T-DM1 shows efficacy in HER2-positive metastatic breast cancer with brain metastases
T-DMI induced clinically meaningful antitumor activity among patients with HER2-positive metastatic breast cancer and brain metastases, according to an exploratory analysis of the KAMILLA trial published in Annals of Oncology.
“Patients with brain metastases from HER2-positive breast cancer represent a difficult-to-treat population. T-DM1 has shown potential activity in this subset of patients in small clinical series,” Filippo Montemurro, MD, oncologist at the Multidisciplinary Oncology Outpatient Clinic in Torino, Italy, and colleagues wrote.
For the ongoing, international, single-arm, open-label, phase 3b KAMILLA trial, researchers sought to evaluate the safety and efficacy of the antibody-drug conjugate ado-trastuzumab emtansine (Kadcyla, Genentech), also known as T-DM1, administered at a dose of 3.6 mg/kg IV every 3 weeks among 2,002 patients with previously treated HER2-positive locally advanced or metastatic breast cancer. Treatment continued until unacceptable toxicity, withdrawal of consent or disease progression.
In the primary analysis of KAMILLA, researchers found that T-DM1 appeared well-tolerated and effective.
In the current post-hoc, exploratory analysis of the trial, Montemurro and colleagues assessed tumor response and clinical outcomes of T-DM1 among 398 patients with baseline brain metastases.
Main outcome measures included best overall response rate and clinical benefit rate according to RECIST version 1.1 criteria, PFS, OS and safety.
Among the 126 patients with measurable brain metastases, researchers reported a best ORR of 21.4% (95% CI, 14.6-29.6) and best clinical benefit rate of 42.9% (95% CI, 34.1-52).
The investigators observed a 30% or greater decrease in the sum of major diameters of brain metastases among 42.9% (95% CI, 34.1-52) of patients, including 49.3% (95% CI, 36.9-61.8) of the 67 patients who did not receive radiotherapy for brain metastases.
Median PFS among all patients with baseline brain metastases was 5.5 months (95% CI, 5.3-5.6) and median OS was 18.9 months (95% CI, 17.1-21.3).
Nervous system adverse events appeared more common among patients with baseline brain metastases (52.3% vs. 43.7%).
“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,” the researchers wrote.