Table 1.
Characteristics of the 41 studies included in the qualitative data synthesis.
| Study characteristics |
Primary outcomes |
Secondary outcomes |
Methodological quality | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Author | Registration ID | Study design | Sample size | Location | Intervention (mg/kg) | Line of immunotherapy | ORR (%) | CR (%) | PR (%) | mPFS (months) | mOS (months) | 1-year PFS (%) | 1-year OS (%) | All grades irAEs (%) | Grade 3+ irAEs (%) | |
| D’Angelo et al.17 |
NCT01927419 NCT01844505 |
Pooled analysis of CheckMate 067 and CheckMate 069 | 36 | North America, Europe, Australia | Ipilimumab (3) | 1 | 8.3 (95% CI 1.8–22.5) | 0 | 8.3 | 2.7 (95% CI 2.6–2.8) | NR | NR | NR | NR | NR | Good |
| Zimmer et al.18 | NCT01355120 | Open-label, multi-center, single-arm phase II study (DeCOG) | 7 | Germany | Ipilimumab (3) | 2/3 | 17 | 0 | 17 | NR | 9.6 (95% CI 1.6–11.1) | NR | 14 | 29 | 14 | Fair |
| Del Vecchio et al.19 | NR | Expanded Access Program | 71 | Italy | Ipilimumab (3) | 1/2/3 | 12 | 1 | 10 | 4.3 (95% CI 3.4–5.2) | 6.4 | 15 | 35 | 35 | 9 | Fair |
| Rapoport et al.20 | NR | Expanded Access Program | 12 | South Africa | Ipilimumab (3) | 2+ | 0 | 0 | 0 | NR | NR | 0 | NR | NR | NR | Fair |
| Shaw et al.21 | NR | Expanded Access Program | 4 | UK | Ipilimumab (3) | 2+ | 0 | 0 | 0 | 3 | NR | NR | NR | NR | NR | Poor |
| Alexander et al.22 | NR | Named Patient Program | 8 | Australia | Ipilimumab (3) | 2+ | NR | NR | NR | 2.7 (95% CI 0.5–3.9) | 5.8 (95% CI 1.1–not reached) | 0 | 20 | NR | NR | Poor |
| Mignard et al.23 | NR | Multi-center, retrospective study | 76 | France | Ipilimumab (3) | 1/2 | 3.9 (95% CI 0.8–11.1) | NR | NR | NR | NR | NR | NR | NR | 26.3 | Fair |
| Postow et al.24 | NR | Multi-center, retrospective study | 33 | USA | Ipilimumab (3/10) | 1/2/3/4 | 6.7 (95% CI 0.8–22.1) | 3.4 | 3.4 | NR | 6.4 | 10 | NR | 38 | 6 | Fair |
| Arzu Yasar et al.25 | NR | Multi-center, retrospective study | 11 | Turkey | Ipilimumab (NR) | 1/2/3+ | NR | NR | NR | NR | 6.9 (95% CI 4.5–9.3) | NR | NR | NR | NR | Poor |
| Moya-Plana et al.26 | NR | Single-center, prospective study | 24 | France | Ipilimumab (3) | 1 | 8.2 | 4.1 | 4.1 | 3 (95% CI 2.5–4.6) | 12 (95% CI 5.9–26.9) | 8 | 54 | NR | 12.5 | Fair |
| Schaefer et al.27 | NR | Single-center, retrospective study | 8 | Germany | Ipilimumab (NR) | NR | 12.5 | 0 | 12.5 | NR | NR | NR | NR | NR | NR | Poor |
| Saijo et al.28 | NR | Single-center, retrospective study | 7 | Japan | Ipilimumab (3) | 2+ | 0 | 0 | 0 | 6.4 | 22 | 0 | NR | 100 | 71.4 | Poor |
| Quereux et al.29 | NR | Single-center, retrospective study | 6 | France | Ipilimumab (3) | 1/2 | 16.7 | 0 | 16.7 | NR | NR | 0 | 33 | 66.7 | 16.7 | Poor |
| Kiyohara et al.30 | NR | Ongoing, prospective, postmarketing surveillance observational study | 208 | Japan | Nivolumab (2) | 2/3/4+ | NR | NR | NR | NR | 11.3 | NR | NR | 53.4 | NR | Poor |
| D’Angelo et al.17 |
NCT00730639 NCT01621490 NCT01721772 NCT01721746 NCT01844505 |
Pooled analysis of CA209-003, CA209-038, CheckMate 066, CheckMate 037, and CheckMate 067 | 86 | North America, Europe, Australia | Nivolumab (3) | 1/2+ | 23.3 (95% CI 14.8–33.6) | 5.8 | 17.4 | 3.0 (95% CI 2.2–not reached) | NR | 27 | NR | 66.3 | 8.1 | Fair |
| Nathan et al.31 | NCT02156804 | Single-arm, open-label, multi-center phase II study (CheckMate 172) | 63 | Europe | Nivolumab (3) | 2/3/4+ | NR | NR | NR | NR | 11.5 (95% CI 6.4–15.0) | NR | 47.2 | 66.7 | 20.6 | Good |
| Nomura et al.32 | UMIN000015845 | Single-arm, open-label, multi-center phase II study | 17 | Japan | Nivolumab (2) | 1/2 | 23.5 (95% CI 6.8–49.9) | 5.9 | 17.6 | 1.4 (95% CI 1.2–2.8) | 12.0 (95% CI 3.5–not reached) | 17.6 | 50.0 | 70 | 15 | Good |
| Yamazaki et al.33 | JapicCTI-142533 | Single-arm, open-label, multi-center phase II study | 6 | Japan | Nivolumab (3) | 1 | 33.3 | 0 | 33.3 | NR | 12 | 16.7 | 50 | NR | NR | Fair |
| Takahashi et al.34 | NR | Single-center, retrospective study | 27 | Japan | Nivolumab (2) | NR | 33.3 | 7.4 | 25.9 | NR | NR | NR | NR | NR | NR | Poor |
| Otsuka et al.35 | NR | Single-center, retrospective study | 27 | Japan | Nivolumab (2) | 1/2+ | 30 | 11 | 19 | NR | NR | NR | NR | 59 | 11 | Poor |
| Maeda et al.36 | NR | Single-center, retrospective study | 24 | Japan | Nivolumab (NR) | NR | 20.8 | 0 | 20.8 | 7.5 | 14.1 | NR | NR | NR | NR | Poor |
| Kondo et al.37 | NR | Single-center, retrospective study | 22 | Japan | Nivolumab (2/3) | 1/2 | 9.5 | NR | NR | NR | NR | NR | NR | NR | NR | Fair |
| Koyama et al.38 | NR | Single-center, retrospective study | 21 | Japan | Nivolumab (NR) | 1 | 19 (95% CI 35–77) | NR | NR | 2.1 | 8.2 | 6.6 | 59 | 29 | 4.8 | Poor |
| Quereux et al.29 | NR | Single-center, retrospective study | 8 | France | Nivolumab (3) | 1/2 | 50 | 0 | 50 | 9 | NR | 0 | 86 | 100 | 0 | Poor |
| Urasaki et al.39 | NR | Single-center, retrospective study | 8 | Japan | Nivolumab (NR) | 2 | 37.5 | 25 | 12.5 | 10.2 | Not reached | NR | NR | 87.5 | 0 | Poor |
| Hamid et al.40 |
NCT01295827 NCT01704287 NCT01866319 |
Post-hoc analysis of KEYNOTE-001, 002, 006 | 84 | North America, Europe, Australia | Pembrolizumab (2) | 1/2/3/4+ | 19 (95% CI 11–29) | NR | NR | 2.8 (95% CI 2.7–2.8) | 11.3 (95% CI 7.7–16.6) | 0 | 45.2 | 73 | 10 | Good |
| Si et al.41 | NCT02821000 | Phase Ib study (KEYNOTE-151) | 15 | China | Pembrolizumab (2) | 2 | 13.3 (95% CI 1.7–40.5) | 6.7 | 6.7 | NR | NR | NR | NR | NR | NR | Good |
| Yamazaki et al.42 | NCT02180061 | Phase Ib study (KEYNOTE-041) | 8 | Japan | Pembrolizumab (2) | 1/2/3 | 25.0 (95% CI 3.2–65.1) | 0 | 25 | 3.4 (95% CI 2.1–not reached) | Not reached | 25 | 51.4 | 100 | 50 | Good |
| Moya-Plana et al.26 | NR | Single-center, prospective study | 20 | France | Pembrolizumab (2) | 1 | 35 | 20 | 15 | 5 (95% CI 2.6–33.1) | 16.2 (95% CI 5.3–42.6) | 38 | 57 | NR | 5 | Fair |
| Mignard et al.23 | NR | Multi-center, retrospective study | 75 | France | Nivolumab (3) or Pembrolizumab (2) | 1/2 | 20 (95% CI 11.6–30.8) | NR | NR | NR | NR | NR | NR | NR | 18.7 | Fair |
| Shoushtari et al.43 | NR | Multi-center, retrospective study | 35 | USA | Nivolumab (0.3–10) or Pembrolizumab (2/10) | 1/2+ | 23 (95% CI 10–40) | 0 | 23 | 3.9 | 12.4 | ~20 | NR | NR | NR | Fair |
| Ogata et al.44 | NR | Single-center, retrospective study | 59 | USA | Nivolumab (NR) or Pembrolizumab (NR) | 1/2+ | 16.7 | NR | NR | 3.0 | 20.1 | NR | NR | NR | NR | Poor |
| Tian et al.45 | NR | Single-center, retrospective study | 9 | USA | Nivolumab (NR) or Pembrolizumab (NR) | NR | 50 | 16.7 | 33.3 | NR | NR | NR | NR | NR | NR | Poor |
| Schaefer et al.27 | NR | Single-center, retrospective study | 7 | Germany | Nivolumab (NR) or Pembrolizumab (NR) | NR | 28.6 | 0 | 28.6 | NR | NR | NR | NR | NR | NR | Poor |
| Chi et al.46 | NCT03013101 | Multi-center, open-label, phase II study | 21 | China | Toripalimab (3) | 2/3/4/5+ | 0 | 0 | 0 | NR | NR | 0 | NR | NR | NR | Fair |
| D’Angelo et al.17 |
NCT01927419 NCT01844505 |
Pooled analysis of CheckMate 067 and CheckMate 069 | 35 | North America, Europe, Australia | Ipilimumab (3) + Nivolumab (1) | 1 | 37.1 (95% CI 21.5–55.1) | 2.9 | 34.3 | 5.9 (95% CI 2.2–5.4) | NR | 32 | NR | 97.1 | 40 | Good |
| Namikawa et al.47 | JapicCTI-152869 | Single-arm, open-label, multi-center phase II study | 12 | Japan | Ipilimumab (3) + Nivolumab (1) | 1 | 33.3 | 0 | 33.3 | Not reached | Not reached | 54.7 | 75 | NR | NR | Fair |
| Sheng et al.48 | NCT03086174 | Open-label, phase Ib study | 33 | China | Toripalimab (1/3) + Axitinib (5 mg) | 1/2 | 48.3 (95% CI 29.4–67.5) | 0 | 48.3 | 7.5 (95% CI 3.7–not reached) | >18 | 41.4 | 65.5 | 97.0 (treatment-related) | 39.4 (treatment-related) | Fair |
| Kim et al.49 | NR | Single-center, retrospective study | 12 | Korea | Pembrolizumab (2) + Radiotherapy (20–69 Gy) | 1/2+ | 66.7 | 8.3 | 58.3 | <6 | >36 | 0 | 100 | NR | NR | Poor |
| Hanaoka et al.50 | NR | Single-center, retrospective study | 10 | Japan | Nivolumab (3) or Pembrolizumab (2) + Radiotherapy (30–70 Gy) | NR | NR | NR | NR | 7.4 | Not reached | 20 | 64.3 | NR | NR | Poor |
| Kato et al.51 | NR | Single-center, retrospective study | 7 | Japan | Nivolumab (2/3) or Pembrolizumab (2) + Radiotherapy (30–60+ Gy) | NR | 57.1 | 28.6 | 28.6 | NR | NR | 50 | NR | NR | 0 | Poor |
NR: not reported.