Dr Gluz on Predictive Biomarkers for pCR With De-Escalated Chemo in HER2+ Breast Cancer

"There were several markers which are clearly predictive for pCR after 12 weeks [with de-escalated chemotherapy in patients with HR+ HER2+ early breast cancer]. For example, HER2 expression was found to be a clear predictive marker."

Oleg Gluz, MD, chief physician of Breast Cancer Niederrhein, discusses efficacy findings from the phase 2 WSG-TP-II trial (NCT03272477) across subgroups of patients with hormone receptor–positive, HER2-positive early breast cancer who received a de-escalated chemotherapy regimen in the neoadjuvant setting.

WSG-TP-II evaluated the efficacy of neoadjuvant endocrine therapy in combination with trastuzumab (Herceptin) and pertuzumab (Perjeta) vs de-escalated chemotherapy plus trastuzumab and pertuzumab in patients with hormone receptor–positive, HER2-positive early breast cancer. Results from this study showed that the incidence of early pathologic complete responses (pCRs) was higher in patients from the de-escalated chemotherapy arm (n = 100) vs the endocrine therapy arm (n = 107), with 57 and 23 pCR cases in each respective arm at 12 weeks. Furthermore, the 5-year event-free survival rates were 94.8% and 92.1% in these respective arms (HR, 1.29; 95% CI, 0.26%-2.32%; P = .65). The 5-year overall survival rates were 100% and 97.9%, respectively.

Investigators identified several predictive biomarkers for pCR following 12 weeks of de-escalated chemotherapy, Gluz says. Among these, HER2 expression was confirmed as a strong predictive marker, he notes.

An analysis of survival outcomes revealed no significant differences in prognosis among patient subgroups, he explains. However, baseline characteristics indicated that most patients enrolled in the trial had stage IIA disease, characterized by tumors larger than 2 cm without nodal involvement, or smaller tumors with 1 positive lymph node, he states. Given the prevalence of such cases in clinical practice, these findings suggest that de-escalated chemotherapy could be a viable treatment approach for this patient population, Gluz emphasizes.

Conversely, patients presenting with locally advanced disease, including those with tumors larger than 5 cm or those with more than 4 positive lymph nodes, were underrepresented in the trial, he reports. Given the high tumor burden in these patients, Gluz advises caution when considering chemotherapy de-escalation in this subgroup, as they may not be optimal candidates for this approach.