
在治疗方面,非小细胞肺癌(NSCLC)可分为驱动基因突变阳性或阴性肺癌。与腺癌相比,驱动基因突变罕见的肺鳞状细胞癌(LUSC)患者在NSCLC中占比小,从靶向治疗中获益显著较少,二线治疗选择有限且预后较差。免疫疗法是NSCLC患者的重要治疗策略。在临床实践中,LUSC患者无论基因突变状态如何均可接受免疫治疗,且不建议对LUSC患者进行基因突变检测以用于一线治疗决策。因此,关于一线免疫治疗联合方案在驱动基因突变罕见的LUSC中的疗效数据很少,值得收集和报告。
在本研究中,我们报告了3例年龄在28至65岁之间的女性患者,她们患有IIIA-IVB期LUSC且驱动基因突变罕见,分别为表皮生长因子受体(EGFR)外显子18点突变G719X/S768I、EGFR外显子20插入以及棘皮动物微管相关蛋白样4(EML4)-间变性淋巴瘤激酶(ALK)融合。所有3例患者均接受了一线免疫治疗联合化疗,并取得了显著的治疗效果。病例1在两个周期的免疫化疗后达到病理完全缓解(CR),随后无病生存期(DFS)至少为30个月。病例2接受了四个周期的免疫化疗并迅速达到部分缓解(PR),随后进行了2年的单免疫治疗,无进展生存期(PFS)至少为68个月。在病例3中,经过两个周期的免疫化疗后,除原发灶外,所有转移灶均达到CR。在随后的8个月中这些病灶一直未出现,直到进行挽救性手术,DFS至少为24个月。
这些发现表明,一线免疫治疗联合方案可能为驱动基因突变罕见的LUSC患者提供有前景的生存获益。