Abstract SP085: Metastatic TNBC - What’s new on the horizon?

Until very recently, the treatment for locally advanced or metastatic breast cancer revolved solely around sequential chemotherapies, alone or in combination. With the increasing recognition that triple negative breast cancers are a very heterogeneous group of tumors, exciting new strategies have emerged. Here we review some of the recent advances to standard chemotherapy now in clinical use as well discuss new strategies in development. Immunotherapy: There is currently an indication for nab-paclitaxel and atezolizumab for patients with locally advanced or metastatic triple negative breast cancer with PD-L1 positive tumor-infiltrating immune cells. The Impassion130 study first presented a median PFS of 7.2 months with nab-paclitaxel and atezolizumab vs. 5.5 months of nab-paclitaxel and placebo (HR 0.80; 95% confidence interval (CI) 0.69-0.92). Further analyses showed no benefit in the PD-L1 negative group.1 An exploratory overall survival analysis in the PD-L1+ subset showed an increase in the atezolizumab group of 25 months vs 18 in the control group.2 Immunotherapy for metastatic breast cancer will be presented in greater detail in another talk in this session. Sacituzumab govitecan: Sacituzumab govitecan is an antibody-drug conjugate (ADC) targeting Trop-2 and linked with SN-38, the active metabolite of irinotecan and a potent DNA- damaging agent. Trop-2 has been estimated to be expressed in up to 90% of TNBC, making it an attractive target for an ADC. Sacituzumab govitecan was conditionally approved for use after the Phase I/II trial demonstrated and objective response rate of 33.3% and a median overall survival of 13.0 months.3 The recently presented phase III ASCENT trial evaluated patients with metastatic TNBC who had at least 2 previous lines of therapy in the metastatic setting. There was an improvement in median PFS from 1.7 to 5.6 months for patients who received sacituzumab vs. physician’s choice of therapy. The HR for PFS was 0.41; 95% CI: 0.32-0.52) Additionally, there was an improvement in median OS of 6.7 to 12.1 months (HR 0.48; 95%CI:0.38-0.59).4PARP Inhibitors: There are now 2 PARP inhibitors that have FDA approval for use for patients with metastatic breast cancer and a germline BRCA pathogenic variant.5,6 Both Olaparib and Talazoparib demonstrated improvements in PFS which led to FDA approval. While neither the OlympiAD (olaparib) nor the EMBRACA (talazoparib) trial showed statistically significant improvement in OS, both trials showed a significant improvement in quality of life measures. Future Directions: Ongoing trials evaluating further ADCs, targeted therapies and drugs targeting DNA Damage Repair pathways for both germline and somatic pathogenic variants will be discussed 1.Schmid P, Adams S, Rugo HS, et al: Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. NEJM 379:2108-2121, 20182.Schmid P, Rugo HS, Adams S, et al: Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer The Lancet Oncology 21:44-59, 20203.Bardia A, Mayer IA, Diamond JR, et al: Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol 35:2141-2148, 20174.Bardia A, Tolaney S, Loirat D, et al: ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). Annals of Oncology 31:S1142-S1215. 10.1016/annonc/annonc325, 20205.Robson M, Im S-A, Senkus E, et al: Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. NEJM 377:523-533, 20176.Litton JK, Rugo HS, Ettl J, et al: Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. NEJM 379:753-763, 2018 Citation Format: J Litton. Metastatic TNBC - What’s new on the horizon? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP085.