. 2018 Apr 9;7(5):R196–R211. doi: 10.1530/EC-18-0079
This work is licensed under a Table 3.
Dysthyroidism induced by PD-1 antibodies according to pathology type.
| Study (authors and publication year) | Study phase (or name) | Patient’s number | Pathology | Treatment | Hypothyroidism (%) | Hyperthyroidism (%) | Thyroiditis (%) |
|---|---|---|---|---|---|---|---|
| Robert et al. (2014) (34) | Phase 1 trial | 173 | Advanced melanoma which progressed after at least two ipilimumab doses | i.v. pembrolizumab at 2 mg/kg every 3 weeks or 10 mg/kg every 3 weeks | 4 | 1.7 | NR |
| Robert et al. (2015) (33) | Phase 3 study (KEYNOTE-006) | 834 | Advanced melanoma | 1:1:1 pembrolizumab 10 mg/kg every 2 weeks or every 3 weeks or four doses of ipilimumab 3 mg/kg every 3 weeks | 10.1/8.7/2 | 6.5/3.2/2.3 | NR |
| Garon et al. (2015) (38) | Phase 1 study (KEYNOTE-001) | 495 | Advanced NSCLC | Pembrolizumab 2 mg or 10 mg/kg every 3 weeks or 10 mg/kg every 2 weeks | 6.9 | 1.8 | NR |
| Ribas et al. (2016) (35) | Phase 1b study | 655 | Advanced or metastatic melanoma | Pembrolizumab 10 mg/kg/2 weeks, 10 mg/kg/3 weeks, or 2 mg/kg/3 weeks | 7 | 2 | 1 |
| Langer et al. (2016) (39) | Phase 2 study (KEYNOTE-021) | 123 | Stage IIIB or IV NSCLC without targetable EGFR or ALK genetic aberrations | 4 cycles of pembrolizumab 200 mg plus carboplatin AUC 5 mg/mL/min and pemetrexed 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months (60 patients) vs the same treatment without pembrolizumab (63 patients) | 15 (pembrolizumab + chemotherapy) | 8 (pembrolizumab + chemotherapy) | NR |
| Reck et al. (2016) (37) | Phase 3 study (KEYNOTE-024) | 305 | Previously untreated advanced NSCLC with PD-L1 expression ≥50% of tumor cells and no sensitizing mutation of the EGFR gene or translocation of the ALK gene | Pembrolizumab 200 mg every 3 weeks (154 patients) or the investigator’s choice of platinum-based chemotherapy (151 patients) | 9.1 | 7.8 | 2.6 |
| Seiwert et al. (2016) (40) | Phase 1b study (KEYNOTE-012) | 104 | Recurrent or metastatic squamous cell carcinoma of the head and neck | Pembrolizumab 10 mg/kg intravenously every 2 weeks | 7 | 2 | NR |
| Bellmunt et al. (2017) (43) | Phase 3 study (KEYNOTE-045) | 542 | Advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy | Pembrolizumab 200 mg every 3 weeks vs the investigator’s choice of chemotherapy with paclitaxel, docetaxel, or vinflunine | 6.4 | 3.8 | 0.8 |
| Topalian et al. (2012) (68) | Phase 1 study | 296 | Advanced melanoma, NSCLC, castration-resistant prostate cancer, or renal cell or colorectal cancer | Nivolumab 0.1–10.0 mg/kg every 2 weeks | 2 | 1 | NR |
| Topalian et al. (2014) (69) | Phase III trials | 107 | Advanced melanoma | Nivolumab i.v. 1, 3, or 10 mg/kg/2 weeks | 5.6 | 1.9 | NR |
| Borghaei et al. (2015) (25) | Phase III trials | 580 | NSCLC that had progressed during or after platinum-based doublet chemotherapy | Nivolumab at a dose of 3 mg/kg/2 weeks (292 patients) or docetaxel at a dose of 75 mg/m2 of body-surface area every 3 weeks (290 patients) | 7 | 1 | 0.34 |
| Larkin et al. (2015) (27) | Phase III trial (CheckMate 067) | 945 | Unresectable stage III or IV melanoma | 1:1:1 nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone | 8.6/15/4.2 | 4.2/9.9/1 | NR |
| Brahmer et al. (2015) (70) | Phase III trial (CheckMate 017) | 272 | Advanced NSCLC disease progression during or after first-line chemotherapy with limited treatment options | Nivolumab, at a dose of 3 mg/kg/2 weeks (135 patients), or docetaxel, at a dose of 75 mg/m2 of body-surface area every 3 weeks (137 patients) | 4/0 | NR | NR |
| Rizvi et al. (2015) (29) | Phase II trial (CheckMate 063) | 117 | Advanced, refractory, squamous non-small-cell lung cancer | Nivolumab i.v. 3 mg/kg every 2 weeks | 3 | 1 | 1 |
| Motzer et al. (2015) (26) | Phase III trial (CheckMate 025) | 821 | Advanced clear-cell RCC and previous treatment with one or two regimens of antiangiogenic therapy | 1:1 Nivolumab i.v. 3 mg/kg/2 weeks (410 patients) or a 10-mg everolimus tablet orally once daily (411 patients) | NR | NR | NR |
| Weber et al. (2015) (28) | Phase III trial (CheckMate 037) | 405 | Unresectable or metastatic melanoma, and progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if BRAFV600 mutation-positive | 2:1 Nivolumab i.v. 3 mg/kg/2 weeks (272 patients) or ICC (dacarbazine 1000 mg/m2/3 weeks or paclitaxel 175 mg/m2 combined with carboplatin area under the curve 6 every 3 weeks (133 patients) | 5.9/0 | 1.9/0 | NR |
| Ferris et al. (2016) (19) | Phase III trial (CheckMate 141) | 361 | Recurrent SCC of the head and neck with disease progression within 6 months after platinum-based chemotherapy | Nivolumab 3 mg/kg/2 weeks (240 patients) or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab) 121 patients | 3.8/0.9 | 0.8/0 | 0.8/0 |
| Sharma et al. (2017) (16) | Phase II trial (CheckMate 275) | 270 | Metastatic or surgically unresectable locally advanced urothelial carcinoma | Nivolumab 3 mg/kg intravenously every 2 weeks | 8 | NR | NR |
ALK, anaplastic lymphoma kinase; AUC, area under curve; EGFR, epidermal growth factor receptor; ICC, investigator’s choice of chemotherapy; i.v., intravenous; NCSLC, non-small-cell lung cancer; NR, not reported; RCC, renal cell carcinoma; SCC, squamous cell carcinoma.