Table 5.
Current therapeutic indications of immune checkpoint inhibitors.
| Therapy | Mode of Action | Approval | Indications |
|---|---|---|---|
| Ipilimumab (Yervoy) | Inhibitor of CTLA-4 | Since 2011 | Melanoma (metastatic) |
| Nivolumab (Opdivo) | Inhibitor of PD-1 | Since 2014 | (1) surgically inoperative melanoma; |
| (2) relapsed colorectal cancer that is characterized by high microsatellite instability (MSI-hi), | |||
| (3) gastric cancer (The Pharmaceuticals and Medical Devices Agency (PMDA) of Japan), | |||
| (4) advanced liver cancer that has been previously treated with sorafenib; | |||
| Since 2018 | (5) mesothelioma (PMDA); | ||
| Since 2020 | (6) unresectable advanced or recurrent esophageal cancer that has progressed following chemotherapy (PMDA), | ||
| (7) unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma after previous fluoropyrimidine- and platinum-based chemotherapy. | |||
| Pembrolizumab (Keytruda) | Inhibitor of PD-1 | Since 2014 | (1) surgically inoperative melanoma; |
| Since 2017 | (2) advanced non-small cell lung cancer (NSCLC, first line), | ||
| (3) bladder cancer (first line), | |||
| (4) all metastatic solid tumor types classified as MSI-hi (high microsatellite instability) or dMMR (deficient DNA mismatch repair) (second line), | |||
| (5) advanced recurrent cancer of the stomach and gastroesophageal junction; | |||
| Since 2018 | (6) patients with cervical cancer expressing PD-L1 that is metastatic or has recurred after previous chemotherapy treatment, | ||
| (7) adult and pediatric patients with primary mediastinal large B-cell lymphoma (PMBCL) that is refractory or has relapsed after two or more prior systemic treatments, | |||
| (8) advanced, treatment-resistant hepatocellular carcinoma, the most common type of liver cancer; | |||
| Since 2019 | (9) stage III non-small cell lung cancer (NSCLC) that is PD-L1-positive and is not amenable to surgery or chemo-radiation treatment (first-line), | ||
| (10) advanced esophageal squamous cell cancer, | |||
| (11) advanced endometrial carcinoma in patients with disease progression following prior systemic therapy but are ineligible for surgery or radiation, | |||
| Since 2020 | (12) advanced endometrial carcinoma in patients with disease progression following prior systemic therapy but are ineligible for surgery or radiation, | ||
| (13) unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (first line), | |||
| (14) recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation, | |||
| (15) unresectable or metastatic tumor mutational burden-high solid tumors, which have progressed and have no satisfactory alternative treatment options. | |||
| Durvalumab (Imfinzi) | anti-PD-L1 inhibitor | Since 2014 | (1) advanced bladder cancer, |
| Since 2018 | (2) unresectable, stage III non-small cell lung cancer (NSCLC) that hasn’t progressed after prior chemo-radiation treatment; | ||
| Since 2020 | (3) extensive-stage small cell lung cancer (ES-SCLC) in combination with standard-of-care chemotherapy (as a first line). | ||
| Avelumab (Bavencio) | a PD-L1 inhibitor | Since 2014 | (1) advanced bladder cancer, |
| Since 2017 | (2) for the treatment of Merkel cell carcinoma (EMA), | ||
| Since 2020 | (3) for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-based chemotherapy. | ||
| Atezolizumab (Tecentriq) | anti-PD-L1 inhibitor | Since 2014 | (1) metastatic, chemotherapy-resistant NSCLC, |
| Since 2019 | (2) unresectable (inoperable) or metastatic triple-negative breast cancer that also expresses PD-L1, (in combination with chemotherapy, as a first line). | ||
| (3) small cell lung cancer-ES-SCLC, (in combination with chemotherapy, as a first line). | |||
| (4) metastatic non-small cell lung cancer-nonsquamous NSCLC without EGFR or ALK molecular aberrations, (in combination with chemotherapy, as a first line). | |||
| Since 2020 | (5) BRAF V600 mutation-positive advanced melanoma (in combination with cobimetinib and vemurafenib). | ||
| Cemiplimab (Libtayo) | anti-PD-1 inhibitor | Since 2018 | cutaneous squamous cell carcinoma, metastatic or locally advanced |
| Nivolumab | inhibitor of PD-1 | Since 2018 | (1) melanoma (PMDA), |
| plus | (2) advanced renal cell carcinoma, the most common form of kidney cancer (FDA, EMA) | ||
| ipilimumab | inhibitor of CTLA-4 | (3) relapsed or refractory colorectal cancer characterized by high microsatellite instability (MSI-hi) or deficient DNA mismatch repair (dMMR) (FDA). | |
| Since 2020 | (4) advanced hepatocellular carcinoma, the most common form of liver cancer, in patients who have previously been treated with sorafenib.(FDA) | ||
| (5) metastatic non-small cell lung cancer (NSCLC) that expresses PD-L1 and does not possess mutations in the EGFR or ALK genes. A triple combination comprising nivolumab, ipilimumab and platinum-doublet chemotherapy was approved (FDA) as a first-line therapy for the same indication including recurrent NSCLC. | |||
| Atezolizumab | anti-PD-L1 inhibitor | Since 2020 | previously untreated hepatocellular carcinoma. |
| plus | |||
| bevacizumab | anti-VEGF Ab |