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eTable 1. List of 29 solid tumor types or subtypeseTable 2. List of studies with anti-PD-1/PD-L1 monotherapy, anti-CTLA-4 monotherapy, and anti-PD-1/PD-L1 plus anti-CTLA-4 therapy eTable 3. Pooled response and toxicity rates for each tumor type within each treatment category (single: anti-PD-1/PD-L1; dual: anti-PD-1/PD-L1 plus anti-CTLA-4)eTable 4. Descriptive statistics of median overall survival for each tumor type within each treatment category (single: anti-PD-1/PD-L1, anti-CTLA-4; dual: anti-PD-1/PD-L1 plus anti-CTLA-4) eFigure 1. Forest plot of response rates among studies with anti-PD-1/PD-L1 monotherapy by tumor typeeFigure 2. Forest plot of response rates among studies with anti-CTLA-4 monotherapy by tumor typeeFigure 3. Forest plot of response rates among studies with anti-PD-1/PD-L1 plus anti-CLTA-4 therapy by tumor typeeFigure 4. Forest plot of toxicity rates among studies with anti-PD-1/PD-L1 monotherapy by tumor typeeFigure 5. Forest plot of toxicity rates among studies with anti-CTLA-4 monotherapy by tumor typeeFigure 6. Forest plot of toxicity rates among studies with anti-PD-1/PD-L1 plus anti-CLTA-4 therapy by tumor typeeFigure 7. Forest plot of hazard ratios for overall survival among studies with anti-PD-1/PD-L1 monotherapyeTable 1. List of 29 solid tumor types or subtypesAdrenocortical CarcinomaEsophagogastric CarcinomaOcular/Uveal MelanomaAnal CancerGerm Cell TumorOther MSIBiliary Tract CancerGlioblastomaOvarian CancerBladder CancerHead and NeckPancreatic CancerBreast CarcinomaHepatocellular CarcinomaProstate CancerCervical CancerMelanomaRenal Cell CarcinomaColorectal Cancer – MSIMerkel Cell CarcinomaSarcomaColorectal Cancer – MSSMesotheliomaSmall Cell Lung CancerCutaneous Squamous Cell CarcinomaNasopharyngealThymicEndometrial CancerNon-Small Cell Lung CancereTable 2. List of studies with anti-PD-1/PD-L1 monotherapy, anti-CTLA-4 monotherapy, and anti-PD-1/PD-L1 plus anti-CTLA-4 therapy List of studies with anti-PD-1/PD-L1 monotherapyFirst AuthorJournalYearDrugGeneral Tumor TypeLe TourneauAnnals of Oncology2017AvelumabAdrenocortical CarcinomaMorrisLancet Oncology2017NivolumabAnal CancerIokaJournal of Clinical Oncology2019DurvalumabBiliary Tract CancerKimAnnals of Oncology2018NivolumabBiliary Tract CancerUenoAnnals of Oncology2018PembrolizumabBiliary Tract CancerRosenbergLancet2016AtezolizumabBladder CancerApoloJournal of Clinical Oncology2017AvelumabBladder CancerPowlesJAMA Oncology2017DurvalumabBladder CancerSharmaLancet Oncology2017NivolumabBladder CancerBellmuntThe New England Journal of Medicine2017PembrolizumabBladder CancerSchmidCancer Research2017AtezolizumabBreast CarcinomaDirixBreast Cancer Research and Treatment2018AvelumabBreast CarcinomaRischinAnnals of Oncology2018CemiplimabCervical CancerSantinJournal of Clinical Oncology2018NivolumabCervical CancerChungJournal of Clinical Oncology2018PembrolizumabCervical CancerOvermanJournal of Clinical Oncology2018NivolumabColorectal Cancer – MSILeAnnals of Oncology2018PembrolizumabColorectal Cancer – MSIEngLancet2019AtezolizumabColorectal Cancer – MSSBrahmerJournal of Clinical Oncology2010NivolumabColorectal Cancer – MSSLeThe New England Journal of Medicine2015PembrolizumabColorectal Cancer – MSSMigdenThe New England Journal of Medicine2018CemiplimabCutaneous Squamous Cell CarcinomaMaubecJournal of Clinical Oncology2018PembrolizumabCutaneous Squamous Cell CarcinomaFlemingJournal of Clinical Oncology2017AtezolizumabEndometrial CancerChungJournal of Clinical Oncology2016AvelumabEsophagogastric CarcinomaKangLancet2017NivolumabEsophagogastric CarcinomaFuchsJAMA Oncology2018PembrolizumabEsophagogastric CarcinomaAdraJournal of Clinical Oncology2017PembrolizumabGerm Cell TumorReardonJournal of Clinical Oncology2017DurvalumabGlioblastomaReardonNeuro-Oncology2017NivolumabGlioblastomaFerrisThe New England Journal of Medicine2016NivolumabHead and NeckBaumlJournal of Clinical Oncology2017PembrolizumabHead and NeckWainbergJournal of Clinical Oncology2017DurvalumabHepatocellular CarcinomaEl-KhoueiryLancet2017NivolumabHepatocellular CarcinomaZhuLancet Oncology2018PembrolizumabHepatocellular CarcinomaWolchokThe New England Journal of Medicine2017NivolumabMelanomaRobertThe New England Journal of Medicine2015PembrolizumabMelanomaKaufmanCancer Research2017AvelumabMerkel Cell CarcinomaTopalianCancer Research2017NivolumabMerkel Cell CarcinomaNghiemThe New England Journal of Medicine2016PembrolizumabMerkel Cell CarcinomaHassanJournal of Clinical Oncology2017AvelumabMesotheliomaScherpereelJournal of Clinical Oncology2017NivolumabMesotheliomaKindlerJournal of Clinical Oncology2017PembrolizumabMesotheliomaMaJournal of Clinical Oncology2018NivolumabNasopharyngealRittmeyerLancet2017AtezolizumabNon-Small Cell Lung CancerGulleyLancet Oncology2017AvelumabNon-Small Cell Lung CancerBorghaeiThe New England Journal of Medicine2015NivolumabNon-Small Cell Lung CancerGaronThe New England Journal of Medicine2015PembrolizumabNon-Small Cell Lung CancerRittmeyerLancet2017AtezolizumabNon-Small Cell Lung CancerGulleyLancet Oncology2017AvelumabNon-Small Cell Lung CancerBrahmerThe New England Journal of Medicine2015NivolumabNon-Small Cell Lung CancerGaronThe New England Journal of Medicine2015PembrolizumabNon-Small Cell Lung CancerAzadJournal for ImmunoTherapy of Cancer2017NivolumabOther MSIDiazAnnals of Oncology2017PembrolizumabOther MSIDisisJournal of Clinical Oncology2017AvelumabOvarian CancerBrahmerThe New England Journal of Medicine2012BMS-936559Ovarian CancerHamanishiJournal of Clinical Oncology2015NivolumabOvarian CancerMatulonisAnnals of Oncology2019PembrolizumabOvarian CancerBrahmerThe New England Journal of Medicine2012BMS-936559Pancreatic CancerO’ReillyJournal of Clinical Oncology2018DurvalumabPancreatic CancerKimJournal of Clinical Oncology2018AtezolizumabProstate CancerFakhrejahaniJournal of Clinical Oncology2017AvelumabProstate CancerTopalianThe New England Journal of Medicine2012NivolumabProstate CancerDe BonoJournal of Clinical Oncology2018PembrolizumabProstate CancerMcDermottJournal of Clinical Oncology2016AtezolizumabRenal Cell CarcinomaMotzerThe New England Journal of Medicine2015NivolumabRenal Cell CarcinomaMcDermottJournal of Clinical Oncology2018PembrolizumabRenal Cell CarcinomaD’AngeloLancet Oncology2018NivolumabSarcomaTawbiLancet Oncology2017PembrolizumabSarcomaSequistAnnals of Oncology2016AtezolizumabSmall Cell Lung CancerReckAnnals of Oncology2018NivolumabSmall Cell Lung CancerChungJournal of Clinical Oncology2018PembrolizumabSmall Cell Lung CancerSetoJournal of Thoracic Oncology2018NivolumabThymicGiacconeJournal of Clinical Oncology2017PembrolizumabThymicAlgaziCancer2016anti-PD-1/anti-PD-L1Ocular/Uveal melanomaNamikawaAnnals of Oncology2017NivolumabOcular/Uveal melanomaList of studies with anti-CTLA-4 monotherapyFirst AuthorJournalYearDrugGeneral Tumor TypeLheureuxJournal of Clinical Oncology2017IpilimumabCervical CancerChungJournal of Clinical Oncology2010TremelimumabColorectal Cancer – MSSBangClinical Cancer Research2017IpilimumabEsophagogastric CarcinomaRalphClinical Cancer Research2010TremelimumabEsophagogastric CarcinomaSangroJournal of Hepatology2013TremelimumabHepatocellular CarcinomaWolchokThe New England Journal of Medicine2017IpilimumabMelanomaRibasJournal of Clinical Oncology2013TremelimumabMelanomaMaioLancet Oncology2017TremelimumabMesotheliomaZatloukalJournal of Clinical Oncology2016TremelimumabNon-Small Cell Lung CancerJoshuaMelanoma Research2015TremelimumabOcular/Uveal melanomaLeJournal of Immunotherapy2014IpilimumabPancreatic CancerSharmaJournal of Clinical Oncology2018TremelimumabPancreatic CancerSlovinAnnals of Oncology2013IpilimumabProstate CancerYangJournal of Immunotherapy2007IpilimumabRenal Cell CarcinomaList of studies with anti-PD-1/PD-L1 plus anti-CTLA-4 therapyFirst AuthorJournalYearDrugGeneral Tumor TypeIokaJournal of Clinical Oncology2019Durva/TremeBiliary Tract CancerBalarCancer Research2018Durva/TremeBladder CancerRosenbergAnnals of Oncology2018Ipi/NivoBladder CancerSanta-MariaJournal of Clinical Oncology2017Durva/TremeBreast CarcinomaCallahanJournal of Clinical Oncology2017Durva/TremeCervical CancerOvermanJournal of Clinical Oncology2018Ipi/NivoColorectal Cancer – MSIChenJournal of Clinical Oncology2019Durva/TremeColorectal Cancer – MSSJanjigianJournal of Clinical Oncology2018Ipi/NivoEsophagogastric CarcinomaOmuroNeuro Oncology2018Ipi/NivoGlioblastomaKelleyJournal of Clinical Oncology2017Durva/TremeHepatocellular CarcinomaWolchokThe New England Journal of Medicine2017Ipi/NivoMelanomaLongLancet Oncology2017Ipi/PembroMelanomaCalabroLancet Respiratory Medicine2018Durva/TremeMesotheliomaDisselhorstLancet Respiratory Medicine2019Ipi/NivoMesotheliomaAntoniaLancet Oncology2016Durva/TremeNon-Small Cell Lung CancerHellmannLancet Oncology2017Ipi/NivoNon-Small Cell Lung CancerGubensJournal of Clinical Oncology2017Ipi/PembroNon-Small Cell Lung CancerPiulats RodriguezAnnals of Oncology2018Ipi/NivoOcular/Uveal melanomaCallahanJournal of Clinical Oncology2017Durva/TremeOvarian CancerBurgerInternational Journal of Gynecologic Cancer Society2018Ipi/NivoOvarian CancerO’ReillyJournal of Clinical Oncology2018Durva/TremePancreatic CancerSharmaJournal of Clinical Oncology2019Ipi/NivoProstate CancerCallahanJournal of Clinical Oncology2017Durva/TremeRenal Cell CarcinomaMotzerThe New England Journal of Medicine2018Ipi/NivoRenal Cell CarcinomaAtkinsJournal of Clinical Oncology2017Ipi/PembroRenal Cell CarcinomaD’AngeloLancet Oncology2018Ipi/NivoSarcomaChoJournal of Clinical Oncology2018Durva/TremeSmall Cell Lung CancerHellmannJournal of Clinical Oncology2017Ipi/NivoSmall Cell Lung CancereTable 3. Pooled response and toxicity rates for each tumor type within each treatment category (single: anti-PD-1/PD-L1; dual: anti-PD-1/PD-L1 plus anti-CTLA-4)Response RateToxicity RateGeneral Tumor TypeTMB (median)SingleDualDifferenceSingleDualDifferenceOcular/Uveal melanoma1.30000.03990.12000.08010.12500.54000.4150Pancreatic Cancer1.80000.04850.0312-0.01720.06060.21880.1581Mesothelioma1.80000.14000.26920.12910.08330.25520.1719Colorectal Cancer – MSS2.00000.01420.0084-0.00580.25180.63560.3838Sarcoma2.21340.08310.15790.07480.19050.1429-0.0476Biliary Tract Cancer2.50000.06560.10770.04200.15890.23080.0719Renal Cell Carcinoma2.70000.24460.27650.03190.18510.35970.1746Prostate Cancer2.70000.04750.16980.12230.12970.49060.3608Glioblastoma2.70000.08440.0667-0.01780.16600.50000.3340Ovarian Cancer2.96720.08390.19410.11020.18230.43440.2521Hepatocellular Carcinoma3.60000.16830.20000.03170.21280.2000-0.0128Breast Carcinoma3.63600.05950.16670.10720.12500.27780.1528Cervical Cancer4.73680.09070.0357-0.05500.15150.1250-0.0265Esophagogastric Carcinoma5.00000.10840.15840.05000.12540.36630.2409Non-Small Cell Lung Cancer6.91390.16310.28130.11820.10830.34560.2373Bladder Cancer7.25350.17970.26430.08460.12760.31680.1892Small Cell Lung Cancer9.90000.13880.19320.05440.13650.39020.2538Melanoma14.40000.38620.59110.20500.16370.52160.3579Colorectal Cancer – MSI45.00000.32830.54620.21790.15350.31930.1658eTable 4. Descriptive statistics of median overall survival for each tumor type within each treatment category (single: anti-PD-1/PD-L1, anti-CTLA-4; dual: anti-PD-1/PD-L1 plus anti-CTLA-4) General Tumor TypeTMB(median)StatisticsAnti-PD-1/PD-L1 MonotherapyAnti-CTLA-4 MonotherapyAnti-PD-1/PD-L1 plus anti-CTLA-4 TherapyOcular/Uveal melanoma1.30Num. of Studies211Mean (SD)10.45 (4.03)12.80 ( NA)12.70 ( NA)Median (Range)10.45 (7.60, 13.30)12.80 (12.80, 12.80)12.70 (12.70, 12.70)Mesothelioma1.80Num. of Studies312Mean (SD)11.50 (0.69)10.70 ( NA)16.25 (0.49)Median (Range)11.90 (10.70, 11.90)10.70 (10.70, 10.70)16.25 (15.90, 16.60)Pancreatic Cancer1.80Num. of Studies121Mean (SD)3.60 ( NA)3.80 (0.28)3.10 ( NA)Median (Range)3.60 (3.60, 3.60)3.80 (3.60, 4.00)3.10 (3.10, 3.10)Colorectal Cancer – MSS2.00Num. of Studies2-1Mean (SD)6.05 (1.48)-6.60 ( NA)Median (Range)6.05 (5.00, 7.10)-6.60 (6.60, 6.60)Sarcoma2.21Num. of Studies2-1Mean (SD)29.85 (27.08)-14.30 ( NA)Median (Range)29.85 (10.70, 49.00)-14.30 (14.30, 14.30)Biliary Tract Cancer2.50Num. of Studies3-1Mean (SD)10.47 (3.28)-10.10 ( NA)Median (Range)9.10 (8.10, 14.22)-10.10 (10.10, 10.10)Thymic2.50Num. of Studies---Mean (SD)---Median (Range)---Adrenocortical Carcinoma2.70Num. of Studies1--Mean (SD)10.60 ( NA)--Median (Range)10.60 (10.60, 10.60)--Germ Cell Tumor2.70Num. of Studies---Mean (SD)---Median (Range)---Glioblastoma2.70Num. of Studies1-1Mean (SD)9.80 ( NA)-9.20 ( NA)Median (Range)9.80 (9.80, 9.80)-9.20 (9.20, 9.20)Prostate Cancer2.70Num. of Studies---Mean (SD)---Median (Range)---Renal Cell Carcinoma2.70Num. of Studies1--Mean (SD)25.00 ( NA)--Median (Range)25.00 (25.00, 25.00)--Ovarian Cancer2.97Num. of Studies2--Mean (SD)15.40 (6.51)--Median (Range)15.40 (10.80, 20.00)--Hepatocellular Carcinoma3.60Num. of Studies31-Mean (SD)13.10 (0.17)8.20 ( NA)-Median (Range)13.20 (12.90, 13.20)8.20 (8.20, 8.20)-Nasopharyngeal3.60Num. of Studies1--Mean (SD)17.10 ( NA)--Median (Range)17.10 (17.10, 17.10)--Breast Carcinoma3.64Num. of Studies---Mean (SD)---Median (Range)---Endometrial Cancer3.92Num. of Studies1--Mean (SD)9.60 ( NA)--Median (Range)9.60 (9.60, 9.60)--Merkel Cell Carcinoma4.30Num. of Studies1--Mean (SD)12.90 ( NA)--Median (Range)12.90 (12.90, 12.90)--Cervical Cancer4.74Num. of Studies1--Mean (SD)9.40 ( NA)--Median (Range)9.40 (9.40, 9.40)--Esophagogastric Carcinoma5.00Num. of Studies221Mean (SD)5.43 (0.24)8.77 (5.56)6.90 ( NA)Median (Range)5.43 (5.26, 5.60)8.77 (4.83, 12.70)6.90 (6.90, 6.90)Head and Neck5.00Num. of Studies2--Mean (SD)7.75 (0.35)--Median (Range)7.75 (7.50, 8.00)--Anal Cancer5.40Num. of Studies1--Mean (SD)11.50 ( NA)--Median (Range)11.50 (11.50, 11.50)--Non-Small Cell Lung Cancer6.91Num. of Studies5-1Mean (SD)11.42 (2.91)-10.90 ( NA)Median (Range)12.00 (8.40, 15.60)-10.90 (10.90, 10.90)Bladder Cancer7.25Num. of Studies5-2Mean (SD)11.77 (4.22)-12.40 (4.10)Median (Range)10.30 (7.90, 18.20)-12.40 (9.50, 15.30)Small Cell Lung Cancer9.90Num. of Studies2-2Mean (SD)8.30 (1.13)-7.90 (0.00)Median (Range)8.30 (7.50, 9.10)-7.90 (7.90, 7.90)Melanoma14.40Num. of Studies12-Mean (SD)37.60 ( NA)16.25 (5.16)-Median (Range)37.60 (37.60, 37.60)16.25 (12.60, 19.90)-Other MSI30.00Num. of Studies---Mean (SD)---Median (Range)---Colorectal Cancer – MSI45.00Num. of Studies1--Mean (SD)31.40 ( NA)--Median (Range)31.40 (31.40, 31.40)--Cutaneous Squamous Cell Carcinoma45.20Num. of Studies---Mean (SD)---Median (Range)---eFigure 1. Forest plot of response rates among studies with anti-PD-1/PD-L1 monotherapy by tumor typeeFigure 2. Forest plot of response rates among studies with anti-CTLA-4 monotherapy by tumor typeeFigure 3. Forest plot of response rates among studies with anti-PD-1/PD-L1 plus anti-CLTA-4 therapy by tumor typeeFigure 4. Forest plot of toxicity rates among studies with anti-PD-1/PD-L1 monotherapy by tumor typeeFigure 5. Forest plot of toxicity rates among studies with anti-CTLA-4 monotherapy by tumor typeeFigure 6. Forest plot of toxicity rates among studies with anti-PD-1/PD-L1 plus anti-CLTA-4 therapy by tumor typeeFigure 7. Forest plot of hazard ratios for overall survival among studies with anti-PD-1/PD-L1 monotherapy ................
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