CHICAGO -- First-line treatment with sacituzumab govitecan plus pembrolizumab showed significant improvement in PFS vs. chemotherapy plus pembrolizumab among patients with metastatic triple-negative PD-L1-positive breast cancer.
Primary results from the global, randomized, phase 3 ASCENT-04/KEYNOTE-D19 trial, presented at ASCO Annual Meeting, also showed no new safety issues with sacituzumab govitecan (Trodelvy, Gilead Sciences) plus pembrolizumab (Keytruda, Merck) and a low rate of treatment discontinuation due to treatment-related adverse events.
"The combination of sacituzumab govitecan plus pembrolizumab could be considered a potentially new first-line standard of care, since it is doing much better than the current standard-of-care treatment we have for patients with PD-L1-positive metastatic triple-negative breast cancer," Sara M. Tolaney, MD, MPH, chief of the division of breast oncology and associate director of Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, associate professor of medicine at Harvard Medical School, and Healio Women in Oncology Peer Perspective Board member, told Healio.
"Essentially, there was a 35% reduction in the risk of disease progression or death with sacituzumab govitecan plus pembrolizumab compared with chemotherapy plus pembrolizumab, with benefit seen across key subgroups of patients in this trial."
Although PD-1/PD-L1 inhibitors plus chemotherapy have expanded treatment options for patients with previously untreated PD-L1-positive advanced triple-negative breast cancer, there remains a critical unmet need to improve outcomes, according to Tolaney.
"About half of [these] patients who receive treatment in the first-line setting are not able to go on to receive second-line therapy, either due to deterioration in health or death," she said during a press briefing. "There's been much interest in trying to combine antibody-drug conjugates with checkpoint inhibition given robust preclinical and clinical data for the combination.
"Sacituzumab govitecan previously demonstrated improvements in PFS and OS in patients with pretreated metastatic triple-negative disease and is currently approved as a second-line or later treatment option for patients with metastatic triple-negative breast cancer."
Tolaney and colleagues randomly assigned 443 patients 1:1 to either 10 mg/kg sacituzumab govitecan on days 1 and 8 plus 200 mg pembrolizumab on day 1 (21-day cycles; maximum 35 cycles; n = 221; median age, 54 years; range, 23-88; 63% white) or gemcitabine plus carboplatin, paclitaxel, nab-paclitaxel (chemotherapy regimen) plus pembrolizumab (n = 222; median age, 55 years; range, 27-82; 53% white) until disease progression or unacceptable toxicity.
The researchers stratified patients based on curative treatment-free interval, geography and prior exposure to anti-PD-L1 therapy in the curative setting.
PFS by blinded independent central review served as the primary endpoint. Secondary endpoints included OS, objective response rate, duration of response and safety.
At median follow-up of 14 months, researchers observed a significant improvement in PFS from a median 11.2 months with sacituzumab govitecan plus pembrolizumab compared with 7.8 months with chemotherapy plus pembrolizumab (HR = 0.65; 95% CI, 0.51-0.84).
They additionally observed a median duration of response of 16.5 months in the sacituzumab govitecan group compared with 9.2 months in the chemotherapy group. Objective response rate was 60% (95% CI, 52.9%-66.3%) with the sacituzumab govitecan combination vs. 53% (95% CI, 46.4%-59.9%) with the chemotherapy combination.
Results additionally showed a complete response rate of 13% with the sacituzumab govitecan combination vs. 8% with the chemotherapy combination.
Tolaney also noted that early data showed a positive trend toward improved OS.
"While OS data remain immature, with just 26% of survival events having occurred at the time of this data analysis, there is a trend in improvement favoring sacituzumab govitecan plus pembrolizumab compared with chemotherapy plus pembrolizumab, with an HR of 0.89," she added. "Of note, at the time of data log, 43% of patients in the chemotherapy plus pembrolizumab group elected to crossover and receive second-line treatment with sacituzumab govitecan. This represents about 80% of patients who received a subsequent treatment after discontinuation of chemotherapy plus pembrolizumab."
Common grade 3 or higher treatment-emergent adverse events associated with the sacituzumab govitecan combination included neutropenia (43%) and diarrhea (10%). The most frequent events in the chemotherapy combination group were neutropenia (45%), anemia (16%) and thrombocytopenia (14%).
"The safety profile for sacituzumab govitecan plus pembrolizumab was consistent with the established toxicities that are seen with each agent, suggesting no additive toxicities," Tolaney said.
ASCO expert Jane L. Meisel, MD, FASCO, co-director of breast medical oncology at Winship Cancer Institute of Emory University School of Medicine, said these data are potentially practice changing.
"We have seen in previous studies how sacituzumab govitecan can work so well for patients with metastatic triple-negative breast cancer later on in their treatment and now to see this combined with pembrolizumab and compared to chemotherapy plus pembrolizumab with such both statistically and clinically meaningful benefits for patients, really does change the game for this subgroup. I look forward to seeing this potentially make its way into clinical practice," she said.