Abstract PO4-01-03: Dual anti-HER2 Therapy with Pertuzumab and Trastuzumab versus Trastuzumab Alone in Addition to Anthracycline and Taxane-Based Neoadjuvant Therapy in Patients with HER2-Positive Early-Stage Breast Cancer; Real-World Data
Authors: Baha' Sharaf, Faris Tamimi, Osama Salama, Anas Zayed, Osama El Khatib, Suhaib Khater, Malek Horani, Suhaib Al-Sawajneh, Yosra AL-Masri, Hikmat Abdel-Razeq
Journal: Cancer Research (2024)

Abstract Background: When use in the neoadjuvant setting, anti-HER2 targeted therapy had improved pathologic complete response rate (pCR) in patients with HER2-positive early-stage breast cancer (EBC). Here we present real-world data on the use trastuzumab with or without pertuzumab on the backbone of anthracycline and taxanes-based NSAPB-B27 chemotherapy regimen. Methods: We retrospectively reviewed records of patients with HER2-positive EBC who received neoadjuvant therapy using the National Surgical Adjuvant Breast and Bowel Project (NSABP)-B27 protocol (4 cycles of adriamycin and cyclophosphamide, followed by 4 more cycles of docetaxel; all given every 3 weeks) with anti-HER2 therapy from Jan 2014 to September 2021, treated at a tertiary care cancer center. The clinicopathological features, treatment received, and outcome were collected from patients’ electronic medical records. We estimated 3-year disease-free survival (DFS), a validated endpoint in HER2-positive EBC, using Kaplan-Meier with recurrence and/or death as events. Outcomes were reported in subgroups based on known prognostic factors. Results: The study comprised 528 patients with a median follow-up of 36 months. Median age was 48 (21-80) years. Hormone receptors (HR) were positive in 379 (71.8%), lymph node-involvement prior to neoadjuvant therapy was reported in 402 (76.1%) patients and 319 (60,4%) had grade-3 disease. Majority (n= 482, 91.3%) were labeled HER2-positive based on immunohistochemistry staining (IHC+3) and the rest were based on IHC+2 with positive FISH/ISH. Dual anti-HER2 therapy (trastuzumab and pertuzumab) was used in 316 (59.8%) patients, single agent trastuzumab in 173 (32.8 %) patients, while 39 (7.4%) others did not receive any anti-HER2 therapy. Except for 9 (1.7%) patients who progressed while on treatment, all patients underwent surgery. Among the whole group, 225 (43.4%) achieved pCR; significantly higher (n=80, 53.7%) in HR-negative compared to 38.3% among those with HR-positive disease, p=0.002. Additionally, pCR was higher in patients who received dual anti-HER2 (46.2%) compared to 39.3% for those treated with trastuzumab and 28.2% for those who did not receive anti-HER2 therapy. Following surgery, 463 (89.4%) of the patients received adjuvant trastuzumab, however, none of them received pertuzumab or TDM1 in adjuvant sitting. Estimated 3-year DFS was 86.1% with dual anti-HER2 and 83.0% with trastuzumab alone, p=0.19. However, DFS was better among those with node-negative disease; 96.5% compared to 80.9% in node-positive disease, p= &amp;lt; 0.001. Patients who achieved pCR had significantly better 3-year DFS; 89.3% compared to 80.2% in patients with residual disease, p= 0.006. Conclusions: Even with the wide use of pertuzumab in the neoadjuvant setting, the DFS was not improved compared to trastuzumab alone, and this highlights the importance of switching trastuzumab to TDM1, or to continue with pertuzumab in the adjuvant setting in patient with residual disease. Citation Format: Baha' Sharaf, Faris Tamimi, Osama Salama, Anas Zayed, Osama El Khatib, Suhaib Khater, Malek Horani, Suhaib Al-Sawajneh, Yosra AL-Masri, Hikmat Abdel-Razeq. Dual anti-HER2 Therapy with Pertuzumab and Trastuzumab versus Trastuzumab Alone in Addition to Anthracycline and Taxane-Based Neoadjuvant Therapy in Patients with HER2-Positive Early-Stage Breast Cancer; Real-World Data [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-03.