Michele Simmons, PharmD
SECU Cancer Center of Mission Health
The 2017 San Antonio Breast Cancer Symposium was held December 5–9, 2017, in San Antonio, TX. The 40th-anniversary symposium began in true Texas-style with an all-female mariachi band performing in the lobby prior to the opening reception on December 5. The first night’s events focused on recognition of the individuals responsible for transforming the 1-day annual symposium with 141 attendees from five states—formed to reduce the breast cancer death rate in San Antonio and surrounding counties—to the 5-day international scientific symposium with more than 7,000 attendees from over 90 countries that it has become. The following summary presents highlights from the symposium.
Richard Pazdur, MD, in the award lecture “Past and Future of Cancer Drug Development,” introduced the concept of a dynamic regulatory environment at the U.S. Food and Drug Administration (FDA) in which society’s demands and scientific advances are considered. In an era in which half of the breakthrough approvals are occurring in oncology, Pazdur highlighted the need for committed people to take calculated risks to ensure that the health of the American public is protected. With his review of the last 40 years of moving from extremely toxic chemotherapy with manageable toxicities to checkpoint inhibition, he challenged all to ponder what oncology will look like in 40 years.
Richard Gray, MSc, from the University of Oxford, presented findings of the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) regarding dose-intense chemotherapy regimens. Data from meta-analysis indicate that shortening the interval between treatment cycles of anthracycline- and taxane-based chemotherapy reduces breast cancer recurrence and breast cancer mortality. Specifically, a comparison of dose-intense therapy received every 2 weeks versus every 3 weeks showed that the patients on the 2-weekly regimen had statistically significant reductions in breast cancer recurrence rate (24% vs. 28.3%) and 10-year breast cancer mortality rate (16.8% vs. 19.6%). The benefits were seen in both estrogen receptor (ER)–negative and ER-positive breast cancers. Although no increases in mortality without recurrence were seen in patients who received dose-intense treatment, more studies in toxicities are needed.
Aditya Bardia, MD, from Massachusetts General Hospital, presented data from a phase 2 trial using sacituzumab govitecan—an antibody anti-TROP-2 drug conjugate—for patients with relapsed, refractory metastatic triple negative breast cancer (mTNBC). Sacituzumab govitecan consists of the active metabolite of irinotecan, SN-38, and a humanized IgG antibody targeted against TROP-2, which is expressed on the cell surface of more than 90% of TNBC. Because of the medication’s ability to address an unmet need, the FDA granted a breakthrough therapy designation to sacituzumab govitecan as a treatment for mTNBC after at least two treatments. The study of 110 patients with a median age of 55 tested sacituzumab govitecan at 10 mg/kg on days 1 and 8 of a 28-day cycle. An objective responsive rate (ORR) of 34% was achieved in the heavily pretreated patients. With a median time to response of 2 months and a median overall survival of 12.7 months, Bardia concluded that sacituzumab govitecan demonstrated significant clinical activity as third-line or greater treatment in patients with relapsed, refractory mTNBC. Common adverse events were neutropenia (63%), nausea (63%), diarrhea (56%), anemia (52%), fatigue (50%), and vomiting (46%). ASCENT is the phase 3 randomized study versus physician treatment of choice currently enrolling to confirm the use of sacituzumab govitecan in mTNBC.
On two evenings, clinical investigators presented cases from the community, providing their perspectives on emerging research and actual patients with breast cancer. The panel of medical oncologists reviewed various treatment regimens for patient scenarios posed by community oncologists via satellite. The first set of presentations focused completely on the emerging role of poly ADP ribose polymerase (PARP) inhibitors in the management of breast cancer. This discussion paved the way for a later presentation on the benefit of talazoparib—a novel PARP inhibitor.
Jennifer Litton, MD, presented data from EMBRACA—a phase 3 trial comparing talazoparib to physician’s treatment of choice in patients with advanced BRCA-mutation breast cancer. Talazoparib works dually by inhibiting the PARP enzyme and trapping PARP on DNA to prevent DNA damage repair and lead to death in BRCA-mutated cells. Patients treated with talazoparib (1 mg daily) had significantly prolonged progression-free survival compared with those who received treatment of choice (median of 8.6 months vs. 5.6 months). ORR was 62.6% for patients in the talazoparib arm versus 27.2% in the physician’s choice arm. Patients on talazoparib experienced clinical deterioration in 24.3 months versus 6.3 months for patients on standard chemotherapy. Fifty-five percent of patients on talazoparib versus 39% of those on physician’s treatment of choice experienced grade 3 to 4 adverse events. Litton concluded that talazoparib provides a significant option for patients with metastatic breast cancer and BRCA mutations, and she is optimistic about following the overall survival results as the data mature.
The debate about extending the use of aromatase inhibitors 2 or 5 years after the initial 5 years of adjuvant endocrine therapy continued at this symposium. Michael Gnant, MD, reported on the ABCSG-16 trial of postmenopausal women with hormone receptor–positive breast cancer, which showed that taking anastrazole for 2 years after an initial 5 years of adjuvant endocrine therapy had equal benefit to taking anastrazole for 5 additional years. Furthermore, taking anastrazole for a longer period may be a risk factor for fractures, given the increase in bone fractures in years 3–5 after randomization. The debate continues, and each patient should be evaluated for possible continuation of anastrazole.
Immunotherapy continues to be highly studied in breast cancer patients. Sherene Loi, MD, presented data on the PANACEA trial using pembrolizumab with trastuzumab in patients with trastuzumab-resistant human epidermal growth factor receptor 2 (HER-2)–positive metastatic breast cancer. The combination had clinical benefit in programmed death-ligand 1 (PD-L1)–positive patients and was well tolerated. The trial met its primary end point with an ORR of 15% and a disease control rate of 25% in the PD-L1–positive patients. No response was seen in PD-L1–negative patients.
The 2018 San Antonio Breast Cancer Symposium will be held December 4–8. For more information, visit https://www.sabcs.org.