KAMILLA findings support T-DM1 for HER2-positive breast cancer brain metastases
medwireNews: Exploratory analyses from the KAMILLA trial indicate that trastuzumab emtansine (T-DM1) may be a feasible option for HER2-positive breast cancer patients who have brain metastases (BM).
The primary results from the ongoing phase 3b study pointed to T-DM1 being well tolerated and active for the full study population of patients who had progressed after chemotherapy and HER2-directed therapy, explain Filippo Montemurro, from Candiolo Cancer Institute in Torino, Italy, and co-workers.
To investigate further, the team collated information for the 398 participants who had BM at baseline and were given T-DM1 3.6 mg/kg at 3-week intervals until unacceptable toxicity, disease progression, or withdrawal of consent.
Overall, 7.9% of the 126 patients with measurable target lesions had received brain radiation within 30 days of beginning T-DM1 therapy, 38.9% received brain radiation at least 30 days before T-DM1 treatment (median 8.4 months), and 53.2% did not receive brain radiation.
The best overall response rate – defined as a complete or partial response – was 21.4% for the patients with measurable brain metastases, and an additional 21.4% achieved stable disease for at least 6 months, giving a clinical benefit rate of 42.9%.
“These figures can be considered clinically relevant in this heavily pretreated population,” write Montemurro et al in the Annals of Oncology.
In addition, 42.9% of patients had a 30% or greater reduction in the sum of the major diameters of brain metastases, including 49.3% of those who had not previously received brain radiation.
“As this is unbiased by prior radiotherapy or other forms of local therapy to the brain, it represents the direct therapeutic effect of T-DM1 in BM,” the researchers remark, adding that further research is warranted to determine if this is associated with neurologic benefits.
Among the whole population of patients with brain metastases, the median progression-free survival and overall survival were 5.5 and 18.9 months, respectively.
The authors describe adverse events as being “broadly similar in patients with and without baseline BM” except for a greater rate of nervous system side effects in the brain metastases cohort, affecting 52.3% and 43.7%, respectively.
Specifically patients with versus without baseline BM were at least 1% more likely to have serious adverse events of epilepsy, seizure, and brain edema, while grade 3 or more severe central nervous system (CNS) hemorrhage occurred in four and two patients, respectively.
The author of an accompanying editorial writes that “[t]his study solidifies the clinical evidence supporting CNS activity of T-DM1 in patients with HER2-positive breast cancer brain metastases.”
Nancy Lin, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, observes that trials are now ongoing to determine whether a HER2-targeted tyrosine kinase inhibitor can augment the activity of T-DM1.
But noting that this is the first study of CNS activity in the 7 years since T-DM1 was approved as a treatment, she laments that the studies of subsequent antibody–drug conjugates (ADCs) have continued to exclude patients with BM and lack information on CNS activity, representing “a missed opportunity to address an unmet medical need.”
The editorialist therefore concludes that “this and other published literature strongly support the exploration of additional ADCs in the treatment of patients with active brain metastases, in breast and other malignancies.”
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