Dr Gluz on Survival Outcomes With De-Escalated Neoadjuvant Regimens in HR+/HER2+ Early Breast Cancerer

Oleg Gluz, MD, chief physician, Breast Center Niederrhein; West German Study Group, discusses survival data from the phase 2 WSG-TP-II trial (NCT03272477) of neoadjuvant endocrine therapy plus trastuzumab (Herceptin) and pertuzumab (Perjeta) in hormone receptor (HR)–positive, HER2-positive early breast cancer.

The WSG-TP II trial is the first prospective, multicenter, randomized study comparing the survival outcomes of two 12-week de-escalated regimens in patients with stages I through III HR-positive, HER2-positive breast cancer: neoadjuvant endocrine therapy plus trastuzumab and pertuzumab vs paclitaxel plus trastuzumab and pertuzumab. The trial's primary goal was to determine if patients could safely omit further adjuvant chemotherapy if they achieved a pathological complete response (pCR) following the 12-week neoadjuvant treatment.

Results presented at the 2024 ESMO Congress demonstrated the high efficacy and tolerability of the 12-week regimen, particularly when combining paclitaxel with trastuzumab and pertuzumab, Gluz reports. Notably, pCR rates were higher in patients receiving de-escalated chemotherapy vs those receiving the endocrine therapy regimen, he adds. Across all patients, approximately two-thirds achieved pCR after 12 weeks of treatment, emphasizing the efficacy of the chemotherapy-based approach, Gluz states.

However, long-term survival outcomes were comparable between both treated arms, Gluz continues. The 5-year event-free survival rates were 92.1% vs 94.8% with the endocrine- vs chemotherapy-based regimens, respectively. Respective overall survival (OS) rates for these arms were 100% vs 97.9%. These findings suggest that starting with a de-escalated treatment 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, he explains.

Overall, these results suggest that it is safe and feasible to begin treatment with 12 weeks of a fixed chemotherapy backbone plus double blockade in HR-positive, HER2-positive breast cancer, administering chemotherapy only to patient who do not achieve responses with the de-escalated approach, Gluz concludes.