List of checkpoint inhibitors and their uses, with notable adverse effects (Continued)
| Drug | Mechanism | Cancer sites with EMA approval for treatment | Notable adverse effects | Notable endocrine effects 10,14,16 | Dose-dependent adverse effects? | Other comments |
|---|---|---|---|---|---|---|
| Ipilimumab (Yervoy) | Anti-CTLA-4 mAb | Melanoma | >10% fatigue/rash/diarrhoea | Greater risk of hypophysitis than other monotherapy (3%) 2–5% thyroid dysfunction 1% adrenal insufficiency | Yes | Inferior effects on survival compared with other checkpoint inhibitor monotherapy or combination |
| Tremelimumab | Anti-CTLA-4 mAb | Not approved by EMA/FDA currently | Less known, likely similar to ipilimumab | Yes | Granted ODD by FDA for treating HCC in combination with durvalumab | |
| Pembrolizumab (Keytruda) | Anti-PD-1 mAb | Melanoma NSCLC (PD-1 expressing or non-squamous) Hodgkin’s lymphoma Urothelial RCC Head and neck SCC CRC (with MMR/MSI) | >20% fatigue/nausea/diarrhoea 34% skin effects 3 | 5–10% thyroid dysfunction Greater risk of hyperthyroid compared with anti-PD-L-1 Highest incidence diabetes mellitus (1%) 1% adrenal insufficiency | No | Patients with tumours expressing high PD-L-1 levels have a better response and this is used to stratify treatment choice in NSCLC |
| Nivolumab (Opdivo) | Anti-PD-1 mAb | Melanoma NSCLC Hodgkin’s lymphoma Urothelial RCC Head and neck SCC | >10% fatigue/nausea/appetite loss 34% skin effects 3 | 5–10% thyroid dysfunction (greater risk of hyperthyroid compared with anti-PD-L-1) 0.5–1% diabetes mellitus 1% adrenal insufficiency | No | Studies proving benefit after failure of platinum-based chemotherapy |
| Atezolizumab (Tecentriq) | Anti-PD-L-1 mAb | NSCLC and SC lung cancer Breast cancer (triple negative) Urothelial | >10% fatigue/arthralgia/nausea/rash/diarrhoea | Most associated with adrenal insufficiency (1–2%) Fewer other endocrinopathies than other drugs | No | Generally for advanced or metastatic disease, proven to improve survival particularly in combination with chemotherapy |
| Avelumab (Bavencio) | Anti-PD-L-1 mAb | Merkel cell carcinoma RCC | >10% fatigue/nausea/diarrhoea/constipation | 1% diabetes mellitus Fewer adrenal effects than other anti-PD-L-1 mAb | No | Granted conditional marketing authorisation in EU in 2017, awaiting further clinical evidence |
| Durvalumab (Imfinzi) | Anti-PD-L-1 mAb | NSCLC | >20% rash/cough/ENT infections >10% drug-related pneumonia | 1% diabetes mellitus 1% adrenal insufficiency Greater thyroid dysfunction than other PD-L-1 mAb | No | Used when tumours express high PD-L-1 levels |
| Ipilimumab and nivolumab | Anti-CTLA-4 mAb and anti-PD-1 mAb | Melanoma RCC Head and neck SCC | >50% fever, fatigue, rash Greater incidence of all immune-related adverse effects | 20% thyroid dysfunction 6% hypophysitis 5–7% adrenal insufficiency | Yes | Used for high-risk RCC as first line, and for melanoma with low PD-L-1 expression. Generally more effective than monotherapy |
Unless specified above, information from EMA website.10 CRC = colorectal cancer; CTLA-4 = cytotoxic T-lymphocyte antigen 4; ENT = ear, nose and throat; EMA = European Medicines Agency; EU = European Union; FDA = US Food and Drug Administration; HCC = hepatocellular carcinoma; mAb = monoclonal antibody; MMR = mismatch repair gene; MSI = microsatellite instability; NSCLC = non-small cell lung cancer; ODD = orphan drug designation; PD-1 = programmed cell death protein 1; PD-L-1 = programmed cell death protein ligand 1; RCC = renal cell cancer; SCC = squamous cell carcinoma.