Background
How to enrich the TNBC population: PD-L1 and emerging biomarkers
PD-L1 expression
Setting | Trial | Phase | Regimen | Patients | Status |
---|---|---|---|---|---|
Neoadjuvant | NCT03639948 (NeoPACT) | II | Carboplatin + docetaxel + pembrolizumab | 100 | R |
NCT03289819 | II | Pembrolizumab + Nab-paclitaxel ➔ pembrolizumab + epirubicin and cyclophosphamide | 50 | R | |
NCT03356860 (B-IMMUNE) | II | Paclitaxel + epirubicin + cyclophosphamide ± durvalumab | 57 | R | |
NCT02685059 (GeparNuevo) | II | Epirubicin + nab-paclitaxel + cyclophosphamide ± durvalumab | 174 | ANR | |
Neoadjuvant/Adjuvant | NCT03036488 (KEYNOTE-522) | III | Carboplatin + paclitaxel + (anthracycline) + cyclophosphamide ± pembrolizumab➔ pembrolizumab | 1174 | ANR |
NCT03281954 | III | Doxorubicin + cyclophosphamide + paclitaxel + carboplatin ± atezolizumab ➔ atezolizumab | 1520 | R | |
NCT03197935 (IMpassion031) | III | Doxorubicin + cyclophosphamide + nab-paclitaxel ± atezolizumab ➔ atezolizumab | 204 | ANR | |
Adjuvant only for patients with residual disease after neoadjuvant chemotherapy | NCT02954874 | III | Pembrolizumab vs. observation | 1000 | R |
NCT03756298 | II | Capecitabine ± atezolizumab | 284 | R | |
Adjuvant | NCT03498716 (IMpassion030) | III | Paclitaxel ➔ dose-dense doxorubicin/epirubicin + cyclophosphamide ± atezolizumab | 2300 | R |
NCT02926196 (A-Brave) | III | Avelumab vs. observation | 335 | R | |
Locally advanced or metastatic TNBC | NCT02768701 | II | Cyclophosphamide + pembrolizumab | 40 | ANR |
NCT03121352 | II | Carboplatin, nab-paclitaxel and pembrolizumab | 30 | R | |
NCT02819518 (KEYNOTE-355) | III | Abraxane or paclitaxel or carboplatin/gemcitabine ± pembrolizumab | 858 | ANR | |
NCT02555657 (KEYNOTE-119) | III | Capecitabine, eribulin, gemcitabine, or vinorelbine as TPC vs. pembrolizumab | 600 | ANR | |
NCT03644589 | II | Cisplatin + pembrolizumab | 60 | NYR | |
NCT02755272 | II | Carboplatin + gemcitabine ± pembrolizumab | 87 | R | |
NCT02447003 (KEYNOTE-086) | II | Pembrolizumab monotherapy | 285 | ANR | |
NCT03125902 (IMpassion131) | III | Paclitaxel ± atezolizumab | 540 | R | |
NCT03164993 (ALICE) | II | Pegylated liposomal doxorubicin + cyclophosphamide ± atezolizumab | 75 | R | |
NCT03206203 | II | Carboplatin + gemcitabine | 185 | R | |
NCT03606967 | II | Nab-paclitaxel + durvalumab ± neoantigen vaccine | 70 | NYR | |
NCT03616886 (SYNERGY) | II | Paclitaxel, carboplatin, durvalumab ± oleclumab | 171 | R | |
NCT03371017 (IMpassion132) (early recurrent) | III | Carboplatin + gemcitabine or capecitabine ± atezolizumab | 350 | R | |
NCT03167619 (DORA) | II | Durvalumab + olaparib | 60 | R |
Tumor-infiltrating lymphocytes (TILs)
Gene signatures
Tumor mutational burden (TMB)
MSI and MMR deficiency
Choosing the right chemotherapeutic partner for immunotherapy
Anthracyclines
Taxanes
Cyclophosphamide
Gemcitabine
Single agent versus combination immunotherapy in TNBC
Trial | Setting | Drug | Patients | Results | Ref. |
---|---|---|---|---|---|
Single agent immunotherapy | |||||
KEYNOTE-012 NCT01848834 | Advanced PD-L1+ TNBC | Pembrolizumab 10 mg/kg Q2W | 27 | ORR, 18.5% Median PFS, 1.9 months Median OS, 11.2 months | [60] |
KEYNOTE-086 NCT02447003 | Advanced, untreated, any PD-L1 TNBC (cohort A) Advanced, untreated PD-L1+ TNBC (cohort B) | Pembrolizumab 200 mg Q3W | Cohort A: 170 Cohort B: 84 | ORR Cohort A, 4.7% ORR Cohort B, 22.6% Median PFS Cohort A, 2 months Median PFS Cohort B, 2.1 months Median OS Cohort A, 8.9 months Median OS Cohort B, 19.2 months | |
JAVELIN NCT01772004 | TNBC unselected for PD-L1 (68.8% had PD-L1+ tumors) | Avelumab 10 mg/kg every 2 weeks | 58 | ORR, 5.2% (22.2% in PD-L1+) Median PFS, 1.5 months Median OS, 9.2 months | [62] |
NCT01375842 | Advanced TNBC unselected for PD-L1 (65.7% had PD-L1+ tumors) | Atezolizumab 15 or 20 mg/kg, or at a 1200-mg flat dose, Q3W | 116 | ORR, 10% (12.7% in PD-L1+) Median PFS, 1.4 months by RECIST Median PFS, 1.9 months by irRECIST Median OS, 8.9 months | [63] |
Combination of immunotherapy and chemotherapy | |||||
KEYNOTE-150 NCT02513472 | Advanced TNBC unselected for PD-L1 | Eribulin ± pembrolizumab 200 mg Q3W | 107 | ORR, 26.4% (30.6% in PD-L1+) Median PFS, 4.2 months Median OS, 17.7 months | [59] |
IMpassion130 NCT02425891 | Untreated metastatic TNBC unselected for PD-L1 | Nab-paclitaxel ± atezolizumab 840 mg Q2W | 902 (451 treated with atezolizumab) | ORR, 56% (58.9% in PD-L1+) Median PFS, 7.2 months Median PFS, 7.5 months (PD-L1+) Median OS, 21.3 months Median OS, 25 months (PD-L1+) |