Dr Tolaney on the Effects of Depth of Response on T-DXd/Pertuzumab Treatment Outcomes in DESTINY-Breast09

“It does take time to get deep responses, but the message I took home was [that] deep responses matter because [they are] associated with good PFS.”

Sara M. Tolaney, MD, MPH, a senior physician, chief of the Division of Breast Oncology, and associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute; as well as an associate professor of medicine at Harvard Medical School, discussed the clinical implications of an exploratory analysis from the phase 3 DESTINY-Breast09 trial (NCT04784715) that investigated the relationship between depth of response and progression-free survival (PFS) in patients with HER2-positive advanced or metastatic breast cancer receiving the combination of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and pertuzumab (Perjeta).

The analysis addressed the question of whether the magnitude of tumor shrinkage serves as a reliable predictor for long-term clinical outcomes and PFS in advanced breast cancer. Tolaney began by explaining the refined criteria used to evaluate patient outcomes beyond the standard RECIST definitions, which typically only distinguish between complete responses (CRs) and partial responses (PR). The study identified a deep PR category for patients achieving 80% to 99% tumor reduction. Patients who experienced a reduction of at least 30% but did not meet the “deep” threshold were classified as “other PR,” and the remaining patients were categorized as having stable or progressive disease. Tolaney noted that distinguishing between these levels of PR is essential for a more granular understanding of how different degrees of tumor burden reduction affect the patient's therapeutic trajectory.

Furthermore, Tolaney focused on the therapeutic paradigm regarding the duration of treatment required to achieve a maximal response. She detailed the discovery that these deep responses with T-DXd plus pertuzumab are not typically rapid occurrences; the median time to achieve a CR (n = 58) was 8.4 months (95% CI, 5.6-11.1), whereas reaching a deep PR (n = 141) took a median of 9.6 months (95% CI, 6.8-11.0). Tolaney emphasized that patience is key when using these therapeutic regimens, as the data indicated that 80% of patients in the intention-to-treat population (n = 377) did not reach their maximal tumor reduction until 24 months of treatment. She concluded that recognizing this extended timeline is a critical advancement for the field, as it indicates that the full benefit of therapy may take significant time to manifest.