Patients with localized, hormone receptor-positive, HER2-low breast cancer treated in the neoadjuvant setting with trastuzumab deruxtecan had an overall response rate of 68% in the absence of anastrozole and 58% in combination with anastrozole, first results from the TRIO-US B-12 TALENT trial showed.


 

HER2-low breast cancer is actionable by the antibody-drug conjugate trastuzumab-deruxtecan, as was recently demonstrated in patients with metastatic, HER2-low breast cancer.1 The efficacy of trastuzumab-deruxtecan in localized HER2-low breast cancer is not known.

The investigator-initiated, phase 2 TRIO-US B-12 TALENT trial evaluated the efficacy of  trastuzumab-deruxtecan as a neoadjuvant treatment for patients with localized HR-positive/HER2-low breast cancer. Given the cross-talk between ER and HER2, addition of endocrine therapy to trastuzumab-deruxtecan was also evaluated in this setting. Dr. Aditya Bardia (Harvard Medical School) presented the first results2 at the 2022 San Antonio Breast Cancer Symposium.

Enrolled were 58 patients with HR-positive/HER2-low, stage II or III breast cancer. Patients were randomized 1:1 to receive trastuzumab-deruxtecan (6 or 8 cycles) or trastuzumab-deruxtecan plus anastrozole followed by surgery. The primary objective was to evaluate pathological complete response (pCR) in breast and lymph nodes. Secondary objectives were objective response rate (ORR), change in HER2, and safety.

Of the patients treated with trastuzumab-deruxtecan, 5% achieved pCR (RCB-0) and 10% achieved near-pCR (RCB-I). ORR in these patients was 68% (8% CR). Of the patients treated with trastuzumab-deruxtecan plus anastrozole, 0% achieved pCR and 15% achieved near-pCR. ORR in these patients was 58% (8% CR). At data cut-off, surgical outcomes were pending for 24% of patients treated with trastuzumab-deruxtecan and 31% of patients treated with trastuzumab-deruxtecan plus anastrozole.

“These first results demonstrate preliminary evidence of clinical activity of neoadjuvant trastuzumab-deruxtecan in HR-positive/HER2-low localised breast cancer. Addition of endocrine therapy does not appear to enhance efficacy of trastuzumab-deruxtecan,” concluded Dr. Bardia.

 

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