Pertuzumab plus high-dose trastuzumab for HER2-positive breast cancer with brain metastases: PATRICIA final efficacy data

Nancy U Lin; Priya Kumthekar; Solmaz Sahebjam; Nuhad Ibrahim; Anita Fung; Anna Cheng; Alan Nicholas; Jesse Sussell; Mark Pegram

doi:10.1038/s41523-023-00587-2

Pertuzumab plus high-dose trastuzumab for HER2-positive breast cancer with brain metastases: PATRICIA final efficacy data

NPJ Breast Cancer. 2023 Nov 17;9(1):94. doi: 10.1038/s41523-023-00587-2.

Authors

Nancy U Lin^#¹, Priya Kumthekar^#², Solmaz Sahebjam^{3

4}, Nuhad Ibrahim⁵, Anita Fung⁶, Anna Cheng⁶, Alan Nicholas⁶, Jesse Sussell⁶, Mark Pegram⁷

Affiliations

¹ Dana-Farber Cancer Institute, Boston, MA, USA. nancy_lin@dfci.harvard.edu.
² Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
³ Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
⁴ Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁵ MD Anderson Cancer Center, Houston, TX, USA.
⁶ Genentech Inc., South San Francisco, CA, USA.
⁷ Stanford Comprehensive Cancer Institute, Palo Alto, CA, USA.

^# Contributed equally.

Abstract

The PATRICIA study (NCT02536339) examined the efficacy and safety of pertuzumab plus high-dose trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) with progressive central nervous system (CNS) metastases following radiotherapy. Primary analysis confirmed CNS objective response rate (ORR) was 11% (95% confidence interval [CI]: 3-25); clinical benefit rate (CBR) was 68% (4 months) and 51% (6 months). We report final efficacy data after a further 21-months of follow-up, updated safety, survival, and patient-reported outcomes (PROs). Patients received standard-dose pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. Primary endpoint: confirmed ORR (CNS) per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary endpoints were response duration, CBR, progression-free survival (PFS), overall survival (OS), safety, and PROs. By clinical cut-off, 39 patients had completed or discontinued treatment. Confirmed ORR (CNS) was 11% (95% CI: 3.0-25.4). Median CNS-PFS was 4.6 months (95% CI: 4.0-8.9), as was median CNS-PFS or systemic PFS (95% CI: 4.0-8.9); median OS was 27.2 months (95% CI: 16.1-not reached). CBR in the CNS was 51% (19 patients, 95% CI: 34.4-68.1) at 6 months. Two patients remained on treatment until study closure, achieving stable disease for 4.1 and 4.8 years. Treatment-related grade 3/4 adverse events occurred in 7.7% of patients. Patients with confirmed partial response or stable disease (≥4 months) in the CNS had stable PROs over time. Pertuzumab plus high-dose trastuzumab represents a reasonable non-chemotherapeutic treatment option for selected patients with HER2-positive MBC with CNS metastases.