Recently approved targeted therapies to treat patients with advanced or metastatic TNBC (PARP inhibitors, immune checkpoint inhibitors, and antibody-drug conjugate)

Therapeutic targetTreatment class Drug/combinationRCT (phase 3) identifierTherapeutic considerationsAuthor, year, reference
ADP ribose polymerase PARP 1PARP1 inhibitor olaparibOlympiAD NCT02000622In the OlympiAD study, olaparib has improved PFS compared with CHT of physician's choice, among pts with a gBRCA1/2 mutation & HER2-negative metastatic BCRobson et al. 2019 [29]
ADP ribose polymerase PARPPARP inhibitor talazoparibEMBRACA NCT01945775In the EMBRACA trial, talazoparib prolonged PFS vs. CHT & improved PRO in gBRCA1/2-mutated ABCLitton et al. 2020 [30]
PD-L1Anti-PD-L1 monoclonal antibody atezolizumab + nab-paclitaxel (CHT)IMpassion130 NCT02425891In the 2nd interim OS analysis of the IMpassion130 trial, no significant difference in OS between the treatment groups in the ITT population was reported, but a clinically meaningful OS benefit with atezolizumab + nab-paclitaxel in pts with PD-L1 immune cell-positive disease was noted. In pts with PD-L1 immune cell-positive metastatic TNBC, atezolizumab + nab-paclitaxel is a valid therapeutic optionSchmid et al. 2020 [31]
PD-1Anti-PD-1 monoclonal antibody pembrolizumab + CHTKEYNOTE-355 NCT02819518Pembrolizumab-CHT revealed a clinically meaning- ful improvement in PFS vs. placebo-CHT, in pts with metastatic TNBC (CPS ≥ 10); such results suggest that the addition of pembrolizumab to standard CHT for the 1-st-line treatment of metastatic TNBC is beneficialCortes et al. 2020 [32]
The human (Trop-2)Antibody-drug conjugate sacituzumab govitecan-hziy [a combination of a monoclonal antibody, targeting Trop-2 with SN-38 (a cytotoxic, potent topoisomerase I inhibitor; a metabolite of irinotecan, conjugated to the antibody by a cleavable linker)]IMMU-132-01 NCT01631552Sacituzumab govitecan-hziy was associated with durable objective responses in pts with heavily pretreated metastatic TNBCBardia et al. 2019 [33]

ABC: advanced breast cancer; CPS: combined positive score; g: germline; ITT: intention-to-treat; PFS: progression-free survival; pts: patients; PRO: patient-reported outcomes; RCT: randomized controlled trial