LARGEST PROSPECTIVE TRIAL OF 12-WEEK NEOADJUVANT TAXANE PLUS DUAL HER2 BLOCKADE CONFIRMS HER2DX PREDICTS RESPONSE IN HER2-POSITIVE BREAST CANCER

• ECOG-ACRIN EA1181/CompassHER2 pCR, the largest prospective trial of 12-week neoadjuvant single taxane, trastuzumab and pertuzumab (THP) in stage II–IIIA HER2-positive breast cancer, has been published in the Journal of Clinical Oncology¹.
• Among 2,141 evaluable patients, the overall pathologic complete response (pCR) rate was 43.8%.
• In a prespecified analysis, pathologic complete response (pCR) rates were 68.0% for HER2DX pCR-high versus 19.0% for pCR-low tumors, a 49-point difference that remained significant after adjustment for clinico pathologic factors, including estrogen receptor (ER) status.

REVEAL GENOMICS,S.L., the creator of HER2DX, highlights the results, published in the Journal of Clinical Oncology of results from ECOG-ACRIN EA1181/CompassHER2 pCR, the largest prospective trial to date evaluating 12-week neoadjuvant THP in stage II–IIIA HER2-positive breast cancer¹. A prespecified biomarker analysis showed that the HER2DXpCR likelihood score independently predicted treatment response.

 EA1181 was independently designed and conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN),with funding from the National Cancer Institute (NCI), and Dr. Nadine M. Tung,MD, from the Beth Israel Deaconess Medical Center (Boston, MA), as the study chair.

The trial enrolled 2,175 patients with stage II–IIIA HER2-positive breast cancer between March 2020 and October 2023. It is the largest prospective study of neoadjuvant THP in this setting and the only one powered to evaluate survival outcomes.

Patients received 12 weeks of a single taxane—weekly paclitaxel,docetaxel every three weeks, or weekly nab-paclitaxel—together with trastuzumab and pertuzumab, without a multiagent chemotherapy backbone. Patients who had a pathologic complete response (pCR), defined as no invasive cancer in the breast or lymph nodes at surgery completed one year of trastuzumab and pertuzumab without additional chemotherapy, together with endocrine therapy and radiotherapy when indicated. Patients with residual invasive disease could receive additional adjuvant chemotherapy at the physician’s discretion,including anthracycline-based chemotherapy, followed by 14 cycles of trastuzumab emtansine (T-DM1), in accordance with the study protocol.

 Among 2,141 evaluable patients, the overall pCR rate was 43.8%¹. Higher pCR rates were associated with lower estrogen- and progesterone-receptor expression, HER2 IHC 3+ status, and weekly paclitaxel rather than docetaxel every three weeks.

HER2DX Predicts Response to a Short-Course THP Regimen

 EA1181 included a prepecified secondary analysis to determine whether the HER2DX pCR likelihood score predicted response to 12 weeks of THP independently of established clinico pathologic factors. The statistical plan was designed to detect a 30-percentage-point difference in pCR between theHER2DX pCR-high and pCR-low groups within both ER-positive and ER-negative disease. Diagnostic biopsies from 569 trial participants were centrally analyzed using the validated and standardized HER2DX test, blinded to clinical outcomes.

The pCR rate was 68.0% in the HER2DX pCR-high group versus 19.0% in the pCR-low group, an observed difference of 49 percentage points¹. The high-versus-low difference exceeded 30 percentage points in both ER-positive (58% vs 18% ) and ER-negative(70% vs 31% ) disease, and HER2DX remained independently associated with pCR after adjustment for clinico pathologic factors and type of taxane.

The EA1181 findings are supported by two additional, smaller, prospective trials in which HER2DX pCR likelihood score successfully predicted pCR following short-course THP. In DAPHNe² (n=80), pCR rates were 92.6% in theHER2DX pCR-high group versus 29.0% in the pCR-low group; in BiOnHER³(n=83), the corresponding rates were 81.8% versus 13.3%. Together, EA1181,DAPHNe, and BiOnHER evaluated HER2DX in 732 patients, consistently demonstrating its ability to distinguish tumors with high and low probabilities of achieving pCR with short-course THP.

Clinical Utility: Informing Selection for Short-Duration THP

Short-durationTHP reduces upfront chemotherapy exposure but produces lower overall pCR rates than longer, multiagent HER2-directed regimens. In a pooled analysis of 4,019 patients across 10 prospective trials⁴, pCR rates were 44.0% among 2,648 patients treated with 12 weeks of THP and 63.3% among 1,371 patients treated with six cycles of taxane and carboplatin plus trastuzumab and pertuzumab—an absolute difference of 19.3 percentage points. This illustrates an important clinical trade-off: short-duration THP results in more residual disease and, consequently, greater use of post-neoadjuvant chemotherapy andHER2-directed antibody-drug conjugates.

The clinical utility of the HER2DX pCR score is to provide additional predictive information for patients being considered for short-duration THP. By identifying tumors with high and low probabilities of achieving pCR, HER2DX can help clinicians and patients weigh the benefits of reducing upfront chemotherapy against the risk of residual disease and additional post-neoadjuvant treatment. The result complements clinico pathologic factors, physician judgment, and patient preferences.

Prospective real-world evidence further supports the clinical utility of HER2DX. In a study of 297 patients across 12 hospitals in Spain⁵, HER2DX changed physicians’ initial treatment recommendations in 48% of cases and significantly increased their confidence in those decisions. Among patients with HER2DXpCR-high tumors, pCR rates were similar with 12 weeks of a single taxane plus trastuzumab and pertuzumab compared with multiagent chemotherapy.

 “Short-duration THP can reduce upfront chemotherapy exposure, but without an effective tool to select patients, it can result in higher rates of residual disease and greater use of intensive post-neoadjuvant therapy,” said Aleix Prat, MD, PhD,co-founder of REVEAL GENOMICS and CMO. “HER2DX provides information from the diagnostic biopsy at precisely that decision point, supporting more individualized treatment decisions.”

Further evidence will come from the primary endpoint of EA1181, 3-year recurrence-free survival among patients who had a pCR after short-duration THP, and from the randomized DEFINITIVE trial (https://www.thedefinitivetrial.eu/), which is evaluating whether a HER2DX-guided strategy can reduce treatment burden without compromising efficacy.

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^{1.      Tung N, Zhao F, DeMichele A, et al. Pathologic Complete Response (pCR) Rate andPredictors of Response to Taxane, Trastuzumab, and Pertuzumab in HER2-PositiveBreast Cancer: Secondary Analyses of EA1181/CompassHER2 pCR. J Clin Oncol2026;[Epub ahead of print]. Link}

^{2.     Waks AG, Ogayo ER, Paré L, et al. Assessment of the HER2DX Assay in PatientsWith ERBB2-Positive Breast Cancer Treated With Neoadjuvant Paclitaxel,Trastuzumab, and Pertuzumab. JAMA Oncol 2023;9:835-840. Link}

^{3.     FullanaGrimalt B, Brasó-Maristany F, Petit A, et al. HER2DX genomic test inHER2-positive breast cancer treated with 15 weeks of neoadjuvant paclitaxel,trastuzumab, and pertuzumab (THP): Final analysis from the BiOnHER clinicaltrial. J Clin Oncol 2025;43(suppl 16):607. Link}

^{4.     TolaneySM, Tung N, Wolff AC, et al. HER2DX in early-stage HER2-positive breast cancer:a review of clinical utility. ESMO Open 2026;11:108345. Link}

^{5.     Martínez-Sáez O, Tapia M, Marín-Aguilera M, et al. Clinical decision impact of HER2DX, analgorithm-powered genomic diagnostic in early-stage HER2-positive breastcancer: results from a prospective real-world study. ESMO Real World Data DigitOncol 2025;8:100123. Link}

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