Summary of clinical trials testing immune checkpoint inhibitors in early breast cancer (EBC), for which preliminary or final results have been presented and/or published
| Trial | Design | Setting | Population (n) | Drugs (n per arm) | pCR rates % (95% CI) | OR (95% CI), P | Biomarker analysis | Ref. |
|---|---|---|---|---|---|---|---|---|
| GeparNuevo | II Randomized | Neoadjuvant | TN (174)Any PD-L1 | Durvalumab (2w) | 53.4 (42.5–61.4) Window cohort: 61.0 | 1.45 (0.80–2.63), P = 0.224 | sTILs and PD-L1 (trend) associated with pCR, not predictive for Durvalumab benefit | [14] |
| Durvalumab (2w) | 44.2 (33.5–55.3) Window cohort: 41.4 | Window cohort: 2.22 (1.06–4.64), P = 0.035 | iTILs (increase between baseline and end of the window phase) predictive for Durvalumab benefit (OR 9.36, 95% CI 1.26–69.65, P = 0.029) | |||||
| KEYNOTE-173 | Ib | Neoadjuvant | TN (60) Any PD-L1 | Pembrolizumab + 6 CT regimens (cohort A-F) | Overall: 60 (range: 49–71) | NA | sTILs and PD-L1 associated with pCR | [16] |
| KEYNOTE-522 | III | Neoadjuvant | TN (602) Any PD-L1 | 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) | PD-L1 associated with pCR, not predictive for Pembrolizumab benefit | [17] |
| Placebo + NabP-carboplatin → A/E-C + placebo (201) | 51.2 (44.1–58.3) | |||||||
| NeoTRIPaPDL1 | III | Neoadjuvant | TN (280) Any PD-L1 | Atezolizumab + NabP-carboplatin (138) | 43.5 (35.1–52.2) | 1.11 (0.69–1.79), P = 0.66 | PD-L1 associated with pCR, not predictive for Atezolizumab benefit | [19] |
| NabP-carboplatin (142) | 40.8 (32.7–49.4) | |||||||
| IMpassion031 | III | Neoadjuvant | TN (333) Any PD-L1 | Placebo + NabP → placebo + A (168) | 41.1 | Delta pCR 16.5 (5.9– 27.1), P = 0.0044 | PD-L1 associated with pCR, not predictive for Atezolizumab benefit | [18] |
| Atezolizumab + NabP → atezolizumab + A (165) | 57.6 | |||||||
| I-SPY 2 | II Adaptive-randomized | Neoadjuvant | HER2- (205) Any PD-L1 | Pembrolizumab + paclitaxel → AC (69) | Total: 44 (33–55) | Probability superior to control: Total: > 99.9%TN: > 99.9%HR+: 99.6% | NA | [15] |
| Paclitaxel → AC (181) | Total: 17 (11–23) | |||||||
| GIADA | II | Neoadjuvant | Luminal-B (43) Any PD-L1 | EC → Nivolumab + triptorelin + exemestane | 16.3 (7.4–34.9) | TILs and specific immune infiltrate characteristics at baseline associated with pCR; anthracycline-induced increase in cytotoxic T-cells and decrease in T-regulatory T cells | [41] |
window phase stopped after 117 patients recruited (ethical concerns);
CT regimens; cohort A: NabP → doxorubicin-cyclophosphamide (AC); cohort B: NabP-Carboplatin AUC6 → AC; cohort C: NabP-Carboplatin AUC5 → AC; cohort D: NabP-Carboplatin AUC2 → AC; cohort E: Paclitaxel-Carboplatin AUC5 → AC; cohort F: Paclitaxel-Carboplatin AUC2 → AC;
pCR was a secondary endpoint;
one-sided significance boundary P = 0.0184;
estimated rates of pCR;
2-step statistical design: second step (8 pCR/43 patients) not met;
w: weeks; NA: not available; pCR: pathologic complete response; OR: odds ratio; EC: epirubicin-cyclophosphamide; sTILs: stromal TILs; iTILs: intra-tumoral TILs; AC: doxorubicin-cyclophosphamide