Li Jixian, Zhan Xiang, Shao Mengqing, Zeng Renya, Li Jianan, Zhu Hui, Feng Alei, Yang Zhe, Jing Wang
Shandong Provincial Hospital, Shandong University, Jinan City, 250021, Shandong Province, China.
Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Jinan City, 250021, Shandong Province, China.
Sci Rep. 2025 Jul 1;15(1):20952. doi: 10.1038/s41598-025-03422-9.
Osimertinib is the standard first-line options for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). Co-mutations in TP53 results in poor survival for patients. However, the studies on treatment options and clinical outcomes of patients with EGFR-TP53 co- mutation are limited. Patients with EGFR mutation-positive locally advanced or metastatic NSCLC carrying TP53 mutations were recruited from two institutions and randomly allocated into two groups, either receiving osimertinib plus chemotherapy (Osi + Chemo group) or osimertinib monotherapy (Osi group). The progression-free survival (PFS) was evaluated as the primary endpoint and the response was also assessed. Between January 2020 and August 2023, ninety-eight patients were enrolled with 47 and 51 patients receiving combination therapy and the monotherapy. After a median follow-up of 19.2 months, overall response rate (ORR) was 80.0% vs. 71.7% (p = 0.36), favoring Osi + Chemo group, as well as in disease control rate (DCR) (91.4% vs. 80.4%, p = 0.45). The median PFS in the Osi + Chemo group was 26.0 months versus 20.7 months in the Osi group, but there was no significant difference (p = 0.34). The subgroup analysis indicated that for patients with L858R mutation, Osi + Chemo therapy significantly prolonged the median PFS (not reached [NR] versus 17.1 months, p = 0.03), but showed no benefit in patients with 19Del (20.6 months versus NR, p = 0.31). Osimertinib plus chemotherapy has a tendency to increase ORR and prolong PFS in NSCLC with EGFR and TP53 co-mutations, particularly in patients with L858R mutation.
奥希替尼是晚期表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的标准一线治疗选择。TP53基因共突变会导致患者生存率降低。然而，关于EGFR-TP53共突变患者的治疗选择和临床结局的研究有限。从两家机构招募携带TP53突变的EGFR突变阳性局部晚期或转移性NSCLC患者，并随机分为两组，分别接受奥希替尼联合化疗（奥希替尼+化疗组）或奥希替尼单药治疗（奥希替尼组）。将无进展生存期（PFS）作为主要终点进行评估，并对疗效进行评估。在2020年1月至2023年8月期间，共纳入98例患者，其中47例接受联合治疗，51例接受单药治疗。中位随访19.2个月后，奥希替尼+化疗组的总缓解率（ORR）为80.0%，奥希替尼组为71.7%（p = 0.36），奥希替尼+化疗组更具优势，疾病控制率（DCR）也是如此（91.4%对80.4%，p = 0.45）。奥希替尼+化疗组的中位PFS为26.0个月，奥希替尼组为20.7个月，但差异无统计学意义（p = 0.34）。亚组分析表明，对于L858R突变患者，奥希替尼+化疗显著延长了中位PFS（未达到[NR]对17.1个月，p = 0.03），但对19号外显子缺失（Del）患者无益处（20.6个月对NR，p = 0.31）。奥希替尼联合化疗有提高EGFR和TP53共突变NSCLC患者的ORR并延长PFS的趋势，尤其是L858R突变患者。
