Table 1.
Summary of available evidence on PD-L1 evaluation in clinical trials testing immunotherapy in triple-negative breast cancer (TNBC) in the neoadjuvant setting.
| Trial, Design | Population, PD-L1 Status (Assay) | Treatment Arms (n per arm) | pcR Rates | Biomarker Analysis | |
|---|---|---|---|---|---|
| % (95% CI) | OR (95% CI), p | ||||
| GeparNuevo [80], Phase II R |
TNBC Any PD-L1 (on both IC and TC, by Ventana SP163) |
(Window cohort) a → Durvalumab + NabP → Durvalumab + EC (88) | 53.4 (42.5–61.4) Window cohort: 61.0 |
1.45 (0.80–2.63), p = 0.224 Window cohort: 2.22 (1.06–4.64), p = 0.035 |
Trend towards an association between PD-L1 and pCR, not predictive of durvalumab benefit |
| (Window cohort) a → Placebo + NabP → Placebo + EC (86) | 44.2 (33.5–55.3) Window cohort: 41.4 |
||||
| Keynote-173 [83], Phase Ib |
TNBC Any PD-L1 (CPS, by PharmDx 22C3) |
Pembrolizumab + 6 CT regimens b (60) | Overall: 60 (range: 49–71) | NA | Significant association between PD-L1 and pCR |
| Keynote-522 [79], Phase III R |
TNBC Any PD-L1 (CPS, by PharmDx 22C3) |
Pembrolizumab + NabP–Carboplatin → A/E-C + Pembrolizumab (401) | 64.8 (59.9–69.5) | Estimated treatment difference: 13.6% (5.4–21.8, p > 0.001) | Significant association between PD-L1 and pCR, not predictive of pembrolizumab benefit |
| Placebo + NabP–Carboplatin → A/E-C + Placebo (201) | 51.2 (44.1–58.3) | ||||
| Impassion-031 [81,82], Phase III R |
TNBC Any PD-L1 (on IC, by Ventana SP-142) |
Atezolizumab + NabP → Atezolizumab + AC (165) | 58 (50–65) | Rate difference: 17%, (6–27, p = 0.0044) |
Association between PD-L1 and pCR, not predictive of atezolizumab benefit |
| Placebo + NabP → Placebo + AC (168) | 41 (34–49) | ||||
| NeoTRIPaPDL1 [84], phase III R | TNBC Any PD-L1 (on IC, by Ventana SP142) |
Atezolizumab + NabP–Carboplatin (138) | 43.5 (35.1–52.2) | 1.11 (0.69–1.79), p = 0.66 |
Significant association between PD-L1 and pCR (secondary endpoint), not predictive of atezolizumab benefit |
| NabP–Carboplatin (142) | 40.8 (32.7–49.4) | ||||
Abbreviations: R, randomized; pCR, pathologic complete response, OR, odds ratio; TN, triple-negative; R, randomized; IC, immune cells, TC, tumor cells; NabP, nab-paclitaxel; EC, epirubicin–cyclophosphamide; HER2-, HER2-negative; NA, not available; p, paclitaxel; AC, doxorubicin–cyclophosphamide; CPS; combined positive score. a The window phase consisted of 2 weeks of either durvalumab or placebo single agent; it was stopped after 117 patients were recruited. b Six different CT regimens consisting of taxane (with or without carboplatin in various schedules)–anthracyclines+cyclophosphamide.