In the phase II PATRICIA trial reported in the Journal of Clinical Oncology, Nancy U. Lin, MD, and colleagues found that pertuzumab plus high-dose trastuzumab produced central nervous system (CNS) objective responses and clinical benefit in 68% of patients with HER2-positive metastatic breast cancer with progressive brain metastases.
As stated by the investigators, “Effective therapies are needed for the treatment of patients with HER2-positive metastatic breast cancer with brain metastases. A trastuzumab radioisotope has been shown to localize in brain metastases of patients with HER2-positive metastatic breast cancer, and intracranial xenograft models have demonstrated a dose-dependent response to trastuzumab.”
Nancy U. Lin, MD
In the U.S. multicenter trial, 39 patients with CNS metastasis progressing despite prior radiotherapy were enrolled between December 2015 and May 2017. They were treated with pertuzumab (840 mg loading dose, 420 mg every 3 weeks thereafter) and trastuzumab (6 mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity.
The primary endpoint was confirmed objective response rate in the CNS using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Clinical benefit rate was defined as the rate of complete response plus partial response plus stable disease ≥ 4 or ≥ 6 months.
At clinical cutoff (May 2019), the median duration of treatment was 4.5 months (range = 0.3–37.3 months) and median on-study duration was 16.6 months (range = 0.8–37.2 months).
Among 37 patients evaluable for efficacy, CNS objective responses (all partial) were observed in 4 patients (11%; 95% confidence interval = 3%–25%), with a median response duration of 4.6 months. Clinical benefit in the CNS was observed in 25 patients (68%) at 4 months, with a median duration of 6.6 months (range = 3.3–36.8 months), and in 19 (51%) at 6 months, with a median duration of 9.2 months (range = 3.2–36.8 months). Stable disease was ongoing for > 2 years in one patient and for > 3 years in one patient. All patients with clinical benefit in the CNS had stable or better extracranial disease.
The most common treatment-related adverse events of any grade were diarrhea (41%), fatigue (28%), and nausea (23%). Treatment-related grade 3 or 4 adverse events occurred in 8% of patients and consisted of left ventricular dysfunction, asthenia, fatigue, and hypertension (1 case each). Serious adverse events occurred in 18% of patients, with one (grade 4 hypertension) considered related to treatment. Adverse events led to discontinuation of treatment in two patients, with causes consisting of left ventricular dysfunction (treatment-related) and seizure. No fatal adverse events were reported.
The investigators concluded, “Although the CNS objective response rate was modest, 68% of patients experienced clinical benefit, and two patients had ongoing stable intracranial and extracranial disease for > 2 years. High-dose trastuzumab for HER2-positive CNS metastases may warrant further study.”
Dr. Lin, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by F. Hoffmann-La Roche/Genentech. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.