Abstract

Abstract Background: Clinical practice guidelines recommend the combination of pertuzumab (PERJETA®), trastuzumab (Herceptin®) (PH) and a taxane for first-line treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer (HER2+ mBC) patients [Giordano et al., J Oncol Pract, 2018]. Most clinical trials investigating the efficacy and safety of pertuzumab and trastuzumab used docetaxel as the taxane (PHD) [Tian et al., Int J Clin Pharmacol Ther, 2017]. Paclitaxel used with pertuzumab and trastuzumab (PHP) is highly active and well tolerated and may be an effective alternative to docetaxel-based combination therapy (Bachelot et al., Ann Oncol, 2019; Dang et al., J Clin Oncol, 2017). We evaluated the use of taxanes with PH and patient outcomes after receiving PHP or PHD as first-line treatment for HER2+ mBC in a real-world setting. Methods: We conducted a retrospective cohort study, using the nationwide Flatiron Health Electronic Health Record (EHR)-derived de-identified database. Patients who received a taxane with PH as initial systemic therapy after mBC diagnosis between June 1, 2012 and April 30, 2019 were included. The taxane initiation and any switch was evaluated. An intention-to-treat analysis was adopted and we used Cox-proportional hazard model in the statistical analysis. Time To Last Administration (TTLA) was used as a proxy for treatment duration for PH and chemotherapy. Real world progression free survival (rwPFS) was used to describe the effectiveness of first-line therapies. Results: A total of 1054 patients received PH plus a taxane as first-line therapy for HER2+ mBC: 29.3% of patients received PHP (26.9% paclitaxel and 2.4% nab-paclitaxel) while 70.7% of patients received PHD. Patients in the PHP group at index date were significantly older (median age was 62.0 in PHP vs 58.0 in PHD group, <0.001), more likely to be recurrent patients (51.8% in PHP vs 44.3% in PHD, 0.032) and less frequently treated in the community setting (86.7% in PHP vs 96.4% in PHD, <0.001). Fifty-four (5.1%) patients switched taxane during first-line therapy. Fifteen (5.3%) switched from paclitaxel to nab-paclitaxel, 39 (5.2%) switched from docetaxel to either paclitaxel or nab-paclitaxel. No patient switched from paclitaxel or nab-paclitaxel to docetaxel. Median TTLA of the index taxane was 3.7 months (3.42, 3.91) in PHP vs 3.5 months (3.45, 3.45) in PHD. Median TTLA of PH was 10.6 months (95% CI 8.51-11.8) for PHP and 11.8 months (95% CI 10.49-13.3) for PHD. Median rwPFS was 12.9 months (95% CI 11.2, 15.8) for PHP and 14.9 months (95% CI 13.2-16.9) for PHD. No statistically significant difference was found between PHP and PHD for TTLA of PH and for rwPFS either in the unadjusted models or in the models adjusted for potential confounders. Conclusion: To our knowledge, this is the first study addressing the real world use of paclitaxel and evaluating the effectiveness of PHP vs PHD as first-line treatment in HER2+ mBC patients. PHP is used in the community practice and appears as effective as PHD. Citation Format: Letizia Polito, Jinjoo Shim, Yolande Du Toit, Thy Do, Adam Knott, Thibaut Sanglier. Use of pertuzumab in combination with taxanes for HER2+ metastatic breast cancer: Analysis of U.S. electronic health records [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-14.

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