Table I.
Characteristics and efficacy results of the eligible studies.
First author, year (trial) | Phase | Setting | Target population | Arms | Primary endpoints | SEPs | No. of enrolled patients | PFS (C vs. E) | OS (C vs. E) | ORR (C vs. E) | (Refs.) |
---|---|---|---|---|---|---|---|---|---|---|---|
Mettu et al, 2019 (BACCI) | 2, randomized | Metastatic, refractory | Not selected for MMR status | C: Capecitabine + bevacizumab + placebo; E: Capecitabine + bevacizumab + atezolizumab | PFS | ORR, OS, safety | 128 | 3.3 (95% CI, 2.1-6.2) vs. 4.4 (95% CI, 4.1-6.4) months; HR, 0.725 (95% CI, 0.491-1.07; P=0.051) | 12-month OS: 43% (95% CI, 29–63) vs. 52% (95% CI, 42–65); HR, 0.94 (95% CI, 0.56-1.56; P=0.4) | 4.35 (95% CI, 0.5-14.8) vs. 8.54% (95% CI, 3.5-16.8); P=0.5 | (36) |
Andre et al, 2021 (KEYNOTE-177) | 3 | Metastatic, 1st line | dMMR/MSI-H | C: SOC CT +/-bevaci zumab/cetuximab; E: Pembrolizumab | PFS, OS | ORR, safety | 307 | 8.2 vs. 16.5 months; HR, 0.59 (95% CI, 0.45-0.79) | 36.7 months vs. median not reached; HR, 0.74 (95% CI, 0.53-1.03; P=0.0359) | 33.1 vs. 45.1% | (16) |
Chen et al, 2020 (CCTG CO.26) | 2, randomized | Metastatic, refractory | Not selected for MMR status | C: BSC; E: Durvalumab + tremelimumab + BSC | OS | PFS, ORR, AEs | 180 | 1.9 vs. 1.8 months; HR, 1.01 (90% CI, 0.76-1.34; P=0.97) | 4.1 vs. 6.6 months; HR, 0.72 (90% CI, 0.54-0.97; P=0.07) | 0 vs. 0.84% (DCR: 6.6% vs. 22.7%; P=0.006) | (30) |
Grothey et al, 2018 (MODUL) | 2, randomized, signal-seeking trial | Metastatic, maintenance after 1st line | BRAF wild-type | C: Fluoropyrimidine + bevacizumab; E: Fluoropyrimidine + bevacizumab + atezolizumab | PFS | OS, AEs, ORR, DCR, TTR, DoR | 445 | 7.39 vs. 7.2 months; HR, 0.96 (95% CI, 0.77-1.20; P=0.727) | 21.91 vs. 22.05 months; HR, 0.86 (95% CI, 0.66-1.13; P=0.283) | Ongoing | (35) |
Eng et al, 2019 (COTEZO IMblaze370) | 3 | Metastatic, at least two prior regimens | Recruitment of patients with MSI-H was capped at 5% | C: Regorafenib; E1: Atezolizumab; E2: Atezolizumab + cobimetinib | OS | PFS, CR, PR, DoR, QoL, AEs, plasmatic concentration of atezolizumab and cobimetinib, % of anti-atezolizumab antibodies | 363 | C vs. E1: 2 (95% CI, 1.87-3.61) vs. 1.94 (95% CI, 1.91-2.1) months; HR, 1.39 (95% CI, 1–1.94; P=0.05); C vs. E2: 2 (95% CI, 1.87-3.61) vs. 1.91 (95% CI, 1.87-1.97) months; HR, 1.25 (95% CI, 0.94-1.65; P=0.13) | C vs. E1: 8.51 (95% CI, 6.41-10.71) vs. 7.10 (95% CI, 6.05-10.05) months; HR, 1.19 (95% CI, 0.83-1.71; P=0.34); C vs. E2: 8.51 (95% CI, 6.41-10.71) vs. 8.87 (95% CI, 7.00-10.61) months; HR, 1.00 (95% CI, 0.73-1.38; P=0.99) | Ongoing | (33) |
AE, adverse event; BSC, best supportive care; C, control arm; CI, confidence interval; CR, complete remission; CT, chemotherapy; DCR, disease control rate; dMMR, deficient mismatch repair; DoR, duration of response; E, experimental arm; HR, hazard ratio; MMR, mismatch repair; MSI-H, high microsatellite instability; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial remission; QoL, quality of life; SEP, secondary endpoint; SOC, standard of care; TTR, time to treatment response.