Dr Tarantino on the Efficacy of Adjuvant THP in HER2+ Breast Cancer

“The biology of the tumor drove the activity of THP."

Paolo Tarantino, MD, PhD, a research fellow in the Department of Medicine at Dana-Farber Cancer Institute and Harvard Medical School, discussed findings from the phase 2 CompassHER2 pCR trial (NCT04266249) evaluating the use of de-escalated adjuvant therapy with a taxane with trastuzumab (Herceptin) and pertuzumab (Perjeta; THP) in patients with stage II to IIIA HER2-positive breast cancer who have no cancer remaining at surgery following neoadjuvant chemotherapy and HER2-targeted therapy.

The study demonstrated a pathologic complete response (pCR) rate of 43.8% (95% CI, 41.6%-45.9%) in all patients (n = 2141)with only 12 weeks of neoadjuvant THP use. Notably, the pCR rate was higher among patients with HER2 3+ disease, particularly those with estrogen receptor (ER)–negative tumors, indicating that tumors highly dependent on HER2 signaling are more responsive to THP, according to Tarantino. An additional observation was that patients treated with paclitaxel achieved superior pCR rates compared with those treated with docetaxel, suggesting differential efficacy between these 2 taxanes in this setting, he noted. Importantly, traditional clinical parameters, including tumor size, clinical stage, and nodal involvement, were not predictive of pCR, he explained. Instead, tumor biology emerged as the primary determinant of response to THP, he summarized.

Although survival outcomes from this trial are not yet available and follow-up is ongoing, the finding that more than 40 percent of patients overall—and 63.7% (95% CI, 60.2%-67.1%) of those with ER-negative disease—achieved a pCR after only 12 weeks of therapy is encouraging, Tarantino continued. This outcome suggests that THP could represent a clinically meaningful alternative to the conventional regimen of a taxane, carboplatin, trastuzumab, and pertuzumab, which typically requires 18 weeks of therapy and is associated with additional toxicity, he said. THP had both significant efficacy and favorable tolerability in this study, offering a potentially less intensive treatment option without compromising therapeutic benefit, he emphasized.

Additionally, exploratory data were collected with HER2DX, a genomic classifier that integrates multiple biological dimensions,including HER2 addiction, luminal proliferation, and tumor immune profile, Tarantino stated. This assay stratified patients according to their likelihood of achieving pCR with neoadjuvant THP, effectively identifying those most likely to benefit, he reported. These findings underscore the potential of HER2DX score as a predictive biomarker that could eventually guide treatment individualization, he contextualized.