More Data Support Trodelvy-Keytruda Combo in Triple-Negative Breast Cancer

CHICAGO — Sacituzumab govitecan (SG, Trodelvy) added to pembrolizumab (Keytruda) extended a surrogate measure of long-term clinical outcomes compared with chemotherapy plus pembrolizumab in patients with PD-L1-positive metastatic triple negative breast cancer (mTNBC), according to an analysis of the phase III ASCENT-04 trial.

Median progression-free survival after the next line of treatment (PFS2) was not reached in the SG arm at a median follow-up of 14 months, whereas PFS2 was 21 months in the chemotherapy group. This difference represented a 33% reduction in risk (HR 0.67, 95% CI 0.48-0.95), Kevin Kalinsky, MD, MS, of the Winship Cancer Institute of Emory University in Atlanta, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The median rate of PFS2 — an endpoint that combines cancer growth following second-line therapy and death from any cause — was higher in the SG group than in the chemotherapy group at 1 year (80.0% vs 75.7%), 18 months (71.9% vs 53.0%), and 2 years (63.7% vs 45.6%).

“PFS2 can be used to measure long-term clinical benefit in the absence of mature overall survival (OS) data and is particularly valuable when OS is confounded by a crossover design,” as in ASCENT-04, said Kalinsky at an ASCO press briefing.

The findings build on primary endpoint data from ASCENT-04 that showed superior PFS with SG plus pembrolizumab as first-line treatment in mTNBC and support the combination as a potential new standard for first-line treatment, according to Kalinsky.

“The reason this [analysis] is so important is that a significant amount of patients are not able to receive subsequent lines of therapy for metastatic triple negative breast cancer,” commented Eleonora Teplinsky, MD, from Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, who was not involved with the study. “This PFS2 analysis supports the long-term clinical benefit and shows us that what we were giving in the first line makes a difference towards sustained benefit in subsequent lines of therapy. I think this is critically important, and hopefully, we’ll provide a new standard of care for our patients.”

The difference in PFS2 between the arms occurred despite a high rate of crossover from chemotherapy to SG. Almost twice as many participants in the SG plus pembrolizumab group remained on study treatment compared with those in the chemotherapy plus pembrolizumab group (43% vs 23%) at the time of data cutoff.

Of the 170 patients in the chemotherapy arm who discontinued their first-line treatment, 119 (70%) received subsequent treatment, 81% of whom received SG as their second line of treatment. A total of 69 (55%) patients randomized to SG plus pembrolizumab received second-line or later treatment, 88% of whom received chemotherapy.

Overall, the median time to the first subsequent therapy was 17.3 months in the SG group versus 9.8 months in the chemotherapy arm. “Time to first and second subsequent therapies suggest that participants receiving first-line sacituzumab govitecan plus pembrolizumab experience longer initial disease control and delayed need for subsequent therapy,” Kalinsky said.

The global ASCENT-04 trial included 443 patients with previously untreated locally advanced unresectable or mTNBC whose tumors were positive for PD-L1 (combined positive score ≥10) and who were at least 6 months out after treatment in a curative setting. These patients were randomized to SG plus pembrolizumab or chemotherapy plus pembrolizumab. Treatment was continued until disease progression or unacceptable toxicity.

SG plus pembrolizumab demonstrated statistically significant and clinically meaningful improvement in PFS versus chemotherapy plus pembrolizumab. OS data were immature at the primary analysis; however, a trend in improvement was observed for SG plus pembrolizumab. PFS2 was an exploratory endpoint.

No new safety concerns with SG or pembrolizumab were apparent at the time of the updated analysis.