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PARP inhibitor

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

“Our findings show no evidence of excess hgAEs when intra- or extracranial SRT is delivered within one month of sacituzumab govitecan or PARP inhibitors. In contrast, prior publications suggest concomitant intra- or extra-cranial SRT during PARP inhibitors should not be offered[1] or major adaptations should be considered.[2] Yet important to note, the current 2.4% hgRTAE rate (n=3/125) was observed in a population in whom 74% paused their PARP inhibitor during SRT.”

“For poly(ADP-ribose) polymerase (PARP) inhibitors, four publications[3-6] (one prospective and three retrospective) included 125 patients treated with PARP inhibitors within one month of SRT (wmFUP: 20.9mo). Most patients (n=120; 96%) were treated for oligometastatic ovarian cancer and received SRT to various target sites, including brain, lung, liver, lymph nodes and other locations. Twenty-nine patients (23.2%) continued a PARP inhibitor throughout SRT, while 93 (74.4%) paused treatment for a few days before and after SRT. A hgRTAE rate of 2.4% (3/125) was observed.”

References (6)
  1. 1. Meattini I, Becherini C, Caini S, et al. International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations. Lancet Oncol. Feb 2024;25(2):e73–e83. doi:10.1016/s1470-2045(23)00534-x
  2. 2. van Aken ESM, Gandhi AK, O'Cathail SM, et al. ESMO-ESTRO consensus statements on the safety of combining radiotherapy with CDK4/6, HER2, PARP, or mTOR inhibitors. Radiother Oncol. Feb 2026;215:111330. doi:10.1016/j.radonc.2025.111330
  3. 3. 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
  4. 4. Durante S, Cuccia F, Rigo M, et al. Stereotactic radiotherapy for managing ovarian cancer oligoprogression under poly (ADP-ribose) polymerase inhibitors (PARPi). International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. May 31 2024; doi:10.1136/ijgc-2024-005361
  5. 5. Kroeze SGC, Schaule J, Fritz C, et al. Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy: efficacy and safety reporting from the 'TOaSTT' database. Radiat Oncol. Jan 6 2021;16(1):4. doi:10.1186/s13014-020-01730-0
  6. 6. Macchia G, Pezzulla D, Campitelli M, et al. Stereotactic Body Radiation Therapy for Oligoprogressive Ovarian Cancer Patients Treated During Poly(ADP-Ribose)-Polymerase Inhibitor Maintenance: Efficacy and Adverse Events From the Epimetheo Retrospective Study. Int J Radiat Oncol Biol Phys. 2025/02/01/ 2025;121(2):465–474. doi:10.1016/j.ijrobp.2024.09.010
Radiobiological rationale for RT–drug interaction
Potent broadly applicable radiosensitizer (PARP trapping → replication-associated DSBs; amplified in HR-deficient tumors). Sensitization is explicitly not tumor-specific and affects fast-proliferating normal tissue, providing a rationale for increased in-field mucosal, cutaneous, GI, and esophageal reactions, plus additive hematologic adverse events in marrow within the field (Jagsi et al., International Journal of Radiation Oncology, Biology, Physics, 2026).
The data above refer to patients treated with PARP inhibitor as the sole drug class, excluding any concurrent use of drugs from other groups.
Individual Drugs

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