Cancer reports (Hoboken, N.J.) · 2026
First-Line PD-1 Inhibitor-Based Therapy for Advanced or Metastatic Esophageal Squamous Cell Carcinoma: A Revised Systematic Review and Meta-Analysis of Phase III Trials.
СтатьяСистематический обзорМетаанализНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Rothweiler Vincent, Roderburg Christoph, Koeksal Muemtaz, Jensen Björn Erik Ole, Feldt Torsten, Gencer Ilyas, Fischer Johannes C, Budach Wilfried, Knoefel Wolfram Trudo, Lu Guangyu, Bölke Edwin
Аннотация
BACKGROUND AND PURPOSE: Immune checkpoint blockade has changed the first-line treatment landscape for advanced esophageal squamous cell carcinoma (ESCC), but the magnitude and consistency of benefit across phase III trials require careful synthesis.
METHODS: We conducted a PRISMA 2020-guided systematic review of PubMed, Embase, CENTRAL, and Web of Science (January 1, 2015 to April 30, 2025) for phase III randomized trials comparing first-line PD-1 inhibitor-based therapy with chemotherapy in advanced/metastatic ESCC. The primary endpoint was overall survival (OS). Secondary endpoints were safety and prespecified subgroup outcomes. RoB 2 was used for risk-of-bias assessment; certainty of evidence was judged with GRADE. A fixed-effect inverse-variance model was prespecified for the primary common-effect analysis, with random-effects and sensitivity analyses performed secondarily.
RESULTS: Six eligible phase III trials were included in the primary analysis (KEYNOTE-590 ESCC subgroup, CheckMate-648 nivolumab-plus-chemotherapy arm, ESCORT-1st, JUPITER-06, ORIENT-15, and RATIONALE-306). Across the six parent-trial reports, 4137 patients were randomized overall; for pooling, KEYNOTE-590 was restricted to the prespecified ESCC subgroup and CheckMate-648 to the nivolumab-plus-chemotherapy comparison. PD-1 inhibitor-based therapy significantly improved OS versus chemotherapy alone (pooled HR 0.68, 95% CI: 0.63-0.74; I2 = 0%, interpreted as low statistical heterogeneity with caution because only six studies were pooled). Qualitative assessment indicated that the treatment effect was generally larger in PD-L1-high populations; however, biomarker-defined subgroup data were not sufficiently harmonized for formal pooling, and the magnitude of benefit in very low or PD-L1-negative disease remains uncertain. Grade ≥ 3 treatment-related adverse events were common in both arms, whereas immune-related toxicities were more frequent with PD-1 inhibitor-based therapy and required active monitoring.
CONCLUSION: First-line PD-1 inhibitor-based therapy confers a robust OS benefit in advanced/metastatic ESCC and supports chemoimmunotherapy as a contemporary standard of care. Remaining uncertainties relate mainly to biomarker-negative disease, assay heterogeneity, and cross-trial differences in chemotherapy backbone and geographic composition.
METHODS: We conducted a PRISMA 2020-guided systematic review of PubMed, Embase, CENTRAL, and Web of Science (January 1, 2015 to April 30, 2025) for phase III randomized trials comparing first-line PD-1 inhibitor-based therapy with chemotherapy in advanced/metastatic ESCC. The primary endpoint was overall survival (OS). Secondary endpoints were safety and prespecified subgroup outcomes. RoB 2 was used for risk-of-bias assessment; certainty of evidence was judged with GRADE. A fixed-effect inverse-variance model was prespecified for the primary common-effect analysis, with random-effects and sensitivity analyses performed secondarily.
RESULTS: Six eligible phase III trials were included in the primary analysis (KEYNOTE-590 ESCC subgroup, CheckMate-648 nivolumab-plus-chemotherapy arm, ESCORT-1st, JUPITER-06, ORIENT-15, and RATIONALE-306). Across the six parent-trial reports, 4137 patients were randomized overall; for pooling, KEYNOTE-590 was restricted to the prespecified ESCC subgroup and CheckMate-648 to the nivolumab-plus-chemotherapy comparison. PD-1 inhibitor-based therapy significantly improved OS versus chemotherapy alone (pooled HR 0.68, 95% CI: 0.63-0.74; I2 = 0%, interpreted as low statistical heterogeneity with caution because only six studies were pooled). Qualitative assessment indicated that the treatment effect was generally larger in PD-L1-high populations; however, biomarker-defined subgroup data were not sufficiently harmonized for formal pooling, and the magnitude of benefit in very low or PD-L1-negative disease remains uncertain. Grade ≥ 3 treatment-related adverse events were common in both arms, whereas immune-related toxicities were more frequent with PD-1 inhibitor-based therapy and required active monitoring.
CONCLUSION: First-line PD-1 inhibitor-based therapy confers a robust OS benefit in advanced/metastatic ESCC and supports chemoimmunotherapy as a contemporary standard of care. Remaining uncertainties relate mainly to biomarker-negative disease, assay heterogeneity, and cross-trial differences in chemotherapy backbone and geographic composition.