Abstract P2-13-38: Pertuzumab study for HER2-positive non-metastatic breast cancer in the neoadjuvant setting in Australia
Authors: Lok Sheau Wen , De Boer Richard , Baron-Hay Sallt , Button Peter , Devitt Bianca , Forster Benjamin , Fox Peter , Harold Michael , Ketheeswaran Sahisha , Kichenadasse Ganessan , Kiely Belinda E , Marx Gavin , Nott Louise , Pellegrini Laura , Tafreshi Ali , GIbbs Peter 
Published: March 2022

BACKGROUND Adding pertuzumab to trastuzumab in patients (pts) with HER2+ breast cancer improves pathological complete response (pCR) rates. Pertuzumab + trastuzumab + chemotherapy is approved in Australia as neoadjuvant therapy in early stage (&gt;2 cm or node positive), locally advanced and inflammatory HER2+ breast cancer. This study captured 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 neoadjuvant pertuzumab treatment for non-metastatic HER2+ breast cancer. The primary objective is to assess the effectiveness and safety of neoadjuvant pertuzumab when added to trastuzumab in the real-world setting. Deidentified data obtained from the pts’ medical notes were captured using REDCaP, hosted at the Walter and Eliza Hall Institute of Medical Research. This analysis reports the co-primary endpoints of breast pCR (bpCR) with or without in situ disease (ypT0/is or ypT0), total pCR (tpCR) with or without in situ disease (ypT0/is ypN0 or ypT0 ypN0), and the incidence of adverse events (AEs) related to pertuzumab. Secondary objectives include describing rates of breast and nodal surgery, relapse free survival (RFS) and overall survival (OS). RESULTS Ninety five pts receiving neoadjuvant pertuzumab were enrolled between March 2018 and July 2019, with data available for all pts. HER2-targeted neoadjuvant treatment was completed in 91 pts (95.8%) with a median number of 4 cycles [range 1-6] of pertuzumab and 5 cycles [range 1-6] of trastuzumab. Four pts did not complete the planned neoadjuvant therapy due to early CR (n=1), and pertuzumab-related AEs (n=3). The most common neoadjuvant chemotherapy regimens were sequential anthracyclines + taxanes (n=59, 62.1%) and single agent taxane (n=29, 30.5%). Surgery was performed in 92 pts (96.8%). Three pts did not proceed to surgery due to patient decision (n=1), physician decision (n=1), and development of a new non-breast cancer which resulted in death (n=1). Of those pts that underwent surgery, 65/92 (70.7%) had a bpCR and 59/92 (64.1%) had a tpCR. All pts who did not achieve a pCR obtained a partial response (33/92, 35.9%). Total pCR was seen in 27/34 (79.4%) pts with hormone receptor-negative and 32/58 (55.2%) pts with hormone receptor-positive cancers. 27/95 (28.4%) pts experienced an AE related to pertuzumab; diarrhea (21.1%) and rash (4.2%) were the most common AEs. Three pts (3.2%) discontinued pertuzumab due to an AE: cardiac toxicity, diarrhea and rash (n=1), cardiac toxicity (n=1), and diarrhea and sepsis (n=1). Following surgery, 93/95 (97.9%) patients received adjuvant HER2-directed therapy, and 4/95 (4.2%) received adjuvant chemotherapy. After a median follow-up from diagnosis of 21.2 [14.0-83.9] months, the RFS and OS were 92.6% and 99.0% respectively. Disease recurrence occurred in 6 pts (distant n=4, contralateral n=2). CONCLUSIONS This is the first multicenter, observational study of neoadjuvant therapy based on dual blockade with pertuzumab and trastuzumab for HER2+ non-metastatic breast cancer in Australia. The pCR rates achieved were numerically higher than previously reported in clinical trials. There were no significant safety findings outside of the expected safety profile for pertuzumab. Acknowledgments: Study sponsored by Roche Products, Pty. Limited. Theresa Wade (WriteSource Medical) provided medical writing.

Table: Baseline Characteristics (n=95)CharacteristicNumber (%)Age, median (range)50.3 (24.4 -82.1)Charlson Comorbidity Index- 077 (81.1)- 19 (9.5)- 2 +9 (9.5)Tumour Size12 (12.6)- T156 (59.0)- T225 (26.3)- T3- Unreported2 (2.1)Tumour Grade- 10 (0)- 231 (32.6)- 362 (65.3)- Unreported2 (2.1)Nodal status- Positive63 (66.3)- Negative32 (33.7)Hormone Receptor Status- HR+60 (63.2)- HR-35 (36.8)Median baseline left ventricular ejection fraction (range)65.0% (35-79)Cardiac risk factors- 053 (55.8)- 122 (23.2)- 2+20 (21.1)

Citation Format: Sheau Wen Lok, Richard De Boer, Sallt Baron-Hay, Peter Button, Bianca Devitt, Benjamin Forster, Peter Fox, Michael Harold, Sahisha Ketheeswaran, 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 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-38.