List of EMA-approved immune checkpoint inhibitors with their approved indication
| ICIs | Author | Approved indication | Special consideration | Predictive biomarker | |
|---|---|---|---|---|---|
| Anti-PD-1 | Nivolumab | Larkin et al. [29] | Advanced melanoma | N/A | N/A |
| Weber et al. [30] | Resected melanoma with metastatic lymph nodes or resected metastases | Adjuvant setting | N/A | ||
| Forde et al. [31] | Resectable NSCLC with high recurrence risk | Neoadjuvant setting in combination with platinum-based chemotherapy | PD-L1 ≥ 1% | ||
| Borghaei et al. [32] | Locally advanced or metastatic NSCLC | Subsequent therapy after chemotherapy | N/A | ||
| Motzer et al. [33] | Advanced renal cell carcinoma | Subsequent treatment | N/A | ||
| Choueiri et al. [34] | Advanced renal cell carcinoma | First line therapy in combination with cabozantinib | N/A | ||
| Ferris et al. [35] | Recurrent or metastatic squamous head and neck cancer | Subsequent therapy after platinum-based chemotherapy | N/A | ||
| Bajorin et al. [36] | Resected urothelial carcinoma with high recurrence risk | Adjuvant setting | PD-L1 ≥ 1% | ||
| van der Heijden [37] | Locally advanced or metastatic urothelial carcinoma | First line therapy combined with cisplatin and gemcitabine | N/A | ||
| Sharma et al. [38] | Locally advanced or metastatic urothelial carcinoma | Subsequent therapy after platinum-based chemotherapy | N/A | ||
| Kelly et al. [39] | Esophageal or gastroesophageal junction carcinoma with residual pathologic disease after neoadjuvant chemoradiation | Adjuvant setting | N/A | ||
| Doki et al. [40] | Advanced unresectable, recurrent or metastatic squamous cell esophageal carcinoma | First line therapy combined with fluoropyrimidine and platinum-based chemotherapy | PD-L1 ≥ 1% | ||
| Kato et al. [41] | Advanced unresectable, recurrent or metastatic squamous cell esophageal carcinoma | Subsequent therapy after platinum and fluoropyrimidine-based chemotherapy | N/A | ||
| Janjigian et al. [42] | Advanced or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma | First line therapy combined with fluoropyrimidine and platinum-based chemotherapy | - HER2 negative- PD-L1 + with CPS ≥ 5 | ||
| Pembrolizumab | Luke et al. [43] | Completely resected melanoma stage IIB, IIC or III | Adjuvant setting | N/A | |
| Schachter et al. [44] | Irresectable or metastatic melanoma | N/A | N/A | ||
| Reck et al. [45] | Metastatic NSCLC | First line therapy | - PD-L1 + CPS ≥ 50- EGFR and ALK negative | ||
| Gandhi et al. [46] | Metastatic NSCLC and non-squamous cell carcinoma | First line therapy in combination with pemetrexed and platinum-based chemotherapy | EGFR and ALK negative | ||
| Paz-Ares et al. [47] | Squamous NSCLC | First line therapy in combination with paclitaxel and platinum-based chemotherapy | N/A | ||
| Herbst et al. [48] | Locally advanced or metastatic NSCLC | If EGFR or ALK positive, targeted therapy should be received prior to pembrolizumab | PD-L1 + CPS ≥ 1 | ||
| Bellmunt et al. [49] | Locally advanced or metastatic urothelial carcinoma | Subsequent therapy after prior platinum-based chemotherapy | N/A | ||
| Balar et al. [50] | Locally advanced or metastatic urothelial carcinoma | Unfit for platinum | PD-L1 + CPS ≥ 10 | ||
| Burtness et al. [51] | Recurrent or metastatic squamous head and neck cancer | First line therapy in combination with 5-fluorouracil + platinum | PD-L1 + CPS ≥ 1 | ||
| First line therapy, monotherapy | PD-L1 + CPS ≥ 50 | ||||
| Choueiri et al. [52] | Resected renal cell carcinoma (including resected metastases) | Adjuvant setting | N/A | ||
| Rini et al. [53] | Advanced renal cell carcinoma | First line therapy in combination with axitinib | N/A | ||
| Motzer et al. [54] | Advanced renal cell carcinoma | First line therapy in combination with lenvatinib | N/A | ||
| André et al. [55] | Metastatic colorectal cancer | First line therapy or after previous chemotherapy based on fluoropyrimidines | Deficient in mismatch repair (dMMR) | ||
| Marabelle et al. [56] | Recurrent or advanced endometrial carcinoma | Subsequent therapy in progression to platinum-based chemotherapy | dMMR | ||
| Metastatic gastric cancer | Subsequent therapy | ||||
| Metastatic small intestine cancer | |||||
| Metastatic biliary tract cancer | |||||
| Sun et al. [57] | Metastatic esophageal cancer or adenocarcinoma of gastroesophageal junction | First line therapy in combination with platinum and fluoropyrimidine-based chemotherapy | PD-L1 + CPS ≥ 10 | ||
| Schmid et al. [58] | Localized triple negative breast cancer | Perioperative setting | N/A | ||
| Cortes et al. [59] | Metastatic triple negative breast cancer | First line therapy in combination with chemotherapy | PD-L1 + CPS ≥ 10 | ||
| Makker et al. [60] | Advanced or recurrent endometrial carcinoma | Subsequent therapy after platinum-based chemotherapy | N/A | ||
| Monk et al. [61] | Recurrent or metastatic cervical cancer | In combination with or without bevacizumab | PD-L1 + CPS ≥ 1 | ||
| Janjigian et al. [62] | Unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma HER2 positive | First line therapy in combination with trastuzumab + platinum-based chemotherapy and fluoropyrimidines | - HER2 positive- PD-L1 + CPS ≥ 1 | ||
| Rha et al. [63] | Unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma | First line therapy in combination with platinum-based chemotherapy and fluoropyrimidines | - HER2 negative- PD-L1 + CPS ≥ 1 | ||
| Kelley et al. [64] | Unresectable or metastatic biliary tract cancer | First line therapy in combination with cisplatin and gemcitabine | N/A | ||
| Dostarlimab | Mirza et al. [65] | Advanced endometrial cancer (new diagnosed or relapse) | In combination with carboplatin and paclitaxel | dMMR | |
| Oaknin et al. [66] | Primary advanced or recurrent endometrial cancer (relapse or progression after first line therapy) | Monotherapy | dMMR | ||
| Cemiplimab | Migden et al. [67] | Metastatic or locally advanced squamous cell skin cancer | N/A | N/A | |
| Stratigos et al. [68] | Locally advanced or metastastic basal cell carcinoma | Subsequent therapy, in progression or those who not tolerate a Hedgehog pathway inhibitor | N/A | ||
| Sezer et al. [69] | Locally advanced NSCLC not candidates for chemoradiotherapy or metastatic NSCLC | First line therapy, monotherapy | - PD-L1 ≥ 50%- No EGFR, ALK or ROS1 mutations | ||
| Gogishvili et al. [70] | Locally advanced NSCLC not candidates for chemoradiotherapy or metastatic NSCLC | First line therapy, in combination with platinum-based chemotherapy | - PD-L1 ≥ 1%- No EGFR, ALK or ROS1 mutations | ||
| Tewari et al. [71] | Metastatic or recurrent cervical cancer | Subsequent therapy in progression to a platinum-based chemotherapy | N/A | ||
| Retifanlimab | Lakhani et al. [72] | Locally advanced or metastatic Merkel cell carcinoma | First line therapy | N/A | |
| Tislelizumab | Shen et al. [73] | Unresectable, locally advanced or metastatic esophageal squamous cell carcinoma | Subsequent therapy, after progression to platinum-based chemotherapy | N/A | |
| Anti-PD-L1 | Atezolizumab | Powles et al. [74] | Locally advanced or metastatic urothelial carcinoma | Subsequent therapy after platinum-based chemotherapy or first line for unfit for platinum | N/A |
| Rittmeyer et al. [75] | Locally advanced or metastatic NSCLC | After previous chemotherapy. If EGFR or ALK mutation, targeted therapy must have been received prior to atezolizumab | N/A | ||
| Avelumab | D’Angelo [76] | Metastatic Merkel cell carcinoma | N/A | N/A | |
| Powles et al. [77] | Locally advanced or metastatic urothelial carcinoma with no progression after platinum-based chemotherapy | First line therapy-maintenance therapy | N/A | ||
| Motzer et al. [78] | Advanced renal cell carcinoma | First line therapy combined with axitinib | N/A | ||
| Durvalumab | Antonia et al. [79] | Unresectable and locally advanced NSCLC with no progression after chemoradiotherapy | Maintenance therapy after chemoradiotherapy | PD-L1 ≥ 1% | |
| Paz-Ares et al. [80] | Metastatic SCLC | First line therapy in combination with carboplatin/cisplatin and etoposide | N/A | ||
| Burris et al. [81] | Irresectable or metastatic biliary tract carcinoma | First line therapy in combination with gemcitabine and cisplatin | N/A | ||
| Abou-Alfa et al. [82] | Advanced or unresectable hepatocellular carcinoma | First line therapy, in monotherapy | N/A | ||
| Anti-CTLA-4 | Ipilimumab | Hodi et al. [83] | Metastatic melanoma | N/A | N/A |
| Anti-CTLA-4 combined with another ICI | Nivolumab + ipilimumab | Larkin et al. [2] | Metastatic melanoma | N/A | N/A |
| Motzer et al. [84] | Metastatic renal carcinoma with intermediate-high risk | First line therapy | N/A | ||
| Baas et al. [85] | Unresectable malignant pleural mesothelioma | First line therapy | N/A | ||
| Kato et al. [86] | Advanced unresectable, recurrent or metastatic squamous cell esophageal carcinoma | First line therapy | PD-L1 ≥ 1% | ||
| Lenz et al. [87] | Metastatic colorectal carcinoma | Subsequent therapy after fluoropyrimidine-based chemotherapy | dMMR | ||
| Tremelimumab + durvalumab | Abou-Alfa et al. [82] | Advanced or unresectable hepatocellular carcinoma | First line therapy | N/A | |
| Tremelimumab + durvalumab + platinum-based chemotherapy | Johnson et al. [88] | Metastatic NSCLC | First line therapy | No EGFR or ALK mutations | |
ICIs: immune checkpoint inhibitors; PD-1: programmed cell death protein 1; PD-L1: programmed death ligand 1; NSCLC: non-small cell lung cancer; HER2: human epidermal growth factor receptor 2; CPS: combined positive score; EGFR: epidermal growth factor receptor; ALK: anaplastic lymphoma kinase; ROS1: ROS proto-oncogene 1 receptor tyrosine kinase. N/A: not applicable
