medwireNews: One dose of patritumab deruxtecan (HER3-DXd) induces a clinically meaningful response in women with hormone receptor-positive, HER2-negative (HR+, HER2–) early breast cancer, show data from the SOLTI TOT-HER3 trial.
Furthermore, the response was independent of baseline HER3 gene expression and HER3 protein levels, reported Aleix Prat, from the Hospital Clinic of Barcelona in Spain, at the ESMO Breast Cancer Congress 2022 in Berlin, Germany.
Prat explained that an initial analysis of the first 30 patients enrolled in SOLTI TOT-HER3 demonstrated the biologic and clinical activity of HER3-DXd, a novel HER3-directed antibody–drug conjugate that comprises a human anti-HER3 monoclonal antibody linked to a topoisomerase I inhibitor.
In the current analysis, 77 women (mean age 53 years) with treatment-naïve HR+/HER2– early breast cancer suitable for surgery were evaluated for the primary efficacy endpoint of change in CelTIL score between baseline and 21 days after treatment with a preoperative single dose of HER3-Dx (6.4 mg/kg).
CelTIL is a validated score that measures tumor infiltrating lymphocytes and correlates with pathologic complete response across breast cancer subtypes, Prat said.
The study participants had a median tumor size of 21 mm, 71% were node negative, and the mean Ki67 expression level was 27%. Just over half (52%) of tumors had a luminal A subtype, 41% were luminal B, 4% were basal-like, and 3% were HER2-enriched.
At the end of treatment, the mean CelTIL score was a significant 6.8 percentage points higher than at baseline and the increase was independent of baseline HER3 messenger (m)RNA expression as well as HER3 membrane positivity by immunohistochemistry.
The overall response rate was 45%, which included an equal amount of complete and partial responses.
When the investigators split the cohort by clinical response, they found that the mean increase in CelTIL score from baseline to the end of treatment was a significant 15.2 percentage points in the 28 responders but a nonsignificant 2.9 percentage points among the 34 nonresponders.
Further subgroup analyses revealed that people with non-luminal subtypes and those with high baseline PAM50 Risk Of Recurrence (ROR) score had significantly greater changes in CelTIL score than those with luminal subtypes and medium or low ROR scores, respectively.
Prat also noted that HER3-DXd treatment induced the expression of immune-related genes and suppressed tumor proliferation genes. Overall, Ki67 expression decreased by a significant 9.0 percentage points from baseline to the end of treatment but there was no change in the level of HER3 mRNA.
In terms of safety, the presenter said that the adverse event (AE) “profile was consistent with that previously reported for the drug.” The majority (95%) of patients experienced an AE of any grade and 14% experienced a grade 3 or worse AE, most commonly neutropenia (8%).
The TOT-HER3 trial is now enrolling patients with early-stage triple-negative breast cancer and also exploring a lower dose of HER3-DXd, and another trial – SOLTI-VALENTINE – will test HER3-DXd alone or in combination with endocrine therapy as neoadjuvant treatment in HR+/HER2– early disease, Prat concluded.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group