Copyright
©The Author(s) 2021.
World J Clin Oncol. Mar 24, 2021; 12(3): 164-182
Published online Mar 24, 2021. doi: 10.5306/wjco.v12.i3.164
Published online Mar 24, 2021. doi: 10.5306/wjco.v12.i3.164
Table 1 Historical outcomes in metastatic triple negative breast cancer
ORR (%) | PFS (mo) | OS (mo) | |
Single agent chemotherapy | |||
1L | 10.0-28.0 | 3.5-5.4 | 9.9-17.5 |
2L | 6.0-18.0 | 2.7-3.4 | 9.2-15.2 |
Combination chemotherapy | |||
1L | 14.8-64.3 | 4.8-9.0 | 13.9-24.2 |
2L+ | 27.01-60.0 | 2.9-7.0 | 8.1-16.5 |
Table 2 Immunotherapy as a monotherapy in metastatic triple negative breast cancer
Trial | n | Drug | ORR 1st line | ORR ≥ 1 prior line | Median OS (mo) 1st line | Median OS (mo) ≥ 1 line | Ref. |
NCT01375842 Phase Ia | 116 | Atezolizumab | 24% | 6% | 17.6 | 7.3 | Emens et al[52], 2019 |
KEYNOTE-012 Phase Ib | 32 | Pembrolizumab | 18.5 | 11.2 | Nanda et al[50], 2016 | ||
JAVELIN/Phase Ib | 58 | Avelumab | 5.2 | 9.2 | Dirix et al[51], 2018 | ||
KEYNOTE-086 Phase II | 170 | Pembrolizumab | 23.1% | 5.3 | 18.0 | 9.0 | Adams et al[53], 2019 |
KEYNOTE-119/Phase III | 622 | Pembrolizumab vs chemo | 9.6 vs 10.6 | CPS ≥ 1; 10.7 vs 10.2. CPS ≥10; 12.7 vs 11.6. CPS ≥ 20; 14.9 vs 12 | Verret et al[83], 2019 |
Table 3 Early studies of Immunotherapy and chemotherapy in metastatic triple negative breast cancer
Trial | n | Drug | ORR 1st line | ORR ≥ 2 line | mOS 1st line | mOS 2nd line | Ref. |
NCT01633970 Phase Ib | 33 | Atezolizumab + nab-paclitaxel | 53.8% | 30 | 24.2 | 12.4 | Adams et al[55], 2019 |
KEYNOTE-150 Phase 1b/II | 82 | Pembrolizumab + Eribulin | 25% | 26.5 | 17.7 | NE | Tolaney et al[57], 2018 |
Pilot and phase II. 1-2L1 | 29 | Pembrolizumab + capecitabine or paclitaxel | 43% pembro + cap. 23% pembro + paclitaxel | 13.8 pembro + cap 7.9 pembro + pac | Page et al[90], 2019 |
Table 4 Phase III first line metastatic immunotherapy + chemotherapy
IMpassion130 (PD-L1 inhibitor) | Keynote-355 (PD1 inhibitor) | IMpassion131 (PD-L1 inhibitor) | |
Drugs | Atezolizumab/nab-paclitaxel vs placebo/nab-paclitaxel | Pembrolizumab + chemotherapy (nab-paclitaxel or paclitaxel or gemcitabine/carboplatin vs placebo + chemo | Atezolizumab/paclitaxel vs placebo/paclitaxel |
ITT (N) | 451 vs 451 (1:1 randomisation) | 566 vs 281 (2:1 randomisation) | 430 vs 221 (2:1 randomisation) |
Inclusion | ≥ 1 yr DFI | ≥ 6 mo DFI | ≥ 1 yr DFI |
PD-L1 status | IC [positive (≥ 1%) vs negative (< 1%)] | CPS [positive (≥ 1%) vs negative (< 1%)] | IC [positive (≥ 1%) vs negative (< 1%)] |
SP142 antibody ventana platform | PD-L1 IHC 22C3 pharmDx kit | SP142 antibody ventana platform | |
Primary endpoints | PFS and OS in ITT population | PFS and OS by PD-L1 status (CPS ≥ 10 and ≥ 1) in ITT | PFS and OS in PD-L1 positive cohort |
Median FU | 18.0 mo (ASCO 2019) | 25.9 mo and 26.3 mo (ASCO 2020) | 8.6 and 9 mo (ESMO 2020) |
PFS in PD-L1 + | 7.5 mo vs 5 mo | 9.6 mo vs 5.6 mo | 5.7 mo vs 5.6 mo |
OS in PD-L1 + | 25.4 mo vs 17.9 mo | Awaited | 22.1 mo vs 28.3 mo |
Table 5 Pivotal Phase III studies of poly adenosine diphosphate ribose polymerase inhibitors in patients with germline BRCA1/BRCA2 mutations
Table 6 Key phase I/II/III involving antibody drug conjugates and targeted therapies
Trial | n | Drug | ORR 1st line | ORR ≥ 2 line | mPFS ≥ 2 line | mOS 1st line | mOS ≥ 2 line | Ref. |
NCT01631552 phase II | 108 | Sacituzumab govitecan | 33% | 5.5 | 12.4 | Schmid et al[61], 2020 | ||
NCT03310957 phase I/II | 51 | Pembrolizumab + ladiratuzumab vedoitin | 54% | - | Han et al[78], 2020 | |||
NCT029380341 phase Ib/II | 21 | US-1402 | 33% | - | Kim et al[82], 2019 | |||
NCT03279257 phase 1b/II | 40 | Alpelisib | 57% | 7 | Sharma et al[84], 2018 | |||
LOTUS phase II | 124 | Ipatasertib | 40% | 6.2 | Kim et al[86], 2017 | |||
NCT02978716 phase II | 102 | Trilaciclib | 43% | 20.6/17.6 | Tan et al[88], 2019 | |||
ASCENT phase III | 529 | Sacituzumab Govitecan | 35% | 5.6 | 12.1 | Bardia et al[77], 2020 |
- Citation: O'Reilly D, Sendi MA, Kelly CM. Overview of recent advances in metastatic triple negative breast cancer. World J Clin Oncol 2021; 12(3): 164-182
- URL: https://www.wjgnet.com/2218-4333/full/v12/i3/164.htm
- DOI: https://dx.doi.org/10.5306/wjco.v12.i3.164