Dr Tolaney on the Clinical Implications of First-Line T-DXd Plus Pertuzumab in HER2+ Breast Cancer

“Seeing that T-DXd and pertuzumab are, in essence, doubling progression-free survival and almost doubling the complete response rate compared with THP, it does mean that this hopefully will become a new standard of care option for our patients.”

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology at Susan F. Smith Center for Women’s Cancers, associate director of the Susan F. Smith Center for Women’s Cancers; a senior physician at Dana-Farber Cancer Institute; and associate professor of medicine at Harvard Medical School, detailed the clinical implications and safety of first-line fam-trastuzumab deruxtecan-nkki (T-DXd; Enhertu) plus pertuzumab (Perjeta) for the treatment of patients with HER2-positive advanced or metastatic breast cancer.

Data from the phase 3 DESTINY-Breast09 trial (NCT04784715), which is evaluating T-DXd plus pertuzumab in patients with HER2-positive advanced or metastatic breast cancer, has demonstrated significant improvements in progression-free survival (PFS) and overall response rate (ORR), particularly regarding complete responses (CRs), compared with standard-of-care trastuzumab (Herceptin) plus pertuzumab with a taxane (THP) as first-line treatment, Tolaney began.

Results presented at the 2025 ASCO Annual Meeting showed that patients treated with T-DXd plus pertuzumab achieved a median PFS of 40.7 months (95% CI, 36.5-not calculable [NC]) compared with 26.9 months (95% CI, 21.8-NC) with THP (HR, 0.56; 95% CI, 0.44-0.71; P <.00001).

With these results, Tolaney added that she hopes this regimen become a new standard of care option in the frontline setting for patients with HER2-positive advanced or metastatic breast cancer.

Furthermore, Tolaney emphasized that the adverse effects (AEs) observed with T-DXd plus pertuzumab were consistent with the already-known safety profiles of the respective agents. Of note, the most common AEs included nausea, diarrhea, neutropenia, and grade 3/4 toxicities, she explained. Serious AEs were similar between the T-DXd/pertuzumab and THP arms, with more dose interruptions and reductions observed with T-DXd/pertuzumab vs THP, she added. Additionally, a 12% rate of interstitial lung disease with T-DXd/pertuzumab was reported; however, the majority of these events were low grade. Two grade 5 instances of ILD (0.5%) were reported, Tolaney concluded.