Background: The addition of pertuzumab to trastuzumab for patients (pts) with HER2 +ve breast cancer results in higher rates of pathological complete response (pCR);although, it is not yet known if this translates into improved survival outcomes. In May 2016 pertuzumab was approved in Australia by the Therapeutic Goods Administration, in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of locally advanced and inflammatory HER2+ve breast cancer; and in September 2018, for early stage (>2cm diameter or node positive) disease. This study aims to capture real world data on the safety and effectiveness of pertuzumab in the neoadjuvant setting.
Methods: PeRSIA (ML39622) is a secondary data use non-interventional study of pts initiating or considering pertuzumab treatment in the neoadjuvant setting for non-metastatic HER2+ breast cancer. The primary objective is to assess the incidence rates of all adverse events (AEs) related to pertuzumab and the effectiveness of neoadjuvant pertuzumab when added to trastuzumab, in the real world setting. De-identified data obtained from the pts’ medical notes by the treating physician, were deposited to a centralized data capture tool (REDCaP), hosted at the Walter and Eliza Hall Institute of Medical Research. This interim analysis reports the co-primary endpoints of breast pCR (bpCR) with or without in situ disease (ypT0/is or ypT0), total pCR with or without in situ disease (ypT0/is ypN0 or ypT0 ypN0), and the incidence of AEs related to pertuzumab. Secondary objectives include rates of breast or nodal surgery, relapse free survival (RFS) and overall survival (OS).
Results: Ninety pts receiving neoadjuvant pertuzumab were enrolled for data capture between March 2018 and June 2019. Sixty-nine of these pts had data available for interim analysis by June 18th 2019 (Table). HER2-targeted neoadjuvant treatment was completed in 65/69 pts (94.2%) with a median [min-max] duration of 4 [1-6] cycles of pertuzumab and 5 [1-6] cycles of trastuzumab, and chemotherapy was administered in all 69 pts. The most common neoadjuvant chemotherapy regimens were taxanes + anthracyclines (n=30, 43.5%) and single agent taxane (n=26, 37.7%). Surgery was performed in 66/69 pts (95.7%). The bpCR was 71.2% and the total pCR rate was 66.7%. All pts who did not achieve a pCR obtained a partial response (28.8%). Total pCR was achieved by 20/26 (76.9%) hormone receptor-negative and 24/40 (60.0%) hormone receptor-positive pts. Three pts (4.3%) experienced at least one pertuzumab-related AE [cardiac toxicity (n=1, 1.4%), diarrhea (n=2, 2.9%), rash (n=1, 1.4%) and (sepsis n=1, 1.4%)] and all ceased pertuzumab. RFS and OS were 97.1% and 98.6% respectively, with a median follow up time from diagnosis of 16.1 [4-36.4] months. One patient did not undergo surgery due to a new non-breast cancer which resulted in death.
Conclusion: This is the first multicenter, prospective, observational study to report pCR with pertuzumab in real world clinical practice in Australia. Neoadjuvant therapy based on dual blockade with pertuzumab and trastuzumab for HER2+ non metastatic breast cancer achieved a total pCR rate of 66.7% and bpCR rate of 71.2%, which was numerically higher than previously reported in clinical trials. There were no significant safety findings outside of the accepted safety profile for pertuzumab.
Acknowledgment: Study sponsored by Roche Products, Pty. Limited
Table: Patient and Tumor CharacteristicsCharacteristicNumber (%)Age51.8 (25.9-82.1)Charlson Comorbidity Index058 (84.1)18 (11.6)≥23 (4.4)Tumor Size (Clinical/Radiological staging)T1 (<2 cm)9 (13)T2 (2-5 cm)44 (63.8)T3 (>5 cm)14 (20.3)Unknown2 (2.9)Tumor Grade10 (0)220 (29.0)347 (68.1)Unknown2 (2.9)Nodal Status (Clinical/Radiological)Node positive46 (66.7)Node negative23 (33.3)Hormone Receptor StatusHR+42 (60.9)HR−27 (39.1)Median baseline left ventricular ejection fraction65%Patient cardiac risk factorsNo risk factor40 (58.0)1 risk factor14 (20.3)≥2 risk factors15 (21.7)
Citation Format: Sheau Wen Lok, Richard De Boer, Sally Baron-Hay, Fran Boyle, Peter Button, Belinda Castles, Bianca Devitt, Peter Fox, Michael Harold, Ganessan Kichenadasse, Belinda E Kiely, Gavin Marx, Louise Nott, Laura Pellegrini, Ali Tafreshi, Peter Gibbs. Pertuzumab study for HER2-positive non-metastatic breast cancer in the neoadjuvant setting in Australia: Interim analysis [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 P1-18-15.
