Trodelvy Plus Keytruda Shows Lasting Benefit in Metastatic Breast Cancer

Treatment with Trodelvy (sacituzumab govitecan) plus Keytruda (pembrolizumab) continued to provide benefits beyond first disease progression for patients with PD-L1-positive metastatic triple-negative breast cancer (mTNBC), according to updated findings from the phase 3 ASCENT-04 trial presented at the 2026 ASCO Annual Meeting.

"In this analysis, PFS2 was improved in the Trodelvy plus Keytruda arm despite a large number of patients in the control arm going on to receive Trodelvy in the second-line setting," lead study author Dr. Kevin Kalinsky, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, said in a presentation of the findings. "This suggests that the benefit of giving Keytruda plus Trodelvy as first-line therapy over chemotherapy is sustained in the long term, further supporting this combination as a potential new standard of care."

How Did Trodelvy Plus Keytruda Affect PFS2 in Metastatic Triple-Negative Breast Cancer?

The updated analysis evaluated progression-free survival 2 (PFS2), which measures the time from randomization until cancer progression on the next line of therapy or death. Researchers consider PFS2 an emerging endpoint that is closely associated with overall survival.

The trial enrolled 443 patients from 26 countries with previously untreated PD-L1-positive metastatic triple-negative breast cancer or locally advanced triple-negative breast cancer that could not be removed with surgery.

Patients were randomly assigned to receive either:

• Trodelvy plus Keytruda (221 patients), or
• Chemotherapy plus Keytruda (222 patients)

Patients in the chemotherapy arm were allowed to receive Trodelvy after disease progression.

At a median follow-up of 14 months, 43% of patients receiving Trodelvy plus Keytruda remained on their initial treatment compared with 23% of patients receiving chemotherapy plus Keytruda.

Among patients who discontinued treatment, 69 of 125 patients in the Trodelvy arm received subsequent treatment. In the chemotherapy arm, 119 of 170 patients received subsequent treatment, and 81% of those patients crossed over to receive Trodelvy.

Despite this crossover, investigators observed a significant improvement in PFS2 among patients who received Trodelvy plus Keytruda.

The median PFS2 had not yet been reached in the Trodelvy arm. By comparison, median PFS2 was 21 months in the chemotherapy arm.

Researchers also reported higher PFS2 rates over time among patients treated with Trodelvy plus Keytruda:

• At 1 year: 80.0% versus 75.7%
• At 18 months: 71.9% versus 53.0%
• At 2 years: 63.7% versus 45.6%

ASCO expert Dr. Eleonora Teplinsky said the findings suggest the benefits of the combination continue even after patients move on to additional therapy.

"Updated results from ASCENT-04 show that the benefit of Trodelvy plus Keytruda persisted beyond first disease progression with improvement in progression-free survival 2 and median time to first subsequent treatment, despite the crossover design of the trial and Trodelvy being the most commonly used second-line therapy among patients in the chemotherapy plus Keytruda arm," Teplinsky said in a statement accompanying the data release.

How Long Did Patients Go Before Needing Another Treatment?

The analysis also showed that patients receiving Trodelvy plus Keytruda went longer before needing another therapy.

The median time to first subsequent treatment was:

• 17.3 months with Trodelvy plus Keytruda
• 9.8 months with chemotherapy plus Keytruda

According to investigators, these findings suggest that using Trodelvy earlier in treatment may provide benefits that extend beyond initial disease control.

During an interview at ASCO, Kalinsky said the updated findings reinforce the clinical benefit observed with the combination.

"The nice thing is that in totality, even when we look at time to first subsequent therapy or time to second subsequent therapy, we're seeing that Trodelvy plus Keytruda is offering clinical benefit for our patients," Kalinsky said.

Trial Details

Triple-negative breast cancer accounts for up to 15% of breast cancer diagnoses and is considered the most aggressive subtype of breast cancer. Approximately 40% of patients with metastatic triple-negative breast cancer have tumors that express PD-L1.

The initial ASCENT-04 analysis demonstrated that Trodelvy plus Keytruda significantly improved progression-free survival compared with chemotherapy plus Keytruda in the first-line setting.

The current analysis was designed to determine whether those benefits persisted after disease progression, particularly because many patients in the control group later received Trodelvy.

Researchers found that both PFS2 and time to first subsequent treatment continued to favor the Trodelvy combination, supporting its use as a frontline treatment option for patients with PD-L1-positive metastatic triple-negative breast cancer.

Safety

Safety findings were not reported as part of this updated analysis.

References

1. Updated progression-free survival 2 results from the phase 3 ASCENT-04 trial of sacituzumab govitecan plus pembrolizumab versus chemotherapy plus Keytruda in patients with previously untreated PD-L1-positive metastatic triple-negative breast cancer. Kevin Kalinsky et al. Presented at the 2026 American Society of Clinical Oncology Annual Meeting.

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