Promising Combo for HER2-Positive Breast Cancer Brain Metastases

NEW YORK (Reuters Health) – In women with HER2 (ERBB2)-positive breast cancer brain metastases, combination therapy with pyrotinib and capecitabine elicited an intracranial response in a phase 2 trial.

The combination “can be a reasonable option for HER2-positive breast cancer brain metastasis with reasonable response and minimal side effects,” study coauthor Dr. Kazuaki Takabe of Roswell Park Comprehensive Cancer Center in Buffalo, New York, told Reuters Health by email.

However, he said, “This study (PERMEATE) was conducted exclusively in Chinese institutions; thus, patients were homogenously far-east Asians. The study design was single arm without a control group. The response assessment was done by each investigator.”

“The next step is to conduct a randomized control trial enrolling multiple ethnic background patients with a central review of response assessment,” he said. “Given the tolerable adverse events, a trial using multiple pan-HER receptor tyrosine kinase inhibitors should be considered.”

As reported in The Lancet Oncology, the researchers enrolled 78 women (median age, about 48) with an Eastern Cooperative Oncology Group performance status of 0-2 in a phase 2 trial that is ongoing in eight tertiary-care hospitals in China.

Fifty-one patients (86%) had radiotherapy-naive HER-2-positive brain metastases (cohort A) and the rest had progressive disease after radiotherapy (cohort B). All received pyrotinib 400 mg orally once daily, and capecitabine 1,000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until disease progression or unacceptable toxicity.

The primary endpoint was the rate of confirmed intracranial objective responses.

After a median follow-up of 15.7 months, the intracranial objective response rate was 74.6% in cohort A and 42.1% in cohort B.

The most common grade 3 or worse treatment-emergent adverse event was diarrhea (24% in cohort A and 21% in cohort B). Treatment-related serious adverse events occurred in two patients (3%) in cohort A and three (16%) in cohort B. No treatment-related deaths occurred.

The authors conclude, “To our knowledge, this is the first prospective study showing the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in a radiotherapy-naive population. This combination deserves further validation in a randomized, controlled trial.”

Dr. Thomas Bachelot of the Unicancer National Breast Cancer Group – UCBG in Lyon, coauthor of a related editorial, highlighted key points for clinicians and researchers in an email to Reuters Health:

– Few published studies have specifically addressed treatment for active breast cancer brain metastases, and those that did contained an HER2 tyrosine-kinase inhibitor, usually in combination with capecitabine, because the inhibitor is thought to be better able to cross the blood-brain barrier than a monoclonal antibody.

– Results of the current study are consistent with previous studies.

– Large molecules such as trastuzumab emtansine can also be active in brain metastases, and evidence of trastuzumab deruxtecan activity in active brain metastases is also emerging.

– Therefore, the intrinsic efficacy of a particular treatment, rather than whether or not it can cross the blood-brain barrier, seems to be the main driver of brain metastases activity, since the blood-brain barrier is mostly disrupted in breast cancer brain metastases.

“More prospective studies with precise clinical activity data are needed,” he concluded.

The study was funded in part by Jiangsu Hengrui Pharmaceuticals.

SOURCE: https://bit.ly/3GR0Ck8 and https://bit.ly/3HLTC9k The Lancet Oncology, online January 24, 2022.

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