Dual Anti-HER2 Therapy Vs Trastuzumab Alone with Neoadjuvant Anthracycline and Taxane in HER2-Positive Early-Stage Breast Cancer: Real-World Insights

Baha Sharaf,1 Faris Tamimi,1 Haneen Al-Abdallat,2 Suhaib Khater,1 Osama Salama,1 Anas Zayed,1 Osama El Khatib,1 Assem Qaddoumi,1 Malek Horani,1 Yosra AL-Masri,1 Wafa Asha,1 Bayan Altalla’,1 Hira Bani Hani,1 Hikmat Abdel-Razeq1,2 1King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, The University of Jordan, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, King Hussein Cancer Center, 202 Queen Rania Al Abdullah Street P.O. Box: 1269, Amman, 11941, Jordan, Tel +962-6 5300460, Ext: 1000, Email [email protected]: The integration of anti-HER2 targeted therapy with chemotherapy has demonstrated an increase in pathologic complete response rates (pCR) in patients with HER2-positive early-stage breast cancer (EBC). This study presents real-world data on the use of trastuzumab with or without pertuzumab, in combination with anthracycline and taxanes-based chemotherapy regimen.Methods: We conducted a retrospective analysis of patients with HER2-positive EBC who underwent neoadjuvant chemotherapy (NACT), treated between January 2014 and September 2021. The regimen included four cycles of doxorubicin and cyclophosphamide (AC), followed by four cycles of docetaxel every three weeks, with anti-HER2 therapy administered alongside docetaxel. Outcomes assessed included pCR, 3-year disease-free survival (DFS), and surgical outcomes.Results: During the study period, 484 consecutive patients with HER2-positive EBC, median age of 47 (range, 21– 80) years, were enrolled. (64.7%) of patients received dual anti-HER2 therapy, while 35.3% received single-agent trastuzumab. The overall pCR rate was 44.2%, with a higher rate (55.6%) in hormone receptor (HR)-negative patients compared to HR-positive patients (39.8%), p=0.002. Although dual therapy resulted in a higher pCR rate (46.6%) compared to trastuzumab alone (39.8%), the difference was not statistically significant (p=0.15). The estimated 3-year DFS was 86.1% with dual therapy and 83.1% with trastuzumab alone (p=0.37). Further stratification revealed superior 3-year DFS in node-negative disease (96.4%) compared to node-positive disease (82.3%), p=0.0021. Patients who achieved pCR had a significantly better 3-year DFS (89.3%) compared to those with residual disease (82.2%), p=0.0177. Rate of breast conserving surgery (BCS) was lower (15.2%) among patients who received trastuzumab alone, compared to 26.5% among those who received dual anti-HER2 [Odds Ratio (OR)= 0.50, 95% Confidence Interval (CI), 0.30– 0.80, p=0.005].Conclusion: Dual anti-HER2 therapy did not significantly enhance DFS but was associated with higher BCS rates, highlighting its potential to improve surgical outcomes.Keywords: dual anti-HER2 regimen, pertuzumab, trastuzumab, breast cancer, neoadjuvant