Table 2.
Clinical trials utilizing immune checkpoint inhibitors for the treatment of breast cancer.
| Trial | Inhibitor | Therapeutic strategy | No. pts. | ORR | Median time to response (Range) | Median DoR (months) | Toxicities |
|---|---|---|---|---|---|---|---|
| KEYNOTE-012 Phase I [124] |
Pembrolizumab | Single agent in advanced PD-L1+ TNBC | 32 | 18.5% | 17.9 weeks (7.3 to 32.4 weeks) | Common: arthralgia, fatigue, myalgia, Nausea 15.6% ≥grade 3 toxicity |
|
| KEYNOTE-028 Phase I [126] |
Pembrolizumab | Single agent in ER+, HER2−, locally advanced or metastatic disease, ECOG 0–1, and failure or inability to receive standard therapy | 25 | 12% (95% CI, 2.5–31.2) | 8 weeks (8.7 to >44 weeks) | Common: nausea, fatigue, arthralgia, anorexia, mucositis, pruritus, rash, blurred vision 16% ≥grade 3 toxicity |
|
| KEYNOTE-086 Phase II [125] |
Pembrolizumab | Single agent in advanced PD-L1+ triple negative breast cancer | 170 | 5% regardless of PD-L1 expression | – | – | 12% ≥grade 3 toxicity |
| KEYNOTE-173 Phase Ib [209] |
Pembrolizumab | Neoadjuvant with chemotherapy for locally advanced TNBC (Cohort A: nab-paclitaxel followed by doxorubicin and cyclophosphamide Cohort B: nab-paclitaxel and carboplatin followed by doxorubicin and cyclophosphamide) |
Cohort A: 10 Cohort B: 10 |
Cohort A: 80%, prior to surgery Cohort B: 100%, prior to surgery |
– | – | Myelosuppression: Cohort A: 3/10 Cohort B: 4/10 Cohort A: 80% ≥grade 3 toxicity Cohort B: 100% ≥grade 3 toxicity |
| I-SPY 2 Phase 2 [130] |
Pembrolizumab | Invasive breast cancer with neoadjuvant 12 weeks of paclitaxel with or without pembrolizumab followed by 4 cycles of doxorubicin and cyclophosphamide | 69 | HR+/HER−: 7/25 (28.0%) compared to 13/88 (14.8%) controls TNBC: 15/21 (71.4%) compared to 16/83 (19.3%) controls |
– | – | – |
| JAVELIN Phase Ib [129] |
Avelumab | Metastatic breast cancer refractory to therapy or with progression after standard-of-care therapy | 168 | 3.0% (overall) 5.2% (TNBC) |
– | – | 13.7% ≥grade 3 toxicity |
|
NCT01375842 Phase Ia [131] |
Atezolizumab | TNBC | 63 | 10% (95% CI, 5–17%) | – | – | – |
| IMpassion130 Phase Ib [127] |
Atezolizumab | Combination with nab-paclitaxel in metastatic TNBC treated with ≤3 prior lines of therapy | 32 | 42% (95% CI, 22–63%) | 21 (3 to 26+) | Common: neutropenia |