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Group

Multi-target TKI

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

“The combination of multi-target TKI within one month of SRT generally did not lead to excess hgAE rates; in a subset, however, TKIs were withheld during or started after SRT. In contrast, for those patients treated with liver SRT, a rate of 40.5% hgOAEs was observed. As the drug in monotherapy can lead to high AE rates,[1,2] the added risk from SRT is uncertain, warranting caution for this combination, which is in line with previous reports.[3-5]”

“For multi-target tyrosine kinase inhibitors (TKI), nineteen publications[6-24] comprising 770 patients were identified (weighted median follow-up [wmFUP]: 18.6mo). The following rates of hgAEs were observed: 16.5% for OAEs (91/551); 1.8% for RTAEs (4/219). No increased AE rate was noted for brain, lung or spinal SRT (Fig 4a).

Three studies[7,14,17] (two prospective and one retrospective) included 138 patients treated with liver SRT within one month of lenvatinib or sorafenib (wmFUP: 21.3mo). Two studies included 120 patients who started lenvatinib/sorafenib within one week after completion of SRT whereas one study included 18 patients who started sorafenib one week before SRT. Overall, 40.5% of patients (56/138) experienced high grade OAEs (hgOAEs). In the study with sorafenib administered during SRT, 10 of 18 patients developed hgOAEs, including one in-field event; number of in-field AEs were not reported for the other studies.”

“Two studies[15,24] (one prospective and one retrospective) included 31 patients treated with brain SRT within one month of a multi-target TKI (wmFUP: 18mo). The TKI was paused during SRT in a subset (number not reported). One patient (3.2%) experienced hgAEs, related to SRT.

Two studies[13,24] (one prospective and one retrospective) included 11 patients treated with lung SRT within one month of multi-target TKI (wmFUP: 16mo). Two patients (18%) experienced high grade RTAEs (hgRTAEs).

One retrospective study[2] included 70 patients treated with spinal SRT with concurrent sunitinib/axitinib/pazopanib/sorafenib (wmFUP:13.7mo). SRT doses ranged from 10-18Gy in a single fraction. All patients received multi-target TKI on the day of SRT and no hgRTAEs were reported.”

References (24)
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  5. 5. van Aken ESM, Devnani B, Prelaj A, et al. ESMO-ESTRO consensus statements on the safety of combining radiotherapy with immune checkpoint inhibitors, VEGF(R) inhibitors, or multitargeted tyrosine kinase inhibitors. Ann Oncol. Jan 2026;37(1):17–32. doi:10.1016/j.annonc.2025.09.008
  6. 6. Cheung P, Patel S, North SA, et al. Stereotactic Radiotherapy for Oligoprogression in Metastatic Renal Cell Cancer Patients Receiving Tyrosine Kinase Inhibitor Therapy: A Phase 2 Prospective Multicenter Study. Eur Urol. Dec 2021;80(6):693–700. doi:10.1016/j.eururo.2021.07.026
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  13. 13. Goldsmith RM, Xing JL, Heal CW, De La Maza MC, Stea B. Stereotactic Body Radiation Therapy and Concurrent Targeted Therapy for Lung Metastases in Pediatric Sarcoma. Adv Radiat Oncol. Jul 2024;9(7):101517. doi:10.1016/j.adro.2024.101517
  14. 14. Goody RB, Brade AM, Wang L, et al. Phase I trial of radiation therapy and sorafenib in unresectable liver metastases. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. May 2017;123(2):234–239. doi:10.1016/j.radonc.2017.01.018
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  17. 17. Ji X, Xu Z, Sun J, Li W, Duan X, Wang Q. Lenvatinib with or without stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective study. Radiat Oncol. Jun 12 2023;18(1):101. doi:10.1186/s13014-023-02270-z
  18. 18. Kao J, Chen CT, Tong CC, et al. Concurrent sunitinib and stereotactic body radiotherapy for patients with oligometastases: final report of a prospective clinical trial. Target Oncol. Jun 2014;9(2):145–53. doi:10.1007/s11523-013-0280-y
  19. 19. Keane FK, Yeap BY, Khandekar MJ, et al. Phase 2 Trial of Consolidative Stereotactic Body Radiation Therapy in Patients With Metastatic Oncogene-driven Non-small Cell Lung Carcinoma Treated With Tyrosine Kinase Inhibitors. Int J Radiat Oncol Biol Phys. 2025/03/15/ 2025;121(4):975–979. doi:10.1016/j.ijrobp.2024.10.022
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  23. 23. Yang E, Yu JI, Park HC, et al. Safety and Efficacy of Combining Metastasis-Directed Stereotactic Ablative Radiation Therapy with Tyrosine Kinase Inhibitors Versus Immune Checkpoint Inhibitors in Metastatic Hepatocellular Carcinoma. Cancer Res Treat. 2026/02/03/ 2026; doi:10.4143/crt.2025.966
  24. 24. 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
Radiobiological rationale for RT–drug interaction
Radiosensitizing via VEGFR/PDGFR and RAS–MEK–ERK/PI3K–AKT blockade, vascular normalization, and S-phase depletion (Viktorsson et al., Strahlentherapie und Onkologie, 2023; Affolter et al., Head & Neck, 2017; Shen et al., European Journal of Medical Research, 2026). Because the antiangiogenic and DNA-repair effects are not tumor-restricted, a theoretical increase in normal-tissue adverse events is plausible—chiefly vascular/ischemic injury and impaired healing in irradiated tissue, with the bowel and other visceral organs the principal concern.
The data above refer to patients treated with Multi-target TKI 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

Select a drug to view its individual evidence base (drug + SBRT, no other concurrent systemic drugs). Drugs without available data are shown greyed out.

Axitinib Cabozantinib Crizotinib Lapatinib Lenvatinib Pazopanib Sorafenib Sunitinib Avapritinib
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 Entrectinib
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 Nilotinib
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 Nintedanib
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 Regorafenib
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 Repotrectinib
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 Ripretinib
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 Vandetanib
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