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Jason A. Mouabbi, MD, discusses the importance of achieving consensus for integrating CompassHER2-pCR data into early-stage HER2+ breast cancer management.
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"With every major meeting, we get new data, and these data are very important to digest and to reach consensus [about]. The problem is, with new data, there are new controversies, and a lot of time, treating physicians in the community especially are stuck trying to figure out which treatment [they] should give to their patients."
Jason A. Mouabbi, MD, an assistant professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center, discussed the clinical and practical significance of achieving consensus regarding the integration of data from the phase 2 CompassHER2-pCR trial (NCT04266249) into treatment algorithms for early-stage HER2-positive breast cancer.
The CompassHER2-pCR trial evaluated neoadjuvant treatment de-escalation by omitting carboplatin and shortening therapy duration, investigating the effects of this neoadjuvant therapy on pathologic complete response (pCR) rates at surgery. Specifically, the study examined the efficacy of a neoadjuvant 4-cycle regimen of docetaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP) compared with the historical 6-cycle docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) regimen. The findings suggested that the THP regimen maintained pCR rates and early efficacy outcomes in patients with stage II and selected stage IIIA disease, without the added toxicity of carboplatin.
A parallel trial, the phase 3 neoCARHP study (NCT04858529), explored a similar de-escalation strategy, maintaining 6 cycles of THP in place of TCHP in patients with HER2-positive breast cancer. Both studies provided evidence supporting the removal of carboplatin in appropriately selected patients, indicating that platinum-based agents may no longer be necessary for many patients in this setting.
Mouabbi emphasized that carboplatin, although effective, contributes significant hematologic and nonhematologic toxicity. Its exclusion could improve tolerability without compromising long-term outcomes, especially for patients who achieve a pCR after neoadjuvant therapy. He noted that the increasing availability of treatment options—and corresponding data—can create uncertainty among community oncologists, underscoring the importance of consensus-building efforts at national meetings and through forthcoming manuscripts.
Mouabbi stressed that establishing uniform guidance is particularly important given the evolving HER2-positive breast cancer treatment paradigm. Without clear consensus, oncologists are left to interpret emerging evidence independently, which may lead to variation in care, according to Mouabbi. As such, aligning practice around data from CompassHER2-pCR is essential to streamline clinical decisions and support safe, evidence-based de-escalation, he reported.
Although the CompassHER2-pCR data are most compelling in patients with stage II and IIIA disease, Mouabbi acknowledged that additional research is needed for patients with stage IIIB and IIIC tumors, where de-escalation remains less clearly defined. Still, he noted that carboplatin is likely to fall out of favor in the neoadjuvant setting for the broader HER2-positive population. Mouabbi concluded that CompassHER2-pCR provides a strong foundation for refining HER2-positive breast cancer management and moving toward less toxic, more patient-centric care.
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