The Efficacy Of Chemotherapy And Immunotherapy For Patients With Advanced Gastric Cancer And Colorectal Cancer And The Analyses Of Prognostic Factors

Part ?:Efficacy and safety of biweekly triplet chemotherapy with paclitaxel liposome,oxaliplatin and S-1/5-fluorouracil as first-line treatment for advanced gastric cancer leucopenia(75.6%),nausea/vomiting(56.1%),anemia(48.8%)and impaired liver function(29.3%).Grade 3-4 hematological toxicities included neutropenia(58.5%),leucopenia(24.4%)and thrombocytopenia(4.9%).Grade 3 non-hematological toxicities included nausea/vomiting(4.9%),diarrhea(2.4%)and impaired liver function(2.4%).There was no grade 4 non-hematological toxicity.No treatment-related death was observed.Background:Chemotherapy is currently the main treatment modality for advanced gastric cancer.Previous first-line triplet chemotherapy for advanced gastric cancer had severe toxicity,so more reasonable dose regimens need to be explored.Reports of paclitaxel liposome-based triplets for the first-line treatment of gastric cancer are limited to tri-weekly regimens.Compared with tri-weekly regimens,biweekly regimens have the potential advantages of reducing toxicity and improving completion rate of chemotherapy,but evidence for its application is still lacking.This study aims to evaluate the efficacy and safety of biweekly paclitaxel liposome combined with oxaliplatin and S-1/5-fluorouracil(5-Fu)as first-line chemotherapy in advanced gastric cancer.Methods:Clinical data of 41 patients with advanced measurable gastric cancer who received biweekly paclitaxel liposome combined with oxaliplatin and S-1/5-Fu regimen was retrospectively collected.The following regimen was administered:paclitaxel liposome was given by intravenous drop for 3h(135?150mg/m2)on day 1;oxaliplatin was given by intravenous drop for 2h(80?95mg/m2)on day 2;S-1 was given orally twice daily(40?60mg depending on patient's body surface area)after breakfast and dinner,for 10 consecutive days followed by a 4-day rest;alternatively,leucovorin was given by intravenous drop(200 mg/m2)followed by 5-Fu 2000 mg/m2 continuous infusion for 44 hours.This schedule was repeated every 14 days.The efficacy and safety of this regimen was analyzed.Results:All 41 patients achieved evaluable efficacy,among which 3 achieved complete response(CR),23 achieved partial response(PR)and 11 achieved stable disease(SD)with objective response rate(ORR)of 63.4%and disease control rate(DCR)of 90.2%.The median progression-free survival time(PFS)and overall survival time(OS)were 8.5 months and 18.8 months,respectively.The most common toxicities were neutropenia(78.0%),Conclusions:The regimen of biweekly paclitaxel liposome combined with oxaliplatin and S-1/5-Fu is effective and tolerable as first-line treatment in advanced gastric cancer.Part ?:Efficacy and safety of HX008,an anti-PD1 antibody,combined with irinotecan as second-line treatment for patients with advanced gastric or gastroesophageal junction cancerBackground:The combination of anti-programmed death-1(PD-1)antibody with chemotherapy as second-line treatment for advanced gastric or gastroesophageal junction(G/GEJ)cancer has not been prospectively reported.The role of PD-1 antibody plus irinotecan,in this setting and population is unclear.Methods:This multicenter,open-label,single-arm,phase ? trial was conducted in 11 Chinese hospitals.Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to,or intolerant of,first-line chemotherapy with a platinum and/or fluoropyrimidine based regimen.Patients received HX008 200mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity.The primary end point was objective response rate(ORR)as assessed according to RECIST V.1.1.Results:Between October 2018 and September 2019,a total of 58 patients with advanced G/GEJ cancer were enrolled in this study.Median follow-up was 10.5 months(range 7.4-18.9).Confirmed ORR was observed in 16 patients,for an ORR of 27.6%(95%CI 16.1%to 39.1%);19 patients experienced stable disease,leading to a disease control rate of 60.3%(95%CI 46.4%to 73.0%).ORR in patients with PD-ligand 1(PD-L1)positive(Combined Positive Score(CPS)?1)and negative(CPS<1)tumors was 38.5%(5/13)and 37.5%(3/8),respectively.Median duration of response was 8.0 months(range 1.5-12.5),6 of 16(37.5%)responses were ongoing.Median progression-free survival(PFS)was 4.2 months(95%CI 2.2 to 5.5).Median overall survival(OS)was not reached(NR)(95%CI 8.7 to NR).The most common treatment-related adverse events of grade 3 or 4 included neutropenia(32.8%),leukopenia(31.0%),anemia(17.2%),decreased appetite(8.6%),vomit(6.9%),nausea(6.9%)and fatigue(5.2%).There were no treatment-related deaths.Conclusions:The combination of anti-PD-1 antibody HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer,which warrants phase ? randomized controlled trial.Part ?:The clinicopathological characteristics and outcomes of patients with colorectal cancer metastatic to the ovaryBackground:Ovarian metastases are uncommon in women with colorectal cancer and harbor poor prognosis.The optimal therapeutic strategies have not been established for ovarian metastasis from colorectal cancer,and there are limited reports in the literature.This study aims to explore the clinicopathological characteristics,treatment strategies and prognosis of patients with ovarian metastases from colorectal cancer.Methods:A total of 122 consecutive female patients with ovarian metastases from colorectal cancer who were treated at a single institute between 2010 and 2015 were identified.Clinicopathologic features,treatment details and survival data of these patients were retrospectively analyzed,and the correlations between cliniopathologic features and prognosis were analyzed.Results:The median overall survival(OS)was 19.7 months.The 1-year,3-year and 5-year OS rates were 72.1%,24.7%and 9.9%,respectively.A total of 99(81.1%)patients underwent oophorectomy.The median OS was significantly longer in patients who underwent oophorectomy than in patients who did not undergo oophorectomy(21.9 months vs.10.3 months,p<0.001).Patients who underwent complete resection had a prolonged median OS than those who underwent palliative debulking surgery(38.2 months vs.18.7 months,p<0.001).Thirty-six patients received systemic chemotherapy as the initial treatment and could be evaluated,and the ORR was 22.2%.The ORR to chemotherapy for ovarian metastases and extraovarian sites in 26 patients was 11.5%and 34.6%,separately.In the univariate analyses,ovary as the only site of metastasis(p=0.005),primary tumor resection(p<0.001),and oophorectomy(p<0.001)were associated with improved survival.Multivariate analysis showed that primary tumor resection(HR=0.348,p<0.001)and oophorectomy(HR=0.483,p=0.005)were independent prognostic factors for OS.Conclusions:Ovarian metastases are relatively insensitive to chemotherapy.Patients with ovarian metastases from colorectal cancer might derive a survival benefit from surgical resection of the primary tumor and ovaries.