Retrospective study of the combination of TP and PF regimens with or without immune checkpoint inhibitors for the first-line treatment of locally advanced or advanced esophageal squamous cell carcinoma

Abstract

Objective: To investigate the efficacy and safety differences between the cisplatin + paclitaxel (TP) and cisplatin + fluorouracil (PF) regimens in combination with or without immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC) first-line treatment and prognostic factors. Methods: We selected the medical records of patients with late stage ESCC admitted to the hospital between 2019 and 2021. Based on the first-line treatment regimen, control groups were divided into chemotherapy plus ICIs ( n = 243) and non-ICIs ( n = 171), 119 (49%) in the TP + ICIs group, 124 (51%) in the PF + ICIs group, 83 (48.5%) in the TP group, and 88 (51.5%) in the PF group in the control group. We analyzed and compared factors related to efficacy, safety, or response to toxicity and prognosis across four subgroups. Results: The overall objective response rate (ORR) and disease control rate (DCR) of the TP plus ICIs group were 42.1% (50/119) and 97.5% (116/119), respectively, which were 6.6% and 7.2% higher than those of the PF plus ICIs group. Patients in the TP combined with ICIs group had higher overall survival (OS) and progression-free survival (PFS) than those in the PF combined with ICIs group [hazard ratio (HR) = 1.702, 95% confidence interval (CI): 0.767–1.499, p = 0.0167 and HR = 1.158, 95% CI: 0.828–1.619, p = 0.0055] ORR and DCR were 15.7% (13/83) and 85.5% (71/83) in the TP chemotherapy alone group, significantly higher than the PF group [13.6% (12/88) and 72.2% (64/88)] ( p < 0.05), OS and PFS were also better in patients treated with TP regimen chemotherapy than PF (HR = 1.173, 95% CI: 0.748–1.839, p = 0.0014 and HR = 0.1.245, 95% CI: 0.711–2.183, p = 0.0061). Furthermore, following the combination of TP and PF diets with ICIs, the OS of the patients was higher than that of the group treated with chemotherapy alone (HR = 0.526, 95% CI: 0.348–0.796, p = 0.0023 and HR = 0.781, 95% CI: 0.0.491–1.244, p < 0.001). Regression analysis showed that the neutrophil-to-lymphocyte ratio (NLR), the control nuclear status score (CONUT), and the systematic immune inflammation index (SII) were independent prognostic factors for the efficacy of immunotherapy ( p < 0.05). The overall incidence of treatment-associated adverse events (TRAEs) was 79.4% (193/243) and 60.8% (104/171) in the experimental and control groups, respectively, and there was no statistically significant difference in TRAEs between TP + ICIs (80.6%) and PF + ICIs (78.2%) (61.4%) and PF groups (60.2%) ( p > 0.05). Overall, 21.0% (51/243) of patients in the experimental group experienced immune-related adverse events (irAEs), and all of these adverse effects were tolerated or remitted following drug treatment without affecting follow-up. Conclusion: The TP regimen was associated with better PFS and OS with or without ICIs. Furthermore, high CONUT scores, high NLR ratios, and high SII were found to be associated with poor prognosis in combination immunotherapy.

Prognostic value of controlling nutritional status on clinical and survival outcomes in cancer patients treated with immunotherapy

“…The salient features of the incorporated articles are succinctly outlined in Table 2 . Three of these investigations were conducted in Japan 23 , 28 , 29 , and five in China 24 , 26 , 27 , 30 , 31 . The range of NOS scores observed in the research encompassed values between 6 and 9, signifying that all included studies exhibited a high level of quality.…”

“…All seven studies included in the analysis were retrospective 23 , 24 , 26 , 28 – 31 , while one was single-arm study 27 . Two studies were conducted in patients diagnosed with ESCC patients 30 , 31 ; one study was in HCC patients 27 , one study was in esophageal cancer (EC) patients 26 , one study was in GC patients 24 , one study was in NSCLC patients 23 , one study was in squamous cell carcinoma of the head and neck (HNSCC) patients 28 , and one study was in RCC patients 29 . Furthermore, 7 studies reported CONUT’s role in prognosticating OS outcome 23 , 24 , 26 , 28 – 31 , all 8 studies provided the data of CONUT for PFS prognosis 23 , 24 , 26 – 31 , 3 studies provided the data of CONUT for DCR prognosis 23 , 26 , 28 , and 4 studies provided the data of CONUT for ORR prognosis 23 , 26 , 28 , 31 .…”

PD-1 inhibitor combined with chemotherapy for first-line treatment of esophageal squamous cell carcinoma patients with distant metastasis: a real-world retrospective study

“…The chemotherapy regimens used in clinical practice in different regions are also not unified. In China, the TP regimen is mainly used, while in other countries, the PF regimen is more popular ( 16 ). The results of this study showed that the median PFS of patients with PD-1 inhibitors combined with the TP regimen was more than one month longer than that of patients with the combined PF regimen, and there was statistical significance.…”

“…In a retrospective study on the first-line treatment of locally advanced or advanced ESCC with or without TP and PF combined with immune checkpoint inhibitors (ICIs), it was found that the ORR and DCR in the TP+ICIs group were 42.1% (50/119) and 97.5% (116/119), respectively, which were 6.6% and 7.2% higher than those in the PF+ICIs group. Regardless of whether the TP regimen is combined with ICI or not, the PFS and OS benefits of the TP regimen are significantly better than those of the PF regimen ( 16 ). Related studies have shown that in clinical trials, the ORR of patients receiving PD-1 inhibitors combined with TP or FP seems to vary, possibly due to different chemotherapy regimens that may cause different changes in the tumor microenvironment.…”

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

“… 6 Currently, the combination of chemotherapy and ICIs has become the standard first-line treatment for patients with ESCC and is widely used during clinical practices. 7 A series of Phase III clinical trials, such as KEYNOTE-590, 8 CheckMate 648, 9 ESCORT-1ST, 10 JUPITER-06, 11 ORIENT-15, 12 ASTRUM-007 13 and RATIONALE 306, 14 have demonstrated that the combination of anti-PD-1 antibody significantly improved progression-free survival (PFS) and overall survival (OS) as compared with chemotherapy alone in patients with advanced or metastatic ESCC. 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.…”