Patients with hormone receptor-positive (HR+)/HER2+ early breast cancer treated with neoadjuvant endocrine therapy or chemotherapy plus trastuzumab and pertuzumab, followed by adjuvant pathological complete response (pCR)-guided chemotherapy and adjuvant trastuzumab and pertuzumab plus endocrine therapy, experienced exceptionally excellent survival outcomes. These findings from the phase 2 WSG-TP II trial were presented at the 2024 ESMO Annual Congress.
The WSG-TP II trial is reported to be the first prospective survival comparison for endocrine therapy plus trastuzumab and pertuzumab compared with a chemotherapy-based regimen in HER2+/HR+ early breast cancer. The study highlights the potential for chemotherapy de-escalation in this patient population, offering a less toxic treatment approach without compromising survival.
Trial Design and Patient Characteristics
The trial enrolled 207 patients with HR+/HER2+ early breast cancer (stages 1 to 3). Participants were allocated to either 12 weeks of neoadjuvant standard endocrine therapy (100 patients) or paclitaxel chemotherapy (107 patients) weekly plus trastuzumab and pertuzumab, followed by standard endocrine therapy for a minimum of five years plus trastuzumab and pertuzumab for a year, with or without adjuvant chemotherapy.
In the endocrine therapy arm, the median patient age was 52 years, 63% of patients had stage 2 or higher disease, and 68% were clinical node negative. In the chemotherapy arm, the median patient age was 54 years, 54% had stage 2 or higher disease, and 76% were clinical node negative.
Key Findings on Survival
For patients who achieved pCR, omission of further adjuvant chemotherapy was recommended. At a median follow-up of 60 months, the five-year event-free survival (EFS) rates for endocrine therapy versus chemotherapy plus trastuzumab and pertuzumab were 92% versus 94.8%. Of the 13 EFS events, one versus four were distant relapses or deaths as the first event in the endocrine therapy versus chemotherapy arms. The five-year overall survival (OS) rates were 100% versus 97.9%, respectively.
According to Dr. Oleg Gluz, of Breast Center Niederrhein in Mönchengladbach, Germany, “In HR+, HER2+ disease, short 12 weeks de-escalated neoadjuvant treatment endocrine therapy or paclitaxel, plus double blockade continued for one year offers a safe opportunity for chemotherapy de-escalation.”
Impact of Nodal Status and Adjuvant Chemotherapy
Clinically node-positive status was the only factor significantly associated with worse EFS by multivariable analysis. Additional chemotherapy after pCR was not associated with a significant survival impact. In the endocrine therapy arm, 29% of patients received no chemotherapy during the trial, and 60% of patients in the chemotherapy-containing arm received only 12 weeks of chemotherapy. Safety was also superior in the endocrine therapy-containing arm, and quality of life was maintained.
