Background:The combined use of anti-programmed cell death protein1(PD-1)/anti-cytotoxic T-lymphocyte associated protein 4(CTLA-4)check-point inhibitors has been effective in various cancer types.The SouthwestOncology ...Background:The combined use of anti-programmed cell death protein1(PD-1)/anti-cytotoxic T-lymphocyte associated protein 4(CTLA-4)check-point inhibitors has been effective in various cancer types.The SouthwestOncology Group(SWOG)Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors(DART)S1609 study investigated ipilimumab and nivolumab in ultra-rare cancers,including small cell carcinoma of the ovary,hypercalcemic type(SCCOHT).The purpose of the study wasto evaluate the potential clinical benefitof ipilimumab and nivolumab in patients with SCCOHT.Methods:DART was a prospective,open-labeled,multicenter(>1,000 US sites),multi-cohort phase II clinical trial of intravenous administration of ipilimumab(1 mg/kg,every 6 weeks)plus nivolumab(240 mg,every 2 weeks).The pri-mary endpoint was overall response rate[ORR,confirmed complete response(CR)and partial response(PR)]per RECIST.Secondary endpoints includedprogression-free survival(PFS),overall survival(OS),clinical benefit rate(CBR;overall response plus stable disease≥6 months),and toxicity.Immune responseswere also evaluated.Results:Six patients(median age,30.5 years;median,2 prior therapies;nopriorimmunotherapy exposure)with advanced/metastatic SCCOHT were evalu-able.ORR and CBR were both 16.7%(1/6)with one patient having a confirmedCR lasting 46.2+months.However,another patient had a confirmed immuneCR(iCR)with immune PFS(iPFS)of 53+months[ORR/iORR,33.3%(2/6)].Notably,the latter patient had a progressing lesion at 24 weeks after initialresponse,but with renewed regression with ongoing therapy,suggesting delayedpseudo-progression.At 12-months,3 patients remained alive.Median PFS was1.4 months(range,0.9 months-not reached);median OS was 14.2 months(2months-not reached).No adverse events caused treatment discontinuation.Conclusion:Two of 6 patients(33.3%)with SCCOHT achieved durable CR/iCRand long-term survival with ipilimumab plus nivolumab.Correlative studies todetermine response and resistance markers are ongoing.展开更多
基金National Institutes of HealthNational Cancer Institute,Grant/Award Numbers:U10CA180888,U10CA180819,UG1CA233320,UG1CA233193,UG1CA233198,UG1CA233340Bristol Myers Squibb Company。
文摘Background:The combined use of anti-programmed cell death protein1(PD-1)/anti-cytotoxic T-lymphocyte associated protein 4(CTLA-4)check-point inhibitors has been effective in various cancer types.The SouthwestOncology Group(SWOG)Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors(DART)S1609 study investigated ipilimumab and nivolumab in ultra-rare cancers,including small cell carcinoma of the ovary,hypercalcemic type(SCCOHT).The purpose of the study wasto evaluate the potential clinical benefitof ipilimumab and nivolumab in patients with SCCOHT.Methods:DART was a prospective,open-labeled,multicenter(>1,000 US sites),multi-cohort phase II clinical trial of intravenous administration of ipilimumab(1 mg/kg,every 6 weeks)plus nivolumab(240 mg,every 2 weeks).The pri-mary endpoint was overall response rate[ORR,confirmed complete response(CR)and partial response(PR)]per RECIST.Secondary endpoints includedprogression-free survival(PFS),overall survival(OS),clinical benefit rate(CBR;overall response plus stable disease≥6 months),and toxicity.Immune responseswere also evaluated.Results:Six patients(median age,30.5 years;median,2 prior therapies;nopriorimmunotherapy exposure)with advanced/metastatic SCCOHT were evalu-able.ORR and CBR were both 16.7%(1/6)with one patient having a confirmedCR lasting 46.2+months.However,another patient had a confirmed immuneCR(iCR)with immune PFS(iPFS)of 53+months[ORR/iORR,33.3%(2/6)].Notably,the latter patient had a progressing lesion at 24 weeks after initialresponse,but with renewed regression with ongoing therapy,suggesting delayedpseudo-progression.At 12-months,3 patients remained alive.Median PFS was1.4 months(range,0.9 months-not reached);median OS was 14.2 months(2months-not reached).No adverse events caused treatment discontinuation.Conclusion:Two of 6 patients(33.3%)with SCCOHT achieved durable CR/iCRand long-term survival with ipilimumab plus nivolumab.Correlative studies todetermine response and resistance markers are ongoing.
