Abstract P2-11-01: Safety and efficacy of sacituzumab govitecan (anti-Trop-2-SN-38 antibody-drug conjugate) as ≥3rd-line therapeutic option for treatment-refractory HER2-negative metastatic breast cancer (HER2Neg mBC)
Authors: Kalinsky K , Isakoff SJ , Tolaney SM , Juric D , Mayer IA , Vahdat LT , Diamond JR , O'Shaughnessy J , Moroose RL , Santin AD , Shah NC , Abramson V , Goldenberg DM , Sharkey RM , Washkowitz SA , Wegener WA , Iannone R , Bardia A 
Published: May 2019

Abstract
Background: Sacituzumab govitecan is an antibody-drug conjugate consisting of SN-38, the active metabolite of irinotecan, conjugated to a humanized mAb targeting Trop-2 (trophoblastic antigen-2), which is highly expressed in many epithelial cancers. A phase I/II basket trial (NCT01631552) investigated its activity in patients (pts) with advanced epithelial cancers. Herein, we summarize pooled safety and efficacy findings in 162 pts with HER2-negative metastatic breast cancer (mBC) accrued between 7/2013 and 6/2017 who received at least 2 prior therapies for metastatic disease and were treated with sacituzumab govitecan at the 10 mg/kg dose level.
Methods: Patients with triple-negative (N=108) and patients with hormone-receptor positive (N=54) mBC received 10 mg/kg sacituzumab govitecan on days 1 & 8 of a 21-day cycle continued until progression or unacceptable toxicity. All pts had measurable disease by CT or MRI. Efficacy was assessed locally by RECIST 1.1 including overall response rate (ORR) and Kaplan-Meier estimates of duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Adverse events (AE) were evaluated according to CTCAE v4.0
Results: The patient cohort (161 female /1 male; median age 55 yrs, range 31-80) received a median of 4 prior therapies for metastatic disease (range 2-17), with prior chemotherapy agents in the metastatic setting including taxane (68%), capecitabine (60%), platinum (59%), gemcitabine (44%), eribulin (41%), and anthracycline (38%). 77 pts have died, with 57 in long-term follow-up and 28 still on treatment at data cutoff. The median number of administered sacituzumab govitecan doses was 14 (range 1-88). Treatment was generally well tolerated. 29% of pts had dose reductions, 3% discontinued treatment due to drug-related AEs, and there were no treatment-related deaths. Based on currently available AE data, grade ≥ 3 toxicity included neutropenia (43%), anemia (9.5%), diarrhea (7.0%) and febrile neutropenia (6.3%). For the TNBC subgroup, with a median follow-up of 9.3 months, the ORR was 33% (3 CRs + 33 PRs /108) with a median DOR of 8.3 months (95% CI: 4.8 – 11.6). For the ER+ subgroup, with a median follow-up of 10.0 months, the ORR was 31% (17 PRs/54) with a median DOR of 7.4 months (95% CI: 4.4 – 18.3). The combined HER2Neg ORR was 33% (3 CRs+50 PRs/162), with a median DOR of 8.3 months (95% CI: 4.9 - 10.8), PFS of 5.6 months (95% CI: 5.1 – 6.9) and OS of 13.0 months (95% CI: 11.5 - 15.0). The ORR was comparable for pts ≤ 50 yrs. old [32.2% (19/59)] vs. &gt; 50 yrs old [33.0% (34/103)] and little different for pts with 2 prior therapies [35.4% (17/48)] vs. &gt;2 prior therapies [31.6% (36/114)].
Conclusions: Monotherapy with sacituzumab govitecan was well tolerated with a manageable safety profile, and achieved a 30+% objective response rate among heavily pre-treated patients with HER2-negative metastatic breast cancer regardless of ER status.
Citation Format: Kalinsky K, Isakoff SJ, Tolaney SM, Juric D, Mayer IA, Vahdat LT, Diamond JR, O'Shaughnessy J, Moroose RL, Santin AD, Shah NC, Abramson V, Goldenberg DM, Sharkey RM, Washkowitz SA, Wegener WA, Iannone R, Bardia A. Safety and efficacy of sacituzumab govitecan (anti-Trop-2-SN-38 antibody-drug conjugate) as ≥3rd-line therapeutic option for treatment-refractory HER2-negative metastatic breast cancer (HER2Neg mBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-11-01.