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Q: Could you summarize the magnitude of benefit seen with Dato-DXd compared to chemotherapy in this first-line mTNBC population and comment on how clinically meaningful this is for practice?
Rebecca Dent, MD: As we know, patients with metastatic triple-negative breast cancer—especially those who are not eligible for immune checkpoint inhibition, which represents about 60% to 70% of patients we see in the first-line setting—have had chemotherapy as the standard of care for well over 10 years. In this setting, 50% of patients progress and never go on to receive second-line therapy. So there was a real need to incorporate a novel therapy into the first-line setting.

In addition, patients are receiving more treatment in the curative setting, and so if they relapse, they’ve already seen a number of different chemotherapies. What’s unique about TROPION-Breast02 is that we are incorporating an antibody-drug conjugate as the first-line therapy in patients with relapsed or de novo metastatic TNBC, or those relapsing more than 12 months after initial therapy.

Here we saw the use of Dato-DXd, a TROP2-directed antibody-drug conjugate with a potent topoisomerase payload and a stable, cleavable linker. Because of the drug-to-antibody ratio, we see potent effectiveness in terms of improvements in progression-free survival (PFS), with a safety profile that allows administration every three weeks, which is very convenient for patients.

We saw an impressive improvement in PFS—from about 5 months to over 10 months in median PFS, a delta of more than 5 months. These Kaplan-Meier curves separate very early, with a time to treatment response of 1.4 months, and the curves continue to separate and remain sustained.

We also saw an improvement in overall survival (OS). Median OS was 18.7 months with standard chemotherapy and increased to almost 2 years with Dato-DXd—a delta of 5 months, with a statistically significant hazard ratio.

The data were very consistent. In clinic, what’s extraordinary is seeing such a visible improvement in response. We saw more than a doubling of response rates with Dato-DXd compared with chemotherapy—well over 60%, a delta of more than 30%, and a tripling of the complete response rate.

What’s even more helpful in clinic is that these responses are sustained. Often, we can achieve a response, but it doesn’t last. In this trial, duration of response increased from 7 months with chemotherapy to more than 12 months with Dato-DXd—again, a 5-month improvement. So across endpoints—PFS, OS, and duration of response—we consistently saw about a 5-month delta favoring Dato-DXd.