Dr Tolaney on Implications of Data for Sacituzumab Govitecan in First-line Advanced TNBC

“We did see that the [time to second progression] is substantially longer in the sacituzumab arm compared [with] the chemotherapy arm, which is really reassuring, suggesting that those patients getting sacituzumab govitecan continue to do well, even beyond that first line of treatment.”

Sara Tolaney, MD, MPH, chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, reviewed the efficacy data and clinical implications of the phase 3 ASCENT-03 trial (NCT05382299), which evaluated sacituzumab govitecan-hziy in the first-line treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who were ineligible for immunotherapy.

ASCENT-03 was a randomized study comparing sacituzumab govitecan with chemotherapy of physician’s choice, which included paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin. Patients randomly assigned to the chemotherapy arm were offered sacituzumab govitecan at the time of confirmed progression, allowing for planned crossover.

The primary end point was progression-free survival (PFS) assessed by blinded independent central review. Tolaney noted that sacituzumab govitecan demonstrated a statistically significant improvement in PFS compared with chemotherapy, with a median PFS of 9.7 months (95% CI, 8.1-11.1) with sacituzumab govitecan vs 6.9 months (95% CI, 5.6-8.2) with chemotherapy (HR, 0.62; 95% CI, 0.50-0.77; P < .001). She emphasized that achieving this magnitude of PFS benefit in first-line TNBC, an aggressive subtype with historically limited frontline options, is clinically meaningful.

PFS rates at fixed time points also favored sacituzumab govitecan. At 6 months, the PFS rate was 65% (95% CI, 59%-71%) with sacituzumab govitecan vs 53% (95% CI, 47%-59%) with chemotherapy. At 12 months, PFS rates were 41% (95% CI, 34%-47%) and 24% (95% CI, 19%-30%), respectively.

Overall survival (OS) data remained immature at the time of data readout during the 2025 ESMO Congress. Early OS results appeared similar between arms, likely influenced by the crossover design, in which patients progressing on chemotherapy subsequently received sacituzumab govitecan. Tolaney indicated that longer follow-up will be needed to determine whether OS differences emerge once survival curves mature.

ASCENT-03 also evaluated time to second progression (PFS2), defined as the time from randomization to progression on the next line of therapy. PFS2 was substantially longer for patients treated with sacituzumab govitecan (HR, 0.70; 95% CI, 0.55-0.90), suggesting that early use of the antibody-drug conjugate may provide sustained disease control extending beyond first-line treatment.

Tolaney concluded that ASCENT-03 establishes sacituzumab govitecan as an effective first-line option for patients with advanced TNBC who are not eligible for immunotherapy, and mature OS data will further clarify the long-term impact of incorporating sacituzumab govitecan earlier in the treatment sequence.