Table 1. Characteristics of the studies included in this present meta-analysis.
| NRG-GY018 | RUBY | AtTEnd | DUO-E | MITO END-3 | |
|---|---|---|---|---|---|
| Phase | III | III | III | III | II |
| N | 816 (dMMR: 225 | pMMR 591) | 494 (dMMR: 118 | pMMR 376) | 551 (dMMR: 125 | pMMR 426) | 479* (dMMR: 95 | pMMR 384) *Excluding Durva + Ola |
125 (dMMR: 57 | pMMR 68) |
| Primary end point | PFS in the cohort dMMR and pMMR | PFS dMMR → PFS ITT → OS ITT (hierarchically tested) | PFS dMMR → PFS ITT → OS ITT (hierarchically tested) | PFS ITT (Durva vs. control) | PFS ITT |
| Pts | Measurable disease (stage III- IVA) or stage IVB or recurrent EC | Primary advanced stage III-IV or first recurrent EC | Stage III-IV newly diagnosed or recurrent EC | Stage III-IV or recurrent EC |
Stage III–IV or recurrent EC |
| First line | Paclitaxel + carboplatin + pembrolizumab/placebo for 6 cycles (q3w), followed by pembrolizumab/placebo for up to 14 cycles (q6w) |
Paclitaxel + carboplatin + dostarlimab/placebo for 6 cycles (q3w), followed by dostarlimab/placebo for up to 3 years (q6w) |
Paclitaxel + carboplatin + atezolizumab/placebo for 6 cycles (q3w), followed by atezolizumab/placebo until PD or unacceptable toxicity |
Paclitaxel + carboplatin + durvalumab/placebo for 6 cycles (q3w), followed by durvalumab/placebo or durvalumab + olaparib until PD or unacceptable toxicity (q4w) | Paclitaxel + carboplatin + avelumab/placebo for 6 cycles (q3w), followed by avelumab/placebo until PD or unacceptable toxicity (q2w) |
| Median FUP | 12 months in the dMMR cohort and 7.9 months in the pMMR | 24.8 months in the dMMR population and 25.4 months in the ITT | 26.2 months in the dMMR population and 28.3 months in the ITT | 16.4 months in the control arm and 17.1 months in Durva arm | 23.3 months for both arms |
| PFS ITT | NR | HR 0.64 95% CI: 0.51-0.80 |
HR 0.74 95% CI: 0.61-0.91 |
HR 0.71 95% CI: 0.57–0.89 |
HR 0.78 95% CI: 0.65–0.93 |
| PFS dMMR | HR 0.30 95% CI: 0.19-0.48 |
HR 0.28 95% CI: 0.16-0.50 |
HR 0.36 95% CI: 0.23-0.57 |
HR 0.42 95% CI: 0.22–0.80 |
HR 0.46 95% CI: 0.22-0.94 |
| PFS pMMR | HR 0.54 95% CI: 0.41-0.71 |
HR 0.76 95% CI: 0.59-0.98 |
HR 0.92 95% CI: 0.73-1.16 |
HR 0.77 95% CI: 0.60–0.97 |
HR 1.17 95% CI: 0.65-2.10 |
| OS ITT | NR | HR 0.69 95% CI: 0.54-0.89 |
HR 0.82 95% CI: 0.63-1.07 |
HR 0.77 95% CI: 0.56–1.07 |
HR 1.13 95% CI: 0.62–2.07 |
| OS dMMR | HR 0.55 95% CI: 0.25 - 1.19 |
HR 0.32 95% CI: 0.17-0.63 |
HR 0.41 95% CI: 0.22-0.76) |
HR 0.34 95% CI: 0.13-0.79 |
NR |
| OS pMMR | HR 0.79 95% CI: 0.53 - 1.17 |
HR 0.79 95% CI: 0.60-1.04 |
HR 1.00 95% CI: 0.74-1.35 |
HR 0.91 95% CI: 0.64-1.30 |
NR |
Abbreviations: N = Number of patients, PFS = progression-free survival, OS = Overall survival, ITT = Intention to treat, pMMR = mismatch repair–proficient, dMMR = mismatch repair–deficient, pts = patients, q2w = every 2 weeks, q3w = every 3 weeks, q4w = every 4 weeks; q6w = every 6 weeks; w = weeks, HR = Hazard ratio, 95% CI = 95% Confidence interval, FUP = follow-up; NR = not reported; placebo = plb; Durva = Durvalumab; Ola = Olaparib; PD = progressive disease