Do you recommend holding a KRAS inhibitor during palliative radiotherapy?

I have no personal experience or anecdotes and know of no current data or literature that would address this very specific question and this may be due to the limited experience on the potential interaction of this class of drugs and radiotherapy, since this drug is relatively new.

This class of drug is reported (in the lab) to have radiosensitizing effects (Cuneo et al., PMID 30412912). Also, in the drug information provided by Amgen on sotorasib [the drug recently approved for use in metastatic...

I generally hold since palliative RT is limited to a few days to avoid concerns about potential enhanced toxicity. Nonetheless, sotorasib was given concurrently with locoregional therapies such as RT in some patients including local CNS radiotherapy in the Italian EAP real-world analysis (Passiglia et al., Lung Cancer 2024) without apparent increased toxicity. Adagrasib is also being studied prospectively in a study investigating concurrent SRS treatment in patients with brain metastases.