Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Frankfurt, Germany.
Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Frankfurt, Germany.
Clin Lung Cancer. 2022 Nov;23(7):e473-e477. doi: 10.1016/j.cllc.2022.07.019. Epub 2022 Aug 10.
Tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR) like the third-generation TKI osimertinib have substantially improved the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring sensitizing EGFR mutations. However, there is a subset of patients that do not benefit from these therapies in terms of response rate or progression-free-survival (PFS). It has been shown that persistence of EGFR mutations in circulating tumor DNA (ctDNA) at weeks 3 and 6 after start of osimertinib predicts shorter PFS. These patients may benefit from additional chemotherapy. While combination therapies with older TKI have been demonstrated effective in improving outcome, they are associated with a significant increase in toxicity.
PACE-LUNG is a multicenter, single-arm, investigator initiated, phase II trial conducted with the German national Network Genomic Medicine (nNGM). Patients with stage IIIB or IV NSCLC and exon 19 deletion or p.L858R EGFR mutation not amenable to curative treatment with persisting ctDNA after 3 to 4 weeks of first-line osimertinib monotherapy will receive additional chemotherapy (4 cycles of either cisplatin/pemetrexed or carboplatin/pemetrexed). Afterwards, osimertinib will be continued as standard of care until disease progression or intolerable toxicity. The primary endpoint is PFS. Secondary endpoints include overall survival, response rate, safety, and quality of life. Concomitant translational research will be performed to identify patterns of mutational evolution in ctDNA upon disease progression or ctDNA persistence. Enrollment started in December 2021.
The PACE-LUNG trial is designed to evaluate the efficacy and safety of a biomarker-driven strategy for therapy escalation in patients at high risk for early treatment failure. This approach aims not only to improve treatment outcomes, but also to limit the anticipated additional toxicity to high-risk patients.
2019-004757-88 (EudraCT).
针对表皮生长因子受体（EGFR）的酪氨酸激酶抑制剂（TKI），如第三代 TKI 奥希替尼，显著改善了携带敏感 EGFR 突变的晚期非小细胞肺癌（NSCLC）患者的治疗效果。然而，有一部分患者在反应率或无进展生存期（PFS）方面并未从中受益。研究表明，奥希替尼治疗开始后 3 周和 6 周时循环肿瘤 DNA（ctDNA）中 EGFR 突变的持续存在可预测较短的 PFS。这些患者可能受益于额外的化疗。虽然与较老的 TKI 联合治疗已被证明能有效改善预后，但它们与毒性显著增加相关。
PACE-LUNG 是一项多中心、单臂、研究者发起的、由德国国家基因组医学网络（nNGM）进行的 II 期临床试验。IIIb 期或 IV 期 NSCLC 患者，携带无法通过一线奥希替尼单药治疗 3-4 周后持续存在 ctDNA 的外显子 19 缺失或 p.L858R EGFR 突变，将接受额外的化疗（4 个周期顺铂/培美曲塞或卡铂/培美曲塞）。随后，奥希替尼将作为标准治疗继续使用，直到疾病进展或无法耐受毒性。主要终点是 PFS。次要终点包括总生存期、缓解率、安全性和生活质量。同时进行转化研究，以确定疾病进展或 ctDNA 持续存在时 ctDNA 中突变进化的模式。招募于 2021 年 12 月开始。
PACE-LUNG 试验旨在评估针对高早期治疗失败风险患者进行治疗升级的生物标志物驱动策略的疗效和安全性。这种方法不仅旨在改善治疗结果，还旨在限制高风险患者预期的额外毒性。
2019-004757-88（EudraCT）。
