![]() However, recent studies on chemotherapy modulating the immune TME have observations related to this speculation. So far we have no direct evidence to support this speculation in ESCC. Indeed, the effects of chemotherapeutic drugs on TME and immune cells are not fully understood, which may affect immunotherapy efficacy. Growing evidence suggest that the efficacy of ICB treatment is related to tumor microenvironment (TME). Moreover, a retrospective comparison of CF/PC BBC plus ICB using propensity-score matched cohorts based on real-world data may be a feasible alternative to provide important reference. RATIONALE-306 trial is being conducted globally with different BBC regimens, and the results will provide essential clinical data for future work. ![]() Because population characteristics differ between these trials, further investigations comparing chemoimmunotherapy-combination regimens are needed. However, this subgroup analysis from ORIENT-15 and the above observation lead to an interesting speculation that different BBC regimens combined with ICB may have different effects. Of note, the HR of ICB + CF subgroup was not statistically significant, which may be due to the small number of patients (7% of total). For the current studies, only ORIENT-15 study 1 was designed with stratification of chemotherapy regimens and results showed that HR for OS of ICB + PC vs. Similarly, for progression-free survival, ICB + PC seemed to have relatively more combination benefit compared with ICB + CF. However, in chemoimmunotherapy group, ICB + PC appeared to have a better reduction in overall mortality risk (HR ≤ 0.70, median OS ≥ 15 months). The median OS in chemotherapy group were all around 10–12 months regardless of CF or PC regimen. As for PC-based BBC studies (ORIENT-15, JUPITER-6, and ESCORT-1st have similar dose intensity of PC-chemotherapy), the median OS of chemotherapy group ranged from 11 to 12.5 months and that of chemoimmunotherapy group was increased at least to 15 months, with a more than 30% reduction risk of overall death (HR: 0.58–0.70).īecause of the differences in study design, a reasonable comparison of these studies is difficult but we can obtain some important information. ![]() The hazard ratio (HR) for chemoimmunotherapy relative to chemotherapy alone is around 0.72–0.74. 1)? For CF-based BBC studies (KEYNOTE-590 and CheckMate-648 have similar dose intensity of CF chemotherapy), the median OS of chemotherapy group was about 10 months (9.8–10.7), and that of chemoimmunotherapy was about 13 months. ![]() If we consider the BBC regimens for ICB, are there any differences among these trials (Fig. The KEYNOTE-590 and CheckMate-648 trials adopted CF regimen, while the ESCORT-1st, JUPITER-6 and ORIENT-15 mainly adopted PC regimen. 2 Of note, BBC regimens differed in each of the above-mentioned published trials in advanced ESCC. The efficacy and median overall survival (OS) appear generally comparable across the regimens in ESCC. For advanced ESCC, first-line chemotherapy regimens include paclitaxel plus cisplatin (PC), which is a common backbone chemotherapy (BBC) used in China, and 5-fluorouracil plus cisplatin (CF), which is a common BBC used in Western countries and Japan. ![]()
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