Table 2.
Clinical trials' efficacy data of ICIs in patients with SCLC.
| Agent | Trial | Phase | Line of therapy | Population | Treatment arms | Primary end point | Secondary end points | Median follow-up time | Publish year |
|---|---|---|---|---|---|---|---|---|---|
| Nivolumab | CheckMate032 (NCT01928394) | Phase I/II | Third or later line | SCLC | NIvolumab 3 mg/kg | ORR: 11.9% (95% CI: 6.5–19.5) | mDOR: 17.9 m (95% CI:3.0–42.1); mOS: 5.6 m (95% CI: 3.1–6.8); mPFS: 1.4 m (95% CI: 1.3–1.6) | 28.3 m | 2018 |
| CheckMate331 (NCT02481830) | Phaseiii | Second line | Relapsed SCLC | Nivolumab 240 mg | mOS: 7.46 m (95% CI: 5.65–9.20) | mPFS: 1.45 m (95% CI:1.41- 1.51); ORR: 13.7% (95% CI:10.0–18.3); DOR:72% | 15.8 m | 2018 | |
| Pembrolizumab | KEYNOTE028 (NCT02054806) | Phase Ib | Third line | ES-SCLC | Pembrolizumab 10 mg/kg | ORR: 33% (95 CI: 16–55%) | mDOR: 19.4 m (95% CI:3.6–20.0); mPFS:1.9 m (95% CI:1.7–5.9); mOS: 9.7 m (95% CI: 4.1- not reached). | 9.8 m | 2017 |
| KEYNOTE158 (NCT02628067) | Phase II | Third line | ES-SCLC | Pembrolizumab 200 mg | ORR: 18.7% (95% CI: 11.8% −27.4%) | mPFS: 2.0 m (95%CI: 1.9–2.1); mOS: 8.7 m (95% CI: 5.6–12) | 10.1 m | 2018 | |
| pool analysis of KEYNOTE028 and KEYNOTE158 | Phase Ib/phase II | Third line | ES-SCLC | Pembrolizumab 10 mg/kg or 200 mg | ORR: 19.3% (95% CI: 11.4–29.4%) | mPFS: 2.0 m (95% CI: 1.9–3.4); mOS:7.7 m (95% CI: 5.2–10.1) | 25.9 m | 2020 | |
| Gadgeel et al. (48) | Phase II | Maintenance therapy | ES-SCLC | Pembrolizumab 200 mg | mPFS: 1.4 m (95% CI: 1.3–2.8) | mOS: 9.6 m (95% CI: 7.0–12) | 5 w | 2018 | |
| NCT02402920 | Phase I | Second line | ES-SCLC | 45 Gy thoracic radiotherapy +pembrolizumab 50–200 mg | Safety | mPFS: 6.1 m (95% CI 4.1–8); mOS: 8.4 m (95%; CI: 6.7–10.1) | 7.3 m | 2020 | |
| Welsh et al. (49) | phase I/II | - | LS-SCLC | Concurrent chemoradiotherapy +pembrolizumab 100–200 mg | Safety | mPFS:19.7 m (95% CI 8.8–30.5); mOS:39.5 months (95% CI:8.0–71.0) | 23.1 m | 2020 | |
| NCT02551432 | Phase II | Second line | ES-SCLC | Paclitaxel +pembrolizumab 200 mg | ORR: 23.1% (95% CI: 6.9–39.3) | mPFS: 5.0 m (95% CI: 2.7–6.7); mOS:9.1m (95% CI: 6.5–15.0) | 11.1 m | 2019 | |
| KEYNOTE604 (NCT03066778) | Phase III | First line | ES-SCLC | Pembrolizumab 200 mg + etoposide+platinum | mPFS: 4.5 m (95% CI: 4.3–5.4); mOS: 10.8 m (95% CI: 9.2–12.9) | ORR: 70.6% (95% CI: 64.2–76.4); mDOR: 4.2 m (95% CI:1.01–26.01) | 22 m | 2020 | |
| Placebo + etoposide +platinum | mPFS: 4.3 m (95% CI: 4.2–4.4); mOS: 9.7 m (95% CI: 8.6–10.7) | ORR: 61.8% (95% CI: 55.1–68.2); mDOR: 3.7 m (95% CI:1.41–25.81) | |||||||
| Tislelizumab | NCT03432598 | Phase II | First line | ES-SCLC | Tislelizumab 200 mg + etoposide+platinum | ORR: 77% (95% CI: 50.1–93.2) | mPFS: 6.9 m (95% CI: 4.9–10.09) | 15.3 m | 2020 |
| Atezolizumab | NCT01375842 | Phase Ia | First line | ES-SCLC | Atezolizumab 15 mg/kg or 1200 mg | Safety | ORR: 6%; mPFS: 1.5 m (95% CI: 1.2–2.7); mOS: 5.9 m (95% CI: 4.3–20.1) | 6.7 m | 2016 |
| IMpower133 (NCT02763579) | Phase I/III | First line | ES-SCLC | Atezolizumab 1,200 mg+carboplatin + etoposide | mOS: 12.3 m (95% CI:10.8–15.9); mPFS:5.2 m (95% CI: 4.4–5.6) | ORR: 60.2% (95% CI:53.1–67.0); DOR: 4.2 m (95%CI: 1.4+ −19.5) | 13.9 m | 2018 | |
| Placebo+ carboplatin+ etoposide | mOS:10.3 m (95% CI: 9.3–11.3); mPFS: 4.3 m (95% CI: 4.2–4.5) | ORR: 64.4% (95% CI: 57.3–71.0); DOR: 3.9 m (95% CI:2.0–16.1+) | |||||||
| IFCT-1603 (NCT03059667) | Phase II | Second line | relapsed ES-SCLC | Atezolizumab 1,200 mg | ORR: 2.3% (95% CI: 0.0–6.8) | mPFS:1.4 m (95%CI: 1.2–1.5); mOS: 9.5 m (95% CI: 3.2–14.4) | 13.7 m | 2019 | |
| Chemotherapy | ORR: 10% (95% CI: 0.0–23.1) | mPFS:4.3 m (95%CI: 1.5–5.9); mOS:8.7m (95% CI:4.1–12.7) | |||||||
| Durvalumab | CASPIAN (NCT03043872) | Phase III | First line | ES-SCLC | Durvalumab 1,500 mg + etoposide+ platinum | mOS: 13.0 m (95% CI: 11.5–14.8) | mPFS: 5.1 m(95% CI 4.7–6.2); ORR: 68% | 14.2 m | 2019 |
| Etoposide+platinum | mOS: 10.3 m (95%CI: 9.3–11.2) | mPFS: 5.4 m (95% CI:4.8–6.2); ORR: 58% | |||||||
| Goldman et al. (36) | Phase I/II | Second line | Relapsed SCLC | Durvalumab 10 mg/kg | Safety | ORR: 9.5% (95% CI: 1.2–30.4); mPFS: 1.5 m (95% CI: 0.9–1.8); mOS: 4.8 m (95% CI: 1.3–10.4) | NA | 2018 | |
| Ipilimumab | CA184-041 (NCT00527735) | Phase II | First line | ES-SCLC | Placebo/ paclitaxel /carboplatin | irPFS: 5.3 m | mOS: 9.9 m; irBORR: 53% (95% CI: 38–68%); irDCR: 96% (95% CI: 85–100%) | 11.1 m | 2013 |
| Ipilimumab 10 mg/kg/placebo+ paclitaxel/ carboplatin(concurrent) | irPFS: 5.7 m | mOS: 9.1 m; irBORR: 49% (95% CI: 33–65%); irDCR: 81% (95% CI: 67–92%) | |||||||
| Ipilimumab 10 mg/kg/placebo+ paclitaxel/ carboplatin(phased) | irPFS: 6.4 m | mOS: 12.9 m; irBORR: 71% (95% CI: 55%- 84%); irDCR: 93% (95% CI: 81–99%) | |||||||
| NCT01331525 | Phase II | First line | ES-SCLC | Ipilimumab 10 mg/kg+ carboplatin+ etoposide | not meet | mPFS: 6.9 m (95%CI: 5.5–7.9); mOS: 17.0 m (95% CI: 7.9–24.3); median irPFS:7.3 m (95% CI: 5.5–8.8) | 8.5 m | 2016 | |
| NCT01450761 | Phase III | First line | ES-SCLC | Ipilimumab 10 mg/kg+etoposide +platinum (cisplatin+ carboplatin) | mOS: 11.0 m | mPFS: 4.6 m; mDOR: 4.01 (95% CI: 3.32–4.17) | 10.5 m | 2016 | |
| Placebo+ etoposide+ platinum (cisplatin+ carboplatin) | mOS: 10.9 m | mPFS: 4.4 m; mDOR: 3.45 m (95% CI: 3.25–4.07) | 10.2 m | ||||||
| Nivolumab +ipilimumab | CheckMate451 (NCT02538666) | Phase III | Maintenance therapy | Relapsed ES-SCLC | Nivolumab 1 mg/kg + ipilimumab 3 mg/kg | mOS: 9.17 m (95% CI:8.15–10.25) | mPFS: 1.74 (95% CI: 1.48–2.63) | 9 m | 2019 |
| Nivolumab 1 mg/kg | mOS: 10.41 m (95% CI:9.46–12.12) | mPFS: 1.87 (95% CI: 1.61–2.63) | |||||||
| Placebo | mOS: 9.56 m (95% CI:8.18–11.01) | mPFS: 1.45 (95% CI: 1.41–1.48) | |||||||
| CheckMate032 (NCT01928394) | Phase I/II | Second or later line | SCLC | Nivolumab 3mg/kg | ORR:10% | mOS: 4.4 m (95% CI: 3.0–9.3); mPFS: 1.4 m (95% CI: 1.4–1.9) | 198.5 d | 2016 | |
| Nivolumab 1 mg/kg + ipilimumab 3 mg/kg | ORR:23% | mOS: 7.7 m (95% CI: 3.6–18.0); mPFS: 2.6 m (95% CI: 1.4–4.1) | 361.0 d | ||||||
| Nivolumab 3 mg/kg + ipilimumab 1 mg/kg | ORR:19% | mOS: 6.0 m (95% CI: 3.6–11.0); mPFS: 1.4 m (95% CI: 1.3–2.2) | 260.5 d | ||||||
| Durvalumab+ tremelimumab | NCT02261220 | Phase I | Third line | ES-SCLC | Durvalumab 20 mg/kg+tremelimumab 1 mg/kg | safety | ORR: 13.3%; DOR: 18.9 m (95% CI: 16.3–18.9); mPFS: 1.8 m (95% CI: 1.0–1.9); mOS: 7.9 m (95% CI: 3.2–15.8) | NR | 2018 |
| BALTIC (NCT02937818) | Phase II | First line | ES-SCLC | Durvalumab 1,500 mg + tremelimumab 75 mg | ORR: 9.5% (95% CI: 1.17–30.38) | 12 weeks DCR: 38.1% | 14 w | 2018 | |
| Durvalumab+ tremelimumab | CASPIAN (NCT03043872) | Phase III | First line | ES-SCLC | durvalumab 1,500 mg + tremelimumab 75 mg+platinum +etoposide | mOS: 10.4 m (95% CI 9.6–12.0) | mPFS: 4.9 m (95% CI 4.7–5.9); unconfirmed objective response: 74% | 25.1 m | 2021 |
| Durvalumab 1,500 mg+platinum +etoposide | mOS: 12.9 m (95% CI: 11.3–14.7) | mPFS: 5.1 m (95% CI 4.7–6.2); unconfirmed objective response: 79% | |||||||
| Platinum+ etoposide | mOS: 10.5 m (95%CI: 9.3–11.2) | mPFS: 5.4 m (95% CI 4.8–6.2); unconfirmed objective response: 71% |
mDOR, median disease control rate; mOS, median overall survival; mPFS, median progression-free survival; ORR, overall response rate; irPFS, immune-related progression-free survival; irBORR, immune related best overall response rate; irDCR, immune related disease control rate; +, denotes a censored observation; NA, not available.