eTable 1. List of 29 solid tumor types or subtypes

eTable 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 type

eFigure 2. Forest plot of response rates among studies with anti-CTLA-4 monotherapy by tumor type

eFigure 3. Forest plot of response rates among studies with anti-PD-1/PD-L1 plus anti-CLTA-4 therapy by tumor type

eFigure 4. Forest plot of toxicity rates among studies with anti-PD-1/PD-L1 monotherapy by tumor type

eFigure 5. Forest plot of toxicity rates among studies with anti-CTLA-4 monotherapy by tumor type

eFigure 6. Forest plot of toxicity rates among studies with anti-PD-1/PD-L1 plus anti-CLTA-4 therapy by tumor type

eFigure 7. Forest plot of hazard ratios for overall survival among studies with anti-PD-1/PD-L1 monotherapy

eTable 1. List of 29 solid tumor types or subtypes

Adrenocortical Carcinoma Esophagogastric Carcinoma Ocular/Uveal Melanoma

Anal Cancer Germ Cell Tumor Other MSIBiliary Tract Cancer Glioblastoma Ovarian CancerBladder Cancer Head and Neck Pancreatic Cancer

Breast Carcinoma Hepatocellular Carcinoma Prostate Cancer

Cervical Cancer Melanoma Renal Cell Carcinoma

Colorectal Cancer – MSI Merkel Cell Carcinoma Sarcoma

Colorectal Cancer – MSS Mesothelioma Small Cell Lung Cancer

Cutaneous Squamous Cell Carcinoma Nasopharyngeal ThymicEndometrial Cancer Non-Small Cell Lung Cancer

eTable 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 Author Journal Year Drug General Tumor TypeLe Tourneau Annals of Oncology 2017 Avelumab Adrenocortical CarcinomaMorris Lancet Oncology 2017 Nivolumab Anal Cancer

Ioka Journal of Clinical Oncology 2019 Durvalumab Biliary Tract CancerKim Annals of Oncology 2018 Nivolumab Biliary Tract Cancer

Ueno Annals of Oncology 2018 Pembrolizumab Biliary Tract CancerRosenberg Lancet 2016 Atezolizumab Bladder Cancer

Apolo Journal of Clinical Oncology 2017 Avelumab Bladder CancerPowles JAMA Oncology 2017 Durvalumab Bladder Cancer

Sharma Lancet Oncology 2017 Nivolumab Bladder CancerBellmunt The New England Journal of

Medicine2017 Pembrolizumab Bladder Cancer

Schmid Cancer Research 2017 Atezolizumab Breast Carcinoma

Dirix Breast Cancer Research and Treatment

2018 Avelumab Breast Carcinoma

Rischin Annals of Oncology 2018 Cemiplimab Cervical CancerSantin Journal of Clinical Oncology 2018 Nivolumab Cervical Cancer

Chung Journal of Clinical Oncology 2018 Pembrolizumab Cervical CancerOverman Journal of Clinical Oncology 2018 Nivolumab Colorectal Cancer – MSI

Le Annals of Oncology 2018 Pembrolizumab Colorectal Cancer – MSIEng Lancet 2019 Atezolizumab Colorectal Cancer – MSS

Brahmer Journal of Clinical Oncology 2010 Nivolumab Colorectal Cancer – MSSLe The New England Journal of

Medicine2015 Pembrolizumab Colorectal Cancer – MSS

Migden The New England Journal of Medicine

2018 Cemiplimab Cutaneous Squamous Cell Carcinoma

Maubec Journal of Clinical Oncology 2018 Pembrolizumab Cutaneous Squamous Cell Carcinoma

Fleming Journal of Clinical Oncology 2017 Atezolizumab Endometrial Cancer

Chung Journal of Clinical Oncology 2016 Avelumab Esophagogastric CarcinomaKang Lancet 2017 Nivolumab Esophagogastric Carcinoma

Fuchs JAMA Oncology 2018 Pembrolizumab Esophagogastric CarcinomaAdra Journal of Clinical Oncology 2017 Pembrolizumab Germ Cell Tumor

Reardon Journal of Clinical Oncology 2017 Durvalumab GlioblastomaReardon Neuro-Oncology 2017 Nivolumab Glioblastoma

Ferris The New England Journal of Medicine

2016 Nivolumab Head and Neck

Bauml Journal of Clinical Oncology 2017 Pembrolizumab Head and NeckWainberg Journal of Clinical Oncology 2017 Durvalumab Hepatocellular Carcinoma

El-Khoueiry Lancet 2017 Nivolumab Hepatocellular CarcinomaZhu Lancet Oncology 2018 Pembrolizumab Hepatocellular Carcinoma

Wolchok The New England Journal of Medicine

2017 Nivolumab Melanoma

Robert The New England Journal of Medicine

2015 Pembrolizumab Melanoma

Kaufman Cancer Research 2017 Avelumab Merkel Cell CarcinomaTopalian Cancer Research 2017 Nivolumab Merkel Cell Carcinoma

Nghiem The New England Journal of Medicine

2016 Pembrolizumab Merkel Cell Carcinoma

Hassan Journal of Clinical Oncology 2017 Avelumab MesotheliomaScherpereel Journal of Clinical Oncology 2017 Nivolumab Mesothelioma

Kindler Journal of Clinical Oncology 2017 Pembrolizumab MesotheliomaMa Journal of Clinical Oncology 2018 Nivolumab Nasopharyngeal

Rittmeyer Lancet 2017 Atezolizumab Non-Small Cell Lung CancerGulley Lancet Oncology 2017 Avelumab Non-Small Cell Lung Cancer

Borghaei The New England Journal of Medicine

2015 Nivolumab Non-Small Cell Lung Cancer

Garon The New England Journal of Medicine

2015 Pembrolizumab Non-Small Cell Lung Cancer

Rittmeyer Lancet 2017 Atezolizumab Non-Small Cell Lung CancerGulley Lancet Oncology 2017 Avelumab Non-Small Cell Lung Cancer

Brahmer The New England Journal of Medicine

2015 Nivolumab Non-Small Cell Lung Cancer

Garon The New England Journal of Medicine

2015 Pembrolizumab Non-Small Cell Lung Cancer

Azad Journal for ImmunoTherapy of Cancer

2017 Nivolumab Other MSI

Diaz Annals of Oncology 2017 Pembrolizumab Other MSIDisis Journal of Clinical Oncology 2017 Avelumab Ovarian Cancer

Brahmer The New England Journal of Medicine

2012 BMS-936559 Ovarian Cancer

Hamanishi Journal of Clinical Oncology 2015 Nivolumab Ovarian CancerMatulonis Annals of Oncology 2019 Pembrolizumab Ovarian Cancer

Brahmer The New England Journal of Medicine

2012 BMS-936559 Pancreatic Cancer

O’Reilly Journal of Clinical Oncology 2018 Durvalumab Pancreatic CancerKim Journal of Clinical Oncology 2018 Atezolizumab Prostate Cancer

Fakhrejahani Journal of Clinical Oncology 2017 Avelumab Prostate CancerTopalian The New England Journal of

Medicine2012 Nivolumab Prostate Cancer

De Bono Journal of Clinical Oncology 2018 Pembrolizumab Prostate Cancer

McDermott Journal of Clinical Oncology 2016 Atezolizumab Renal Cell CarcinomaMotzer The New England Journal of

Medicine2015 Nivolumab Renal Cell Carcinoma

McDermott Journal of Clinical Oncology 2018 Pembrolizumab Renal Cell Carcinoma

D’Angelo Lancet Oncology 2018 Nivolumab SarcomaTawbi Lancet Oncology 2017 Pembrolizumab Sarcoma

Sequist Annals of Oncology 2016 Atezolizumab Small Cell Lung CancerReck Annals of Oncology 2018 Nivolumab Small Cell Lung Cancer

Chung Journal of Clinical Oncology 2018 Pembrolizumab Small Cell Lung CancerSeto Journal of Thoracic Oncology 2018 Nivolumab Thymic

Giaccone Journal of Clinical Oncology 2017 Pembrolizumab Thymic

Algazi Cancer 2016 anti-PD-1/anti-PD-L1

Ocular/Uveal melanoma

Namikawa Annals of Oncology 2017 Nivolumab Ocular/Uveal melanoma

List of studies with anti-CTLA-4 monotherapyFirst Author Journal Year Drug General Tumor TypeLheureux Journal of Clinical Oncology 2017 Ipilimumab Cervical Cancer

Chung Journal of Clinical Oncology 2010 Tremelimumab Colorectal Cancer – MSSBang Clinical Cancer Research 2017 Ipilimumab Esophagogastric Carcinoma

Ralph Clinical Cancer Research 2010 Tremelimumab Esophagogastric CarcinomaSangro Journal of Hepatology 2013 Tremelimumab Hepatocellular Carcinoma

Wolchok The New England Journal of Medicine

2017 Ipilimumab Melanoma

Ribas Journal of Clinical Oncology 2013 Tremelimumab MelanomaMaio Lancet Oncology 2017 Tremelimumab Mesothelioma

Zatloukal Journal of Clinical Oncology 2016 Tremelimumab Non-Small Cell Lung CancerJoshua Melanoma Research 2015 Tremelimumab Ocular/Uveal melanoma

Le Journal of Immunotherapy 2014 Ipilimumab Pancreatic CancerSharma Journal of Clinical Oncology 2018 Tremelimumab Pancreatic Cancer

Slovin Annals of Oncology 2013 Ipilimumab Prostate CancerYang Journal of Immunotherapy 2007 Ipilimumab Renal Cell Carcinoma

List of studies with anti-PD-1/PD-L1 plus anti-CTLA-4 therapyFirst Author Journal Year Drug General Tumor TypeIoka Journal of Clinical Oncology 2019 Durva/Treme Biliary Tract CancerBalar Cancer Research 2018 Durva/Treme Bladder Cancer

Rosenberg Annals of Oncology 2018 Ipi/Nivo Bladder CancerSanta-Maria Journal of Clinical Oncology 2017 Durva/Treme Breast Carcinoma

Callahan Journal of Clinical Oncology 2017 Durva/Treme Cervical CancerOverman Journal of Clinical Oncology 2018 Ipi/Nivo Colorectal Cancer – MSI

Chen Journal of Clinical Oncology 2019 Durva/Treme Colorectal Cancer – MSSJanjigian Journal of Clinical Oncology 2018 Ipi/Nivo Esophagogastric Carcinoma

Omuro Neuro Oncology 2018 Ipi/Nivo GlioblastomaKelley Journal of Clinical Oncology 2017 Durva/Treme Hepatocellular Carcinoma

Wolchok The New England Journal of Medicine

2017 Ipi/Nivo Melanoma

Long Lancet Oncology 2017 Ipi/Pembro MelanomaCalabro Lancet Respiratory Medicine 2018 Durva/Treme Mesothelioma

Disselhorst Lancet Respiratory Medicine 2019 Ipi/Nivo MesotheliomaAntonia Lancet Oncology 2016 Durva/Treme Non-Small Cell Lung Cancer

Hellmann Lancet Oncology 2017 Ipi/Nivo Non-Small Cell Lung CancerGubens Journal of Clinical Oncology 2017 Ipi/Pembro Non-Small Cell Lung Cancer

Piulats Rodriguez

Annals of Oncology 2018 Ipi/Nivo Ocular/Uveal melanoma

Callahan Journal of Clinical Oncology 2017 Durva/Treme Ovarian CancerBurger International Journal of

Gynecologic Cancer Society2018 Ipi/Nivo Ovarian Cancer

O’Reilly Journal of Clinical Oncology 2018 Durva/Treme Pancreatic Cancer

Sharma Journal of Clinical Oncology 2019 Ipi/Nivo Prostate CancerCallahan Journal of Clinical Oncology 2017 Durva/Treme Renal Cell Carcinoma

Motzer The New England Journal of Medicine

2018 Ipi/Nivo Renal Cell Carcinoma

Atkins Journal of Clinical Oncology 2017 Ipi/Pembro Renal Cell CarcinomaD’Angelo Lancet Oncology 2018 Ipi/Nivo Sarcoma

Cho Journal of Clinical Oncology 2018 Durva/Treme Small Cell Lung CancerHellmann Journal of Clinical Oncology 2017 Ipi/Nivo Small Cell Lung Cancer

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)

Response Rate Toxicity Rate

General Tumor Type TMB (median) Single Dual Difference Single Dual Difference

Ocular/Uveal melanoma 1.3000 0.0399 0.1200 0.0801 0.1250 0.5400 0.4150Pancreatic Cancer 1.8000 0.0485 0.0312 -0.0172 0.0606 0.2188 0.1581Mesothelioma 1.8000 0.1400 0.2692 0.1291 0.0833 0.2552 0.1719Colorectal Cancer – MSS 2.0000 0.0142 0.0084 -0.0058 0.2518 0.6356 0.3838Sarcoma 2.2134 0.0831 0.1579 0.0748 0.1905 0.1429 -0.0476Biliary Tract Cancer 2.5000 0.0656 0.1077 0.0420 0.1589 0.2308 0.0719Renal Cell Carcinoma 2.7000 0.2446 0.2765 0.0319 0.1851 0.3597 0.1746Prostate Cancer 2.7000 0.0475 0.1698 0.1223 0.1297 0.4906 0.3608Glioblastoma 2.7000 0.0844 0.0667 -0.0178 0.1660 0.5000 0.3340Ovarian Cancer 2.9672 0.0839 0.1941 0.1102 0.1823 0.4344 0.2521Hepatocellular Carcinoma 3.6000 0.1683 0.2000 0.0317 0.2128 0.2000 -0.0128Breast Carcinoma 3.6360 0.0595 0.1667 0.1072 0.1250 0.2778 0.1528Cervical Cancer 4.7368 0.0907 0.0357 -0.0550 0.1515 0.1250 -0.0265

Esophagogastric Carcinoma 5.0000 0.1084 0.1584 0.0500 0.1254 0.3663 0.2409

Non-Small Cell Lung Cancer 6.9139 0.1631 0.2813 0.1182 0.1083 0.3456 0.2373

Bladder Cancer 7.2535 0.1797 0.2643 0.0846 0.1276 0.3168 0.1892Small Cell Lung Cancer 9.9000 0.1388 0.1932 0.0544 0.1365 0.3902 0.2538Melanoma 14.4000 0.3862 0.5911 0.2050 0.1637 0.5216 0.3579Colorectal Cancer – MSI 45.0000 0.3283 0.5462 0.2179 0.1535 0.3193 0.1658

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)

General Tumor Type TMB(median)

Statistics Anti-PD-1/PD-L1 Monotherapy

Anti-CTLA-4 Monotherapy

Anti-PD-1/PD-L1 plus anti-CTLA-4

TherapyOcular/Uveal melanoma 1.30 Num. of Studies 2 1 1

Mean (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)

Mesothelioma 1.80 Num. of Studies 3 1 2

Mean (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 Cancer 1.80 Num. of Studies 1 2 1

Mean (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 – MSS

2.00 Num. of Studies 2 - 1

Mean (SD) 6.05 (1.48) - 6.60 ( NA)

Median (Range) 6.05 (5.00, 7.10) - 6.60 (6.60, 6.60)

Sarcoma 2.21 Num. of Studies 2 - 1

Mean (SD) 29.85 (27.08) - 14.30 ( NA)

Median (Range) 29.85 (10.70, 49.00) - 14.30 (14.30, 14.30)

Biliary Tract Cancer 2.50 Num. of Studies 3 - 1

Mean (SD) 10.47 (3.28) - 10.10 ( NA)

Median (Range) 9.10 (8.10, 14.22) - 10.10 (10.10, 10.10)

Thymic 2.50 Num. of Studies - - -

Mean (SD) - - -

Median (Range) - - -

Adrenocortical Carcinoma

2.70 Num. of Studies 1 - -

Mean (SD) 10.60 ( NA) - -

Median (Range) 10.60 (10.60, 10.60) - -

Germ Cell Tumor 2.70 Num. of Studies - - -

Mean (SD) - - -

Median (Range) - - -

Glioblastoma 2.70 Num. of Studies 1 - 1

Mean (SD) 9.80 ( NA) - 9.20 ( NA)

Median (Range) 9.80 (9.80, 9.80) - 9.20 (9.20, 9.20)

Prostate Cancer 2.70 Num. of Studies - - -

Mean (SD) - - -

Median (Range) - - -

Renal Cell Carcinoma 2.70 Num. of Studies 1 - -

Mean (SD) 25.00 ( NA) - -

Median (Range) 25.00 (25.00, 25.00) - -

Ovarian Cancer 2.97 Num. of Studies 2 - -

Mean (SD) 15.40 (6.51) - -

Median (Range) 15.40 (10.80, 20.00) - -

Hepatocellular Carcinoma

3.60 Num. of Studies 3 1 -

Mean (SD) 13.10 (0.17) 8.20 ( NA) -

Median (Range) 13.20 (12.90, 13.20) 8.20 (8.20, 8.20) -

Nasopharyngeal 3.60 Num. of Studies 1 - -

Mean (SD) 17.10 ( NA) - -

Median (Range) 17.10 (17.10, 17.10) - -

Breast Carcinoma 3.64 Num. of Studies - - -

Mean (SD) - - -

Median (Range) - - -

Endometrial Cancer 3.92 Num. of Studies 1 - -

Mean (SD) 9.60 ( NA) - -

Median (Range) 9.60 (9.60, 9.60) - -

Merkel Cell Carcinoma 4.30 Num. of Studies 1 - -

Mean (SD) 12.90 ( NA) - -

Median (Range) 12.90 (12.90, 12.90) - -

Cervical Cancer 4.74 Num. of Studies 1 - -

Mean (SD) 9.40 ( NA) - -

Median (Range) 9.40 (9.40, 9.40) - -

Esophagogastric Carcinoma

5.00 Num. of Studies 2 2 1

Mean (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 Neck 5.00 Num. of Studies 2 - -

Mean (SD) 7.75 (0.35) - -

Median (Range) 7.75 (7.50, 8.00) - -

Anal Cancer 5.40 Num. of Studies 1 - -

Mean (SD) 11.50 ( NA) - -

Median (Range) 11.50 (11.50, 11.50) - -

Non-Small Cell Lung Cancer

6.91 Num. of Studies 5 - 1

Mean (SD) 11.42 (2.91) - 10.90 ( NA)

Median (Range) 12.00 (8.40, 15.60) - 10.90 (10.90, 10.90)

Bladder Cancer 7.25 Num. of Studies 5 - 2

Mean (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 Cancer 9.90 Num. of Studies 2 - 2

Mean (SD) 8.30 (1.13) - 7.90 (0.00)

Median (Range) 8.30 (7.50, 9.10) - 7.90 (7.90, 7.90)

Melanoma 14.40 Num. of Studies 1 2 -

Mean (SD) 37.60 ( NA) 16.25 (5.16) -

Median (Range) 37.60 (37.60, 37.60) 16.25 (12.60, 19.90) -

Other MSI 30.00 Num. of Studies - - -

Mean (SD) - - -

Median (Range) - - -

Colorectal Cancer – MSI 45.00 Num. of Studies 1 - -

Mean (SD) 31.40 ( NA) - -

Median (Range) 31.40 (31.40, 31.40) - -

Cutaneous Squamous Cell Carcinoma

45.20 Num. of Studies - - -

Mean (SD) - - -

Median (Range) - - -

eFigure 1. Forest plot of response rates among studies with anti-PD-1/PD-L1 monotherapy by tumor type

eFigure 2. Forest plot of response rates among studies with anti-CTLA-4 monotherapy by tumor type

eFigure 3. Forest plot of response rates among studies with anti-PD-1/PD-L1 plus anti-CLTA-4 therapy by tumor type

eFigure 4. Forest plot of toxicity rates among studies with anti-PD-1/PD-L1 monotherapy by tumor type

eFigure 5. Forest plot of toxicity rates among studies with anti-CTLA-4 monotherapy by tumor type

eFigure 6. Forest plot of toxicity rates among studies with anti-PD-1/PD-L1 plus anti-CLTA-4 therapy by tumor type

eFigure 7. Forest plot of hazard ratios for overall survival among studies with anti-PD-1/PD-L1 monotherapy