The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Additional trial results revealed that de-escalated neoadjuvant weekly paclitaxel and dual human epidermal growth factor receptor 2 (HER2) blockade led to excellent pathologic complete response (pCR) and survival in patients with hormone receptor–negative (HR-), HER2-positive (HER2+) early breast cancer. These findings were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Previous results of the prospective, multicenter WSG-ADAPT phase 2/3 trial ( Identifier: NCT01779206) revealed an excellent pCR rate of 90% after only 12 weeks of treatment with neoadjuvant paclitaxel plus pertuzumab and trastuzumab. A clinically meaningful pCR rate of 34% following treatment with P+T alone in HR-/HER2+ early breast cancer was also reported. Nadia Harbeck, MD, of Brustzentrum der Universität München (LMU) in Germany reported additional biomarker and survival results of the ADAPT-HR-/HER2+ study ( Identifier: NCT01966471).

The WSG-ADAPT-HR-/HER2+ study randomly assigned 134 patients to receive pertuzumab plus trastuzumab (92 patients) or pertuzumab plus trastuzumab with paclitaxel (42 patients); 60% of the patients had cT2-4 tumors and 42% were lymph node–positive. The primary endpoint was pCR, and secondary endpoints were invasive disease-free survival (iDFS), overall survival (OS), and safety.

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After a median follow-up of 5 years, there were no significant differences in distant DFS (dDFS), iDFS, or OS between the 2 study arms. Only 13 iDFS events were noted in the intention-to-treat population. Following 12 weeks of treatment, pCR was found to be strongly associated with improved iDFS (5 year DFS, 98.5% vs 82%; hazard ratio [HR], 0.14; 95% CI, 0.03-0.64).

A total of 69 patients achieved pCR, of which 56.5% did not receive further chemotherapy (CT; 29% in pertuzumab plus trastuzumab arm and 79% in pertuzumab plus trastuzumab with paclitaxel arm); only 1 patient had distant relapse (1.4%). In the CT-free pertuzumab plus trastuzumab arm, patients with low HER2 expression did not achieve pCR. Low HER2 expression and/or no early response were strongly associated with worse dDFS (P =.029) and iDFS (P =.068). No new safety concerns were identified during the study.

Overall, the ADAPT HR-/HER2+ showed early pCR after only 12 weeks of neoadjuvant pertuzumab plus trastuzumab with paclitaxel, which was strongly associated with improved outcome and may thus serve as a predictive clinical marker for further treatment de-escalation.

“These findings are highly encouraging, particularly since the majority of patients in this study had stage 2 or 3 disease, and outside of this study, they would be subjected to a more aggressive and toxic standard-of-care regimen. This study indicates that we may be able to use early pCR as a predictor of good outcomes, and that achieving this might reasonably allow for further treatment de-escalation. The study also sheds more light on the potential for chemo-free regimens for certain subsets of the HER2+ population,” said Jane Lowe Meisel, MD, of the Emory University School of Medicine in Atlanta, Georgia

Disclosure: This research was supported by Roche, AOK. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Harbeck N, Gluz O, Christgen M, et al. De-escalated neoadjuvant pertuzumab+trastuzumab with or without paclitaxel weekly in HR-/HER2+ early breast cancer: ADAPT-HR-/HER2+ biomarker and survival results. J Clin Oncol. 2021;39:(suppl 15; abstr 503). doi:10.1200/JCO.2021.39.15_suppl.503