Table I.
Clinical studies of ICIs.
| Author/s | Year | Number of patients | ICI | Diagnosis | Trial name | Main conclusion | (Refs.) |
|---|---|---|---|---|---|---|---|
| Topalian et al | 2012 | 296 | BMS-936558, (anti-PD-1) | Advanced solid tumors | NCT00730639 | The ORR was ~1 in 4 to 1 in 5 and 14% of patients experienced grade 3 or 4 irAEs | (46) |
| Ott et al | 2017 | 75 | Pembrolizumab, (anti-PD-1) | Advanced endometrial cancer | NCT02054806 | The PR rates was achieved in 13.0% of the patients, and irAEs occurred in 54.2% of the patients | (47) |
| Antonia et al | 2019 | 304 | Durvalumab, (anti-PD-L1) | Stage IIIB-IV non-small cell lung cancer (NSCLC) | NCT01693562 | The ORR of patients with PD-L1 expression greater than or equal to 25% was 21.8%, and the ORR of patients with PD-L1 expression less than 25% was 6.4% irAEs occurred in 57.2% of patients | (48) |
| Schöffski et al | 2022 | 255 | Ieramilimab (anti-LAG-3) ± Spartalizumab (anti-PD-1) | Advanced solid tumors | NCT02460224 | Tumor responses occurred in 10% of patients. And irAEs occurred in 56 and 69% of patients in the ieramimab monotherapy and ieramimab plus Spartalizumab groups, respectively | (49) |
| Curigliano et al | 2021 | 219 | Sabatolimab (anti-TIM-3) ± Spartalizumab (anti-PD-1) | Advanced solid tumors | NCT02608268 | The partial response rates occurred in 6% of patients receiving combination therapy, and irAEs occurred in 48% | (50) |
| Kelly et al | 2023 | 30 | Epacadostat (anti-IDO1-) Pembrolizumab4 (anti-PD-1) | Advanced sarcoma | N | The ORR was 3.3, and 23% of patients experienced grade 3 irAEs | (51) |
| Zakharia et al | 2021 | 131 | Indoximod (anti-IDO1-) + Pembrolizumab4 (anti-PD-1) | Advanced melanoma | N | The ORR of the evaluable population was 51%, and the most common irAE was fatigue, with an incidence of 62.3% | (52) |
| Lynch et al | 2012 | 204 | Ipilimumab (anti-CTLA-4) + Paclitaxel and Carboplatin | Stage IIIB/IV NSCLC | N | The immune-related best response rates for staged ipilimumab, concurrent ipilimumab, and control therapy were 32, 21, and 18%, respectively. The overall incidence of grade 3 and 4 irAEs was 15, 20, and 6% in the staged ipilimumab, concurrent ipilimumab, and control groups, respectively | (53) |
| Wolchok et al | 2018 | 945 | Ipilimumab (anti-CTLA-4) ± Nivolumab (anti-PD-1) | Advanced melanoma | N | At 3 years, the OS rates were 58% with nivolumab plus ipilimumab, 52% with nivolumab alone, and 34% with ipilimumab alone | (54) |
| Hellmann et al | 2018 | 2,877 | Ipilimumab (anti-CTLA-4) + Nivolumab (anti-PD-1) | Stage IV or recurrent NSCLC | NCT02477826 | The ORR for nivolumab plus ipilimumab was 45.3%, and the incidence of grade 3 or 4 irAEs related to nivolumab plus ipilimumab was 31.2% | (55) |
| Tannir et al | 2021 | 1,096 | Ipilimumab (anti-CTLA-4) + Nivolumab (anti-PD-1) vs. Sunitinib | Advanced renal cell carcinoma with sarco-matoid features | N | The ORR with ipilimumab plus nivolumab was 60.8%, and grade 3 or 4 irAEs occurred in 49% | (56) |
| Rini et al | 2019 | 915 | Atezolizumab (anti-PD-L1) + Bevacizumab vs. Sunitinib | Metastatic renal cell carcinoma | NCT02420821 | Grade 3–4 irAEs occurred in 40% of the atezolizumab plus bevacizumab group | (57) |
| Garon et al | 2019 | 550 | Pembrolizumab (anti-PD-1) | Advanced programmed PD-L1 NSCLC | N | The estimated 5-year OS was 23.2% for treatment-naive patients and 15.5% for previously treated patients, and the incidence of irAEs was 71% | (58) |
| Yuan et al | 2023 | 72 | Camrelizumab (anti-PD-1) + Apatinib | Recurrent/metastatic nasopharyngeal carcinoma | NCT04547088 NCT04548271 | The ORR of the platinum-resistant cohort was 65%, and the ORR of the PD-1 inhibi-tor-resistant cohort was 34.3, and 65.3% of the patients developed ≥ grade 3 irAEs | (59) |
| Liu et al | 2023 | 20 | Camrelizumab (anti-PD-1) + Apatinib | Relapsed or refractory peripheral T-cell lymphoma | N | The ORR for all patients was 30%, and grade 3 or higher adverse events were hyperlipidemia (15%), hypokalemia (15%), and anemia (15%) | (60) |
| Zhao et al | 2023 | 53 | Cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) | Metastatic NSCLC | NCT04172454 | The ORR of patients who had previously received platinum-based two-agent chemotherapy failure was 10, and 11.3% of patients had grade 3–4 irAEs | (61) |
ICI, immune checkpoint inhibitors; PD-1, programmed cell death protein 1; PD-L1, programmed cell cell death protein ligand 1; PFS, progression-free survival; NSCLC, non-small cell lung cancer; OS, overall survival. ORR, objective response rate; PR, partial response.