针对 EGFR-TKI 治疗后进展的 EGFR 突变型非小细胞肺癌患者的免疫治疗方案。
Immunotherapy-based regimens for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR-TKI therapy.
机构信息
Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China.
Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China
出版信息
J Immunother Cancer. 2024 Apr 16;12(4):e008818. doi: 10.1136/jitc-2024-008818.
The sustained benefit of immunotherapy-based regimens in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after EGFR-tyrosine kinase inhibitor (TKI) failure is debatable. Neither Checkmate-722 nor Keynote-789 reached the prespecified statistical level of clinical benefit, but the ORIENT-31 and ATTLAS trials showed that the addition of a VEGF inhibitor to immunotherapy plus chemotherapy could significantly prolong survival. However, head-to-head comparisons of the efficacy of immunotherapy plus bevacizumab with chemotherapy versus that of immunotherapy with chemotherapy in this patient population are lacking. In addition, the critical question of who would benefit from an immunotherapy-based regimen remains unclear. We conducted an indirect comparative meta-analysis using chemotherapy as a common comparator to classify the relative efficacy of the two immunotherapy-based regimens. The indirect comparison showed that immunotherapy and bevacizumab plus chemotherapy had a significantly better progression-free survival (PFS) (HR=0.71, 95% CI 0.55 to 0.91) than immunotherapy plus chemotherapy. The EGFR mutation type and T790M mutation were found to be significantly associated with PFS of immunotherapy-based regimens. Compared with their counterparts, patients with L858R (HR 0.52, 95%CI 0.37 to 0.72), without T790M mutation (HR 0.50, 95% CI 0.35 to 0.71) tended to benefit significantly more from immunotherapy-based regimens. In conclusion, our findings support that the addition of VEGF inhibitor to immunotherapy and chemotherapy could be the preferred option for TKI-resistant, EGFR-mutated NSCLC, and that L858R mutation and T790M negativity could be identified as efficacy-associated factors for immunotherapy-based regimens.
免疫治疗联合方案在表皮生长因子受体(EGFR)突变型非小细胞肺癌(NSCLC)患者中,在 EGFR 酪氨酸激酶抑制剂(TKI)耐药后的持续获益存在争议。Checkmate-722 和 Keynote-789 研究均未达到预设的临床获益统计学水平,但 ORIENT-31 和 ATTLAS 研究表明,在免疫治疗联合化疗的基础上加用血管内皮生长因子(VEGF)抑制剂可显著延长生存。然而,在这一患者人群中,免疫治疗联合贝伐珠单抗与化疗相比,与免疫治疗联合化疗相比,免疫治疗联合方案的疗效尚无头对头比较。此外,谁将从免疫治疗方案中获益这一关键问题仍不清楚。我们采用化疗作为共同对照进行间接比较荟萃分析,以分类两种免疫治疗方案的相对疗效。间接比较显示,免疫治疗联合贝伐珠单抗与化疗相比,无进展生存期(PFS)(HR=0.71,95%CI 0.55 至 0.91)显著改善;免疫治疗联合化疗与免疫治疗联合化疗相比,PFS 也显著改善。EGFR 突变类型和 T790M 突变与免疫治疗方案的 PFS 显著相关。与对照组相比,L858R(HR 0.52,95%CI 0.37 至 0.72)和无 T790M 突变(HR 0.50,95%CI 0.35 至 0.71)患者可能从免疫治疗方案中获益更多。总之,我们的研究结果支持在免疫治疗联合化疗的基础上加用 VEGF 抑制剂可能是 EGFR-TKI 耐药的 EGFR 突变型 NSCLC 的首选方案,L858R 突变和 T790M 阴性可能是免疫治疗方案疗效相关的因素。