ASCO: Breast Cancer Brain Mets Treated with Tucatinib

The risk of death or progression of brain metastases was reduced if patients with breast cancer added tucatinib (Tukysa) to a regimen of trastuzumab and capecitabine, researchers reported at the virtual annual meeting of the American Society of Clinical Oncology.

Patients who were treated with trastuzmab and capecitabine alone achieved a median overall survival of 12.0 months, but that survival was increased to 18.1 months with tucatinib on board (P=0.005), reported Nancy Lin, MD, associate professor of medicine at Dana-Farber Cancer Institute/Harvard Medical School, Boston.

In her oral presentation, and in her paper that was published simultaneously in the Journal of Clinical Oncology, Lin also reported that the median central nervous system progression-free survival was 9.9 months in the tucatinib-treated patients compared with 4.2 months among the patients getting trastuzmab and capecitabine alone (P=0.03).

She said that the combined primary endpoint of death or progression of brain metastases was a 68% reduction in favor of tucatinib (P<0.0001).

The results of the HER2CLIMB study, which specifically studied intracranial objective responses, found that responses were observed in 47.3% of the patients on tucatinib compared with 20% of the patients on trastuzumab/capecitabine (P=0.03). In addition, Lin said that at one year, 70% of patients randomized to tucatinib were alive compared to 47% of patients randomized to the placebo arm of the study.

In commenting on the results of HER2CLIMB, the designated discussant, Aleix Prat, MD, PhD, head of medical oncology at the Hospital Clinic of the University of Barcelona, Spain, noted that the last decade has shown major improvements in survival among breast cancer patients with advanced disease “But we still have work to do,” he said, particularly when it comes to treating brain metastases.

“Today we’ve seen the results of tucatinib in patients with brain metastases,” he said. “These were patients recruited in the HER2CLIMB, which is a randomized double-blind pivotal trial of patients with HER2-positive advanced disease who received prior trastuzumab/pertuzumab and T-DM1 and who had a brain MRI at baseline. About 48% of patient had brain metastases at baseline, and that among them, 60% had active brain metastases, meaning untreated brain metastases or progressing brain metastases.

“The results in patients with central nervous system disease look very similar to the results in the general population of HER2CLIMB. In terms of response, it was 47% compared to 41% in the general population; in terms of median progression-free survival, it was 7.6 months compared to 7.8 months in the general population. And in terms of overall survival it was 18.1 months compared with 22 months in the general population,” Prat said in his pre-recorded comments.

The investigators scrutinized progression free survival in central nervous system disease only. In that subset of patients, the risk of progression was reduced 68%, with “an absolute increase in progression-free survival of 5.4 months. So overall, very impressive results of tucatinib in patients with central nervous system disease,” he said.

Prat suggested that future studies might try to determine if treatment with tucatinib can be used upfront in treatment as a preventive agent.

In her report, Lin noted, “Up to 50% of patients with human epidermal growth factor receptor 2 (HER2) — positive metastatic breast cancer will develop brain metastases during the course of their disease. Initial therapy for brain metastases typically consists of locally directed therapy with surgical resection, stereotactic radiosurgery, and/or whole-brain radiation therapy. Unfortunately, the rate of intracranial progression within 6 to 12 months with these therapies is high.

“In the absence of randomized, prospective data demonstrating a benefit of switching systemic agents at the time of brain progression, ASCO clinical practice guidelines currently recommend that patients with stable systemic disease at the time of brain progression continue treatment with the same systemic treatment after local therapy and until further progression,” she added.

In the subset of patients that comprised the current trial report, brain MRI was required every 6 weeks for the first 24 weeks and every 9 weeks thereafter. Eligible patients did not require immediate local therapy for their central nervous system lesions. The median age was just over 50; 99% of the patients were women. All the patients were EGOG performance status of 0-1. Forty percent of patients initially presented with de novo metastatic breast cancer. Lin said 97% of the patients has co-existing extracranial disease; 70% of patients had received prior radiotherapy and 14%-16% had previously been treated with central nervous system directed surgery.

Samuel Kailes, Contributing Writer, BreakingMED™

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