Sacituzumab Govitecan Elicits Durable Responses for Pretreated TNBC

Article

Treatment with sacituzumab govitecan was well-tolerated and induced durable responses, some lasting longer than 1 year, for heavily pretreated patients with metastatic triple-negative breast cancer.

Linda T. Vahdat, MD

Treatment with sacituzumab govitecan (IMMU-132) was well-tolerated and induced durable responses, some lasting longer than 1 year, for heavily pretreated patients with metastatic triple-negative breast cancer (TNBC), according to findings from an ongoing phase I/II study presented at the 2016 San Antonio Breast Cancer Symposium (SABCS).

In the single-arm trial, the confirmed objective response rate (ORR) was 30% with sacituzumab govitecan, and the duration of response was 8.9 months (95% CI, 6.1-11.3). The median progression-free survival was 6.0 months (95% CI, 5.0-7.3) and the median overall survival was 16.6 months (95% CI, 11.1-20.6).

"The findings are truly outstanding," said senior study author Linda T. Vahdat, MD, MBA, from Weill Cornell Medicine and NewYork-Presbyterian Hospital. "The confirmed response rate is near 30%, and what's really striking is that this is a group of patients with a median of 5 prior regimens for breast cancer—it is a very heavily pretreated population."

Sacituzumab govitecan is an antibody-drug conjugate that consists of the active metabolite of irinotecan, SN-38, linked with a humanized IgG antibody targeted against TROP-2, a cell-surface glycoprotein that is expressed in more than 90% of TNBC. In the study, 89% of assessable patients (n = 46) had moderate (2+) to strong (3+) TROP-2 expression. In most cases, this expression was seen in ≥50% of tumor cells.

The ongoing study enrolled 69 patients with relapsed/refractory metastatic TNBC. The median age of patients was 56 years (range, 31-81). Sacituzumab govitecan was administered at 10 mg/kg on days 1 and 8 of each 28-day cycle. A median of 14 doses were administered (range, 1-67) over a median treatment duration of 5.3 months (range, 0.2-23.1).

Patients had an ECOG performance status of 0 (33%) and 1 (67%) and the primary stage at initial diagnosis was I to II (55%), III (30%), and IV (14%). Patients had received a median of 5 prior therapies (range, 1-12), most commonly taxanes (97%), cyclophosphamide (91%), anthracyclines (84%), and platinum agents (70%). The most common sites of disease at study entry were the lymph nodes (62%), lung (51%), liver (43%), chest (41%), and bone (30%).

The complete response (CR) rate with sacituzumab govitecan was 3% and the partial response (PR) rate was 28%. Additionally, 45% of patients had stable disease (SD), with 16% of the responses lasting for ≥6 months. The clinical benefit rate (CR + PR + SD ≥6 months) was 46%.

After a median follow-up of 16.6 months, 7 patients continued to receive therapy, with 6 continuing to respond at the time of the analysis. There were 3 durable responses that lasted 13 to 21 months.

"These aren't just flash in the pan type of responses, they are actually quite durable," said Vahdat. "When you have a drug that you can keep someone on in triple-negative breast cancer for almost a year you get excited, because the median survival in TNBC is a little under a year."

The most common grade ≥3 adverse events (AEs) were neutropenia (39%), with febrile neutropenia occurring in 7% of patients. Dose reductions were required for 19% of patients in the first 2 cycles, primarily related to neutropenia. Further reductions were needed for 16% of patients in later cycles of treatment. There were 3 discontinuations related to AEs (grade 3 rash/mucositis; grade 3 transient infusion reaction; grade 2 fatigue).

The most common all-grade AEs were nausea (74%), neutropenia (68%), diarrhea (59%), anemia (55%), vomiting (51%), fatigue (51%), alopecia (45%), constipation (38%), rash (28%), abdominal pain (26%), and leukopenia (25%). The most common grade ≥3 AEs, regardless of cause, were neutropenia (39%), leukopenia (16%), anemia (14%), diarrhea (13%), vomiting (10%), and hypophosphatemia (10%).

"The drug is very well tolerated, neutropenia is about 39% for grade 3/4 and there's very little diarrhea," said Vahdat. "I think the worst side effect is that patients get alopecia."

Data from the ongoing phase I/II study will be submitted to the FDA for a potential accelerated approval, according to the poster presented at SABCS. This submission would be completed under a breakthrough therapy designation received in February 2016 for the medication in TNBC following at least 2 treatments for metastatic disease. A phase III study is currently being planned under a special protocol agreement with the FDA.

Bardia A, Diamond JR, Mayer IA, et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate (ADC) for the treatment of relapsed/refractory, metastatic triple-negative breast cancer (mTNBC): Updated results. Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract P4-22-15.

<<<

View more from the 2016 San Antonio Breast Cancer Symposium

Overall, 70% of patients treated with sacituzumab govitecan had some reduction in tumor size from baseline. There were 23 patients with tumor reduction of ≥30% (2 confirmed CRs, 19 confirmed PRs, and 2 unconfirmed PRs).

Related Videos
Christian Marth, MD, PhD, head, professor, Department of Obstetrics and Gynecology, Innsbruck Medical University
Mansoor Raza Mirza, MD, chief oncologist, Department of Oncology, Rigshospitalet, Copenhagen University Hospital
Vijayakrishna Gadi, MD, PhD, and Megan Kruse, MD
Judy Hayek, MD, gynecologic oncology fellow, State University of New York (SUNY) Downstate College of Medicine
Leslie M. Randall, MD, MAS, professor, division head, Department of Obstetrics and Gynecology – Gynecologic Oncology, Virginia Commonwealth University School of Medicine Obstetrics and Gynecology
Dimitrios Nasioudis, MD, fellow, Gynecologic Oncology, Perelman School of Medicine, the University of Pennsylvania
Sara Corvigno, MD, PhD, translational researcher, oncology, The University of Texas MD Anderson Cancer Center
I-Chia (Daniel) Liu, MD
Robert W. Mutter, MD