Abstract：
BACKGROUND: The optimal subsequent treatment strategy for locally advanced non-small cell lung cancer (LA-NSCLC) after chemoradiotherapy (CRT) and consolidative durvalumab therapy remains unknown. We aimed to determine the optimal subsequent treatment strategy for this clinical population.
METHODS: We retrospectively enrolled 523 consecutive patients with LA-NSCLC treated with CRT and analyzed the treatment outcomes of subsequent therapy after progression following CRT and consolidative durvalumab therapy. Patients who received tyrosine kinase inhibitors as subsequent therapy were excluded.
RESULTS: Out of 122 patients who received subsequent chemotherapy, 55% underwent platinum-based, 25% non-platinum-based, and 20% immune checkpoint inhibitor (ICI)-containing therapies. In the platinum-based group, patients with a durvalumab-progression-free survival (Dur-PFS) ≥ 1 year had a significantly longer median subsequent therapy-PFS (SubTx-PFS) than those with Dur-PFS < 1 year (13.2 months vs. 4.7 months; hazard ratio, 0.45; 95% confidence interval, 0.21-0.97; P = .04). Furthermore, among patients receiving non-platinum-based chemotherapy, the median SubTx-PFS was longer in the combined with angiogenesis inhibitor group than in the without group, although the difference was not statistically significant. No significant difference of SubTx-PFS was observed between the reason for durvalumab discontinuation and the outcomes of ICI-containing therapy.
CONCLUSIONS: In clinical practice, platinum-based chemotherapy rechallenge is frequently employed following progression subsequent to CRT and consolidative durvalumab therapy for LA-NSCLC. Optimal treatment strategies may consider Dur-PFS and angiogenesis inhibitor feasibility. Further research is warranted to identify clinical biomarkers that can help identify patients who would benefit from ICI rechallenge.
METHODS: We retrospectively enrolled 523 consecutive patients with LA-NSCLC treated with CRT and analyzed the treatment outcomes of subsequent therapy after progression following CRT and consolidative durvalumab therapy. Patients who received tyrosine kinase inhibitors as subsequent therapy were excluded.
RESULTS: Out of 122 patients who received subsequent chemotherapy, 55% underwent platinum-based, 25% non-platinum-based, and 20% immune checkpoint inhibitor (ICI)-containing therapies. In the platinum-based group, patients with a durvalumab-progression-free survival (Dur-PFS) ≥ 1 year had a significantly longer median subsequent therapy-PFS (SubTx-PFS) than those with Dur-PFS < 1 year (13.2 months vs. 4.7 months; hazard ratio, 0.45; 95% confidence interval, 0.21-0.97; P = .04). Furthermore, among patients receiving non-platinum-based chemotherapy, the median SubTx-PFS was longer in the combined with angiogenesis inhibitor group than in the without group, although the difference was not statistically significant. No significant difference of SubTx-PFS was observed between the reason for durvalumab discontinuation and the outcomes of ICI-containing therapy.
CONCLUSIONS: In clinical practice, platinum-based chemotherapy rechallenge is frequently employed following progression subsequent to CRT and consolidative durvalumab therapy for LA-NSCLC. Optimal treatment strategies may consider Dur-PFS and angiogenesis inhibitor feasibility. Further research is warranted to identify clinical biomarkers that can help identify patients who would benefit from ICI rechallenge.
摘要：
背景：局部晚期非小细胞肺癌（LA-NSCLC）在放化疗（CRT）和合并durvalumab治疗后的最佳后续治疗策略仍然未知。我们旨在确定该临床人群的最佳后续治疗策略。
方法：我们回顾性招募了523例接受CRT治疗的LA-NSCLC患者，并分析了CRT和Durvalumab合并治疗后进展后后续治疗的治疗结果。接受酪氨酸激酶抑制剂作为后续治疗的患者被排除在外。
结果：在接受后续化疗的122例患者中，55%采用铂金制，25%非铂金基,和含20％免疫检查点抑制剂（ICI）的疗法。在铂族中，Durvalumab无进展生存期（Dur-PFS）≥1年的患者的中位后续治疗PFS（SubTx-PFS）明显长于Dur-PFS<1年的患者（13.2个月与4.7个月；危险比，0.45；95%置信区间，0.21-0.97；P=.04）。此外，在接受非铂类化疗的患者中，合并血管生成抑制剂组的中位SubTx-PFS长于无血管生成抑制剂组,尽管差异无统计学意义。在Durvalumab停药的原因和含ICI治疗的结果之间没有观察到SubTx-PFS的显着差异。
结论：在临床实践中，在接受CRT和Durvalumab巩固治疗LA-NSCLC后进展后,经常采用铂类化疗再激发.最佳治疗策略可考虑Dur-PFS和血管生成抑制剂的可行性。进一步的研究是必要的，以确定临床生物标志物，可以帮助识别患者谁将受益于ICI再挑战。
方法：我们回顾性招募了523例接受CRT治疗的LA-NSCLC患者，并分析了CRT和Durvalumab合并治疗后进展后后续治疗的治疗结果。接受酪氨酸激酶抑制剂作为后续治疗的患者被排除在外。
结果：在接受后续化疗的122例患者中，55%采用铂金制，25%非铂金基,和含20％免疫检查点抑制剂（ICI）的疗法。在铂族中，Durvalumab无进展生存期（Dur-PFS）≥1年的患者的中位后续治疗PFS（SubTx-PFS）明显长于Dur-PFS<1年的患者（13.2个月与4.7个月；危险比，0.45；95%置信区间，0.21-0.97；P=.04）。此外，在接受非铂类化疗的患者中，合并血管生成抑制剂组的中位SubTx-PFS长于无血管生成抑制剂组,尽管差异无统计学意义。在Durvalumab停药的原因和含ICI治疗的结果之间没有观察到SubTx-PFS的显着差异。
结论：在临床实践中，在接受CRT和Durvalumab巩固治疗LA-NSCLC后进展后,经常采用铂类化疗再激发.最佳治疗策略可考虑Dur-PFS和血管生成抑制剂的可行性。进一步的研究是必要的，以确定临床生物标志物，可以帮助识别患者谁将受益于ICI再挑战。
