Analysis of the efficacy and safety of preoperative programmed death protein-1 inhibitor combined with chemotherapy in immunotherapy-sensitive patients with locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction
Objective To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1(PD-1)inhibitor with either oxaliplatin+capecitabine(CapeOx)or oxaliplatin+tegafur gimeracil oteracil potassium(SOX)in the treatment of locally advanced immunotherapy-sensitive gastric cancer(LAGC)or adenocarcinoma of the esophagogastric junction(AEG).Methods The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy-sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center,Unit Ⅲ,Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024.Patients with any one of the following three characteristics were immunotherapy-sensitive:(i)PD-L1 combined positive score(CPS)≥5;(ii)microsatellite instability-high(MSI-H)/mismatch repair deficiency(dMMR);or(iii)Epstein-Barr virus-encoded RNA(EBER)positivity.All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery.Patients with immune system diseases,distant metastases,or human epidermal growth factor receptor 2 positivity were excluded.Factors analyzed included pathological complete response,clinical complete response,major pathological response,R0 resection rate,surgical conversion rate,and safety of the treatment,including immune-related adverse events(irAEs)and surgical complications.Results The study cohort comprised 39 patients(28 men and 11 women)of median age 62(range 44-79)years.After the above-described preoperative treatment,radical resection of the 14 tumors that were initially considered unresectable was achieved(surgical conversion rate:14/14).Twenty-three of the remaining 25 patients underwent radical resection.The last two patients achieved clinical complete responses and opted for a"non-surgical strategy"(watch and wait).Overall,37 patients(94.9％)underwent radical resection,with an R0 resection rate of 100％(37/37),pathological complete response rate of 48.6％(18/37),and major pathological response rate of 62.2％(23/37).Of the 24 patients with CPS ≥ 5(non-MSI-H/dMMR and non-EBER positive),11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response.Of the eight patients with MSI-H/dMMR,six achieved pathological complete responses and one a clinical complete response.Of the seven patients with EBER positivity,one achieved a pathological complete response.After excluding patients with major pathological complete responses,there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients(7.769±5.570 vs.15.538±16.870,t=2.287,P=0.041).All patients tolerated preoperative immunotherapy well;nine patients(9/39,23.1％)had Grade Ⅰ-Ⅱ irAEs.There were no Grade Ⅲ-Ⅳ irAEs.The five patients with pyloric obstruction before treatment tolerated normal diets after treatment.The incidence of postoperative complications among all patients who underwent surgery was 18.9％(7/37),including one case of Grade ⅢA anastomotic leakage,one of Grade ⅢA intestinal obstruction,one of Grade Ⅱ abdominal hemorrhage,two of Grade Ⅱ abdominal infection,one of Grade Ⅰ intestinal obstruction.Additionally,one patient developed COVID-19 postoperatively.All patients recovered with symptomatic treatment.Conclusion We found that preoperative treatment of patients with LAGC or AEG of one of three types(CPS≥5,dMMR+MSI-H,and EBER positivity)with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety,with high surgical conversion,R0 resection,and complete response rates.
Stomach neoplasms,locally advancedAdenocarcinoma of esophagogastric junctionProgrammed death protein-1 inhibitorNeoadjuvant therapyConversion therapyPathological complete response rateClinical complete reponse rate
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