Clinical efficacy of combination therapy of an immune checkpoint inhibitor with taxane plus platinum versus an immune checkpoint inhibitor with fluorouracil plus platinum in the first-line treatment of patients with locally advanced, metastatic, or recurrent esophageal squamous cell carcinoma

Abstract

BackgroundChemotherapy combined with immune checkpoints inhibitors (ICIs) has been established as a standard treatment for locally advanced, metastatic, or recurrent esophageal squamous cell cancer (ESCC). However, the optimal chemotherapy regimen in combination therapy is still unclear.PurposeTo investigate the efficacy and adverse events of the fluorouracil plus platinum (FP) and taxane plus platinum (TP) regimens in ESCC patients receiving chemo-immunotherapy, we conducted this systematic review and meta-analysis.MethodsPotentially eligible studies were searched from Medline, Embase, Web of Science, and the Cochrane Library. Pooled rates of overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events were compared between ICIs+TP and ICIs+FP groups in ESCC patients receiving first-line chemo-immunotherapy.ResultsA total of 10 clinical trials were included, of which 5 were randomized controlled trials. Compared with chemotherapy alone, chemo-immunotherapy significantly improved the OS of ESCC patients (pooled HR=0.69; 95% CI, 0.63–0.76; p<0.01). Pooled analysis revealed that ESCC patients receiving ICIs+TP had significantly higher ORR, DCR, PFS, and OS rates than those receiving ICIs+FP. No statistically significant difference in the pooled incidence rate of treatment-related death was found (2.3% vs 0.9%, P=0.08). ICIs+TP had significantly higher rates of hematologic toxicity but lower rates of gastrointestinal toxicity than ICIs+FP.ConclusionsBased on the current data, the first-line treatment using ICIs+TP may be a better option than ICIs+FP in advanced, metastatic, or recurrent ESCC.

Clinical Efficacy of Taxol Plus Platinum (TP) Chemotherapy Combined with Delayed Administration of PD-1 Inhibitors in Patients with Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma: A Retrospective Study

“…In this study, a total of 22 patients developed grade 3–4 toxicity, including leukopenia, anemia, neutropenia, thrombocytopenia, nausea-vomiting and fatigue. In comparison to previous reports, 16 our study exhibited a reduction in grade 3/4 neutropenia (8.8%) and lymphopenia (5.9%). Because chemotherapy was initially designed with a principle of administering doses at the highest level of toleration, such high level of dose might induce immune cell toxicity.…”

“… 25 Phase III randomized controlled trials (KEYNOTE-590, 8 CheckMate-648, 9 ESCORT-1ST, 10 JUPITER-06, 11 ORIENT-15, 12 ASTRUM-007 13 and RATIONALE 306 14 ) have clinically confirmed synergistic treatment efficacy of chemotherapy combined with ICIs, and the standard of care for locally advanced, recurrent or metastatic ESCC has been built up. Since TP+ICIs has demonstrated superior treatment efficacy compared to PF+ICIs, 7 , 16 , 26 the current study focused on a retrospective analysis specifically investigating the therapeutic efficacy of combining TP with ICIs as a first-line treatment for patients diagnosed with locally advanced, recurrent, or metastatic ESCC. In addition, we went a step further by refining the sequence of chemotherapy and anti-PD-1 antibody administration based on insights from prior researches.…”

“… 15 Furthermore, several studies have indicated that platinum in combination with taxol (TP) + ICIs may offer advantages over platinum in combination with fluorouracil (PF) + ICIs for advanced or metastatic ESCC. 7 , 16 …”

Does nivolumab combined with fluorouracil-based chemotherapy produce higher objective response rate than other immunochemotherapy regimes in metastatic esophageal cancer?

“…Since immune checkpoint inhibitors (ICIs) combined with either fluorouracil + cisplatin (fluorouracil-based chemotherapy, FbCT) and paclitaxel + cisplatin (fluorouracil-free chemotherapy, FfCT) have become the standard first-line treatment for metastatic esophageal squamous cell carcinoma (ESCC), 2 , 3 , 4 , 5 , 6 this is a topical article exploring the optimal drug combination in cases where randomized controlled trials (RCTs) directly comparing various drugs, including cytotoxic and immunotherapeutic drugs, for metastatic ESCC patients, are lacking. In contrast to other meta-analysis, 7 this review by Gao et al. reports that Nivolumab + FbCT shows a significant advantage in objective response rate (ORR) compared to three other immunochemotherapy regimes (nivolumab + FbCT vs. camrelizumab + FbCT, OR 4.04; nivolumab + FbCT vs. camrelizumab + FfCT), OR 2.83; nivolumab + FbCT vs. toripalimab + FfCT, OR 2.47).…”

Advancements in the research of immune checkpoint inhibitors for the treatment of advanced esophageal squamous cell carcinoma

“…ICIs combined with TP demonstrate higher rates of hematological toxicity but lower rates of gastrointestinal toxicity compared to ICIs combined with FP. Therefore, for patients with advanced ESCC, first-line treatment with ICIs combined with TP may result in better clinical outcomes [74,75]. In second-line chemotherapy, PD-1 inhibitors have shown significant improvements in overall survival (OS) and objective response rate (ORR) for patients with advanced ESCC, particularly in those who are PD-L1 positive.…”