One reason is studies of new drugs typically exclude concurrent radiotherapy, said Kathy Miller, MD, a contributor to this news organization and professor of oncology and medicine at the Indiana University School of Medicine, Indianapolis, Indiana.
If trials evaluating new targeted therapies included concurrent radiotherapy, it would be challenging to identify whether toxicities came from the drug itself, the radiation, or the combination, Dr. Miller explained.
Given the limited evidence, “we tend to be cautious and conservative” and not combine therapies that “we don’t know are safe or appropriate for patients,” said Chirag Shah, MD, director of breast radiology at the Cleveland Clinic, Cleveland, Ohio.
Below is a guide to what we do and don’t know about combining radiotherapy and systemic treatments in breast cancer.
1. Immunotherapy plus radiotherapy likely safe but evidence is limited
Safety data on combining immune checkpoint inhibitors and radiotherapy in breast cancer are limited because concurrent radiotherapy has typically been excluded in pivotal trials.
The 2020 KEYNOTE-522 trial did provide a rare look at concurrent radiotherapy and immunotherapy in early triple-negative breast cancer. The analysis found “no safety concerns” with concurrent radiotherapy and pembrolizumab, lead investigator Peter Schmid, MD, of Queen Mary University of London, England, told this news organization.
Research on other solid tumor types also suggests that radiotherapy “can be considered safe” alongside immunotherapy, the authors of a recent ESTRO consensus said.
Despite evidence indicating radiotherapy alongside immunotherapy can be safe in patients with breast cancer, “certain aspects, such as patient selection, total dose, and dose per fraction, remain open for debate to achieve the best therapeutic outcomes,” the ESTRO experts cautioned.
2. CDK4/6 inhibitors may be offered with radiotherapy in some settings, not others
CDK4/6 inhibitors are now standard of care for first- or second-line treatment in patients with advanced or metastatic hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer.
“Unfortunately, we found no information regarding concurrent radiotherapy in the adjuvant setting” in pivotal trials for palbociclib, abemaciclib, and ribociclib, the ESTRO authors said. In the pivotal trials for palbociclib and abemaciclib, patients had to discontinue immunotherapy before initiating radiotherapy, and in the trial for ribociclib, palliative radiotherapy was allowed for relieving bone pain only.
However, in 2023, a team of experts from 12 countries attempted to piece together the available evidence, publishing a meta-analysis of 11 retrospective studies on the safety of CDK4/6 inhibitors given concurrently with radiotherapy in patients with metastatic disease.
Although most of these studies had small patient populations, the analysis revealed that CDK4/6 inhibitors given concurrently with radiotherapy in patients with metastatic breast cancer led to a similar side-effect profile to that observed in trials of the inhibitors given sequentially with adjuvant radiotherapy.
“These findings suggest that the simultaneous administration of CDK4/6 inhibitors and radiotherapy is generally well tolerated,” the ESTRO authors concluded but added that CDK4/6 inhibitors and concomitant radiotherapy should be investigated more in the adjuvant locoregional, whole brain, and intracranial stereotactic radiotherapy settings.
The expert panel did note, however, that CDK4/6 inhibitors and concomitant radiotherapy “could be offered” during palliative and ablative extracranial radiotherapy.