Table 6 Selected phase III clinical trials assessing immune checkpoint inhibitors in the metastatic, neoadjuvant and adjuvant settings of triple negative breast cancer
Trial | Target | Treatment vs. control arm | Phase | Setting | Key results (Treatment vs. control) |
|---|---|---|---|---|---|
Targeting the immune microenvironment – Metastatic setting | |||||
PDL1 inhibition (atezolizumab) | Atezolizumab +  nab-paclitaxel vs Placebo +  nab-paclitaxel | III | Previously untreated TNBC | ITT population PFS 7.2 vs. 5.5 months HR 0.80 (95% CI 0.69- 0.92; P = 0.002) PDL1-positive population PFS 7.5 vs. 5 months HR 0.62 (95%CI 0.49–0.78; P < 0.001) | |
KEYNOTE-355 [12] | PD1 inhibition (pembrolizumab) | Pembrolizumab  + chemotherapy (investigator’s choice) vs Placebo + chemotherapy (investigator’s choice) | III | Previously untreated TNBC | Combined positive score ≥ 10 population PFS 9.7 vs 5.6 months HR 0.65 (95%CI 0.49–0.86; P = 0.001) |
Targeting the immune microenvironment – Neoadjuvant setting | |||||
PD1 inhibition (pembrolizumab) | Chemotherapy + pembrolizumab surgery pembrolizumab vs Chemotherapy + placebo surgery placebo | III | TNBC | ITT population pCR 63% vs. 55.6% PDL1-positive population pCR 68.9% vs. 54.9% PDL1-negative population pCR 45.3% vs. 30.3% Lymph node negative 64.8% vs. 44.1% Lymph node negative 64.9% vs 58.6% Event free survival at 36 months 84.5% vs. 76.8% HR 0.63 (95%CI 0.48–0.82; P < 0.001) | |
IMpassion031 [171] | PDL1 inhibition (atezolizumab) | Chemotherapy + atezolizumab surgery atezolizumab vs Chemotherapy + placebo surgery monitoring | III | TNBC | ITT population pCR 58% vs. 41% PDL1-positive population pCR 69% vs. 49% |
NeoTRIPaPDL1 [174] | PDL1 inhibition (atezolizumab) | Chemotherapy + atezolizumab surgery chemotherapy vs Chemotherapy surgery chemotherapy | III | TNBC | ITT population pCR 43.5% vs. 40.8% PDL1-positive population pCR 51.9% vs 48% Event free survival primary endpoint results—pending |
Targeting the immune microenvironment – Adjuvant setting | |||||
ALEXANDRA/ IMpassion030 (NCT03498716) | PDL1 inhibition (atezolizumab) | Chemotherapy + atezolizumab vs Chemotherapy alone | III | TNBC | Ongoing Primary endpoint is iDFS Secondary endpoints include iDFS by PDL1 status, lymph node status and OS |
SWOG S1418 (NCT02954874) | PD1 inhibition (pembrolizumab) | Pembrolizumab vs Observation | III | TNBC with residual disease measuring at least 1Â cm in the breast and/or lymph node | Ongoing Primary endpoint is iDFS Secondary endpoints include OS and DFS |
A-BRAVE (NCT02926196) | PDL1 inhibition (avelumab) | Avelumab vs Observation | III | TNBC | Ongoing Stratum A: surgery of the primary tumor followed by adjuvant chemotherapy Stratum B: residual disease after surgery of the primary tumor Primary endpoint is DFS Secondary endpoints include OS |