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Group

MEK inhibitor

Study design
RT–Drug Timing Window
Data: details & interpretation
Excerpts from the LINACS publication (Sundahl et al., Radiother Oncol 2026):

“...Similarly, BRAF/MEK inhibitors with (mainly brain) SRT within the same month showed a high rate (20.5%) of high-grade RTAEs (albeit in a limited sample size). This is consistent with reports of increased AEs combining conventionally fractionated radiotherapy with BRAF/MEK inhibitors.[1]”

“Two publications[2,3] (one prospective and one retrospective) included 44 patients treated with BRAF/MEK inhibitors within one month of SRT (wmFUP: 17.8). In at least a subset of patients, treatment was paused during SRT, although the exact number was not reported. The rate of hgRTAEs was 20.5% (9/44).

The majority of the patients (n=38; 86.4%) received brain SRT. Within this subgroup, treatment was paused in 12 patients, initiated sequentially after SRT in 10 patients and continued concurrently with SRT in 16 patients. Eight patients (21%) who received brain SRT experienced hgRTAEs. Whether systemic therapy was paused, sequential, or concurrent in the patients who developed AEs was not reported. The remaining five patients received SRT to extracranial sites (abdomen, pelvis and lung). One of these patients experienced a high-grade RTAE.”

References (3)
  1. 1. Anker CJ, Grossmann KF, Atkins MB, Suneja G, Tarhini AA, Kirkwood JM. Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG). Int J Radiat Oncol Biol Phys. Jun 1 2016;95(2):632–46. doi:10.1016/j.ijrobp.2016.01.038
  2. 2. Looman EL, Kroeze SGC, Schaule J, et al. Adverse Events After Metastases-Directed Stereotactic Radiotherapy and Biological Cancer Therapy. JAMA Netw Open. 2026/01/02/ 2026;9(1):e2553809. doi:10.1001/jamanetworkopen.2025.53809
  3. 3. Patel BG, Ahmed KA, Johnstone PA, Yu HH, Etame AB. Initial experience with combined BRAF and MEK inhibition with stereotactic radiosurgery for BRAF mutant melanoma brain metastases. Melanoma Res. Aug 2016;26(4):382–6. doi:10.1097/cmr.0000000000000250
Radiobiological rationale for RT–drug interaction
Radiosensitizing across tumor types (mitotic catastrophe, ↓HR/checkpoint, cGAS-STING). As a non-selective ERK-pathway sensitizer that also affects normal proliferating epithelium, it provides a rationale for additive in-field mucocutaneous adverse events(Anker et al., ECOG consensus review, 2016).
The data above refer to patients treated with MEK inhibitor as the sole drug class, excluding any concurrent use of drugs from other groups. Combination therapy data are available in the section below.
Individual Drugs

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Binimetinib
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 Cobimetinib
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 Trametinib
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