ADC With Radiotherapy for Brain Mets Ups Risk of Necrosis

TOPLINE:

For patients with brain metastases, treatment with an antibody-drug conjugate (ADC) at the same time as stereotactic radiotherapy significantly raises the risk of symptomatic radiation necrosis, a new retrospective study suggests.

METHODOLOGY:

Stereotactic radiotherapy is a key treatment for patients with brain metastases, but some develop radiation necrosis. Because ADCs can help shrink brain metastases as well, the researchers wanted to see whether adding an ADC to stereotactic radiotherapy increased patients’ risk of symptomatic radiation necrosis.
The study included 98 patients (84% women; median age, 55) with brain metastases who received at least one course of stereotactic radiotherapy for intact brain metastases and at least one dose of trastuzumab emtansine, trastuzumab deruxtecan, or sacituzumab govitecan.
Stereotactic radiotherapy was considered concurrent with ADC therapy if delivered within 7 days before the ADC or within 21 days after the ADC. The control cohort included patients with brain metastases treated sequentially with stereotactic radiotherapy and an ADC.
Symptomatic radiation necrosis was the primary outcome, and the researchers used competing risks regression models to analyze the impact of concurrent therapy.

TAKEAWAY:

For the entire cohort, the 24-month cumulative incidence of symptomatic radiation necrosis was 8.5%. ADC therapy given concurrently with stereotactic radiotherapy was associated with higher risk for symptomatic radiation necrosis in univariable analysis (subdistribution hazard ratio [SHR], 4.01) and multivariable analysis (SHR, 4.31) that controlled for prior radiotherapy and volume of brain metastases.
The risk of symptomatic radiation necrosis with concurrent ADC was modest for patients with small brain metastases who received a first course of stereotactic radiotherapy but was substantial for those with larger and re-irradiated lesions treated with concurrent ADC.
For previously radiated lesions, the 24-month risk of necrosis was 42% with concurrent ADC, vs 9.4% without concurrent ADC.
Grade 4 to 5 symptomatic radiation necrosis following stereotactic radiotherapy was observed in 7.1% of brain metastases treated with concurrent ADC, vs 0.7% treated without concurrent ADC. There was no difference in risk between different ADC agents.

IN PRACTICE:

On the basis of current findings, the researchers concluded that “clinicians should be cognizant of the [symptomatic radiation necrosis] risk and monitor patients closely when treating concurrently with ADCs.”

SOURCE:

The study, with first author Emily S. Lebow, MD, of Memorial Sloan Kettering Cancer Center in New York, was published online October 26 in JAMA Oncology.

LIMITATIONS:

Limitations include the retrospective study design as well as uncertainty in discriminating between radiation necrosis and local treatment failure.

DISCLOSURES:

The study had no specific funding. Four of the six authors reported various relationships with industry.

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