Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review

Abstract

BackgroundMetastatic triple-negative breast cancer (mTNBC), an aggressive histological subtype, has poor prognosis. Chemotherapy remains standard of care for mTNBC, although no agent has been specifically approved for this breast cancer subtype. Instead, chemotherapies approved for metastatic breast cancer (MBC) are used for mTNBC (National Comprehensive Cancer Network Guidelines [NCCN] v1.2019). Atezolizumab in combination with nab-paclitaxel was recently approved for programmed death-ligand 1 (PD-L1)–positive locally advanced or metastatic TNBC. Published historical data were reviewed to characterize the efficacy of NCCN-recommended (v1.2016) agents as first-line (1L) and second-line or later (2L+) treatment for patients with locally recurrent inoperable or metastatic TNBC (collectively termed mTNBC herein).MethodsA systematic literature review was performed, examining clinical efficacy of therapies for mTNBC based on NCCN v1.2016 guideline recommendations. Data from 13 studies, either published retrospective mTNBC subgroup analyses based on phase III trials in MBC or phase II trials in mTNBC, were included.ResultsA meta-analysis of mTNBC subgroups from three phase III trials in 1L MBC reported pooled objective response rate (ORR) of 23%, median overall survival (OS) of 17.5 months, and median progression-free survival (PFS) of 5.4 months with single-agent chemotherapy. In two subgroup analyses from a phase III study and a phase II trial (n = 40 each), median duration of response (DOR) to 1L chemotherapy for mTNBC was 4.4–6.6 months; therefore, responses were not durable. A meta-analysis of seven cohorts showed the pooled ORR for 2L+ chemotherapy was 11% (95% CI, 9–14%). Median DOR to 2L+ chemotherapy in mTNBC was also limited (4.2–5.9 months) per two subgroup analyses from a phase III study. No combination chemotherapy regimens recommended by NCCN v1.2016 for treatment of MBC showed superior OS to single agents.ConclusionsChemotherapies have limited effectiveness and are associated with unfavorable toxicity profiles, highlighting a considerable unmet medical need for improved therapeutic options in mTNBC. In addition to the recently approved combination of atezolizumab and nab-paclitaxel for PD-L1–positive mTNBC, new treatments resulting in durable clinical responses, prolonged survival, and manageable safety profile would greatly benefit patients with mTNBC.

Eribulin Plus Pembrolizumab in Patients with Metastatic Triple-Negative Breast Cancer (ENHANCE 1): A Phase Ib/II Study

“…Triple-negative breast cancer (TNBC) is characterized by aggressive clinicopathologic features (eg, larger tumor size, higher grade tumors) (1), a poorer prognosis, earlier recurrence, and high death rates (1,2). While some combination therapies have recently shown promise in the first-line (1L) setting for metastatic TNBC (mTNBC), limited data are available for second-line and later (2L+) therapeutics.…”

“…While some combination therapies have recently shown promise in the first-line (1L) setting for metastatic TNBC (mTNBC), limited data are available for second-line and later (2L+) therapeutics. The median overall survival (OS) for patients with mTNBC treated in the 2L+ is 8 to 15 months (2). There is, therefore, an unmet clinical need to identify new and more effective treatments for improving the prognosis of patients with mTNBC, especially in the later-line setting.…”

Single-cell long noncoding RNA (lncRNA) transcriptome implicates MALAT1 in triple-negative breast cancer (TNBC) resistance to neoadjuvant chemotherapy

“…Neoadjuvant chemotherapy (NAC) remains the gold standard form of therapy for TNBC patients, with limited effectiveness, narrower durations of response, and considerably toxic profiles 2 . As a highly heterogeneous BC subtype, there are very few options for treating TNBC patients that confer resistance to conventional chemotherapy 3 .…”

SOX4 promotes the growth and metastasis of breast cancer

“…The cause of death by breast cancer is often not due to the primary tumor, but due to the metastasis of cancer cells to other tissues and organs. Distant metastasis usually causes the failure of clinical therapy [4]. Therefore, deep understanding of the mechanism underlying metastasis would be crucial to identify novel therapeutic targets and for the treatment of breast cancer.…”