The phase 2 WSG-TP-II trial (NCT03272477) reveals that de-escalated neoadjuvant therapy with endocrine therapy plus trastuzumab and pertuzumab yields comparable survival outcomes to paclitaxel plus trastuzumab and pertuzumab in patients with hormone receptor (HR)-positive, HER2-positive early breast cancer. The findings, presented at the 2024 ESMO Congress, suggest a potential shift in treatment strategies, reserving chemotherapy for those who do not respond to the de-escalated regimen.
Study Design and Rationale
The WSG-TP-II trial, a prospective, multicenter, randomized study, aimed to determine if adjuvant chemotherapy could be safely omitted in patients achieving a pathological complete response (pCR) following 12 weeks of neoadjuvant treatment. The trial enrolled patients with stages I through III HR-positive, HER2-positive breast cancer, randomizing them to either neoadjuvant endocrine therapy plus trastuzumab and pertuzumab or paclitaxel plus trastuzumab and pertuzumab.
The rationale behind the study was to explore treatment de-escalation strategies, given the potential adverse effects and burden associated with traditional 18 to 24 week chemotherapy regimens combined with trastuzumab and pertuzumab. Initiated in 2016, the trial sought to evaluate the possibility of safely reducing or eliminating one component of the standard treatment regimen without compromising efficacy.
Efficacy and Tolerability
While pathological complete response (pCR) rates were higher in the chemotherapy arm, long-term survival outcomes were comparable between the two treatment arms. Approximately two-thirds of all patients achieved pCR after 12 weeks, with the chemotherapy-based approach showing higher pCR rates. However, the 5-year event-free survival rates were 92.1% in the endocrine therapy arm and 94.8% in the chemotherapy arm. The overall survival rates were 100% and 97.9%, respectively, demonstrating that initiating treatment with de-escalated endocrine therapy plus dual HER2 blockade is a safe approach.
Clinical Implications
According to Dr. Oleg Gluz, chief physician at Breast Center Niederrhein, West German Study Group, these findings suggest that a de-escalated treatment approach of endocrine therapy plus double HER2 blockade is safe, and chemotherapy can be reserved for patients who do not respond to the de-escalated regimen. The results indicate the feasibility of starting with 12 weeks of a fixed chemotherapy backbone plus double blockade in HR-positive, HER2-positive breast cancer, administering chemotherapy only to patients who do not achieve responses with the de-escalated approach.
Following surgery, patients received one year of standard adjuvant endocrine therapy plus trastuzumab and pertuzumab, with or without chemotherapy. The study protocol strongly recommended omitting adjuvant chemotherapy for patients who achieved pCR after 12 weeks of neoadjuvant treatment, while those who did not achieve pCR were recommended to receive adjuvant chemotherapy. This approach underscores the potential for personalized treatment strategies based on early response to therapy.
