An exploratory subgroup analysis of the KAMILLA trial represents the largest reported cohort of patients with HER2-positive breast cancer and brain metastases treated with the anti-HER2 antibody-drug conjugate ado-trastuzumab emtansine, or T-DM1, in a prospective setting. Researchers observed clinically meaningful antitumor activity in patients who had and had not undergone prior radiotherapy. The findings by Montemurro et al were published in Annals of Oncology.
Systemic treatment with HER2-targeted agents may improve clinical outcomes in patients with HER2-positive metastatic breast cancer and brain metastases. Activity of the HER2-targeted tyrosine kinase inhibitors lapatinib and neratinib alone or in combination with capecitabine, and the HER2-specific tyrosine kinase inhibitor tucatinib in combination with trastuzumab and capecitabine, has been reported in patients with HER2-positive metastatic breast cancer and brain metastases.
“This exploratory analysis of patients with HER2-positive metastatic breast cancer and brain metastases enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting.”— Montemurro et al
Tweet this quote
The authors wrote in the study background that among other potentially active drugs in these patients, T-DM1 has been shown to improve overall survival in patients with trastuzumab-resistant advanced metastatic breast cancer and asymptomatic brain metastases previously treated with radiotherapy, compared with lapatinib plus capecitabine. Two small additional studies also provided signals of T-DM1 clinical activity in this difficult-to-treat population.
KAMILLA is an ongoing, international, single-arm, open-label, phase IIIb study evaluating the safety and efficacy of T-DM1 in patients previously treated with HER2-targeted therapy and chemotherapy for HER2-positive locally advanced or metastatic breast cancer. The primary analysis found that T-DM1 was well-tolerated and showed efficacy consistent with that reported in previous studies. In the new paper, the research team now reports the results of a post hoc exploratory analysis describing T-DM1 safety and efficacy in patients with and without baseline brain metastases based on final cohort 1 data.
Patients received T-DM1 until unacceptable toxicity, withdrawal of consent, or disease progression. The main outcome measures were best overall response rate (defined as complete response plus partial response) and clinical benefit rate (defined as complete response plus partial response plus stable disease lasting ≥ 6 months) as determined by Response Evaluation Criteria in Solid Tumors version 1.1, progression-free survival, overall survival, and safety.
Among 2,002 treated patients, 398 had baseline brain metastases. In 126 patients with measurable brain metastases, the best overall response rate was 21.4% (95% confidence interval [CI] = 14.6%–29.6%) and the clinical benefit rate was 42.9% (95% CI = 34.1%–52.0%).
A reduction in the sum of the major diameters of brain metastases ≥ 30% occurred in 42.9% of patients (95% CI = 34.1%–52.0%), including 49.3% (95% CI = 36.9%–61.8%) of 67 patients who had not undergone prior radiotherapy for brain metastases.
In the 398 patients with baseline brain metastases, median progression-free survival was 5.5 months (95% CI = 5.3–5.6) and overall survival was 18.9 months (95% CI = 17.1–21.3).
The adverse events profile was similar in patients with and without baseline brain metastases, although central nervous system adverse events were more common in patients with baseline metastases.
The study authors concluded, “This exploratory analysis of patients with HER2-positive metastatic breast cancer and brain metastases enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting.”
Disclosure: For full disclosures of the study authors, visit annalsofoncology.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®.