Bevacizumab Combined With Fractionated Stereotactic Radiotherapy for 1 to 10 Brain Metastases From NSCLC

Summary

This Phase II randomized study is to determine the efficacy and safety of Bevacizumab combined with fractionated stereotactic radiation therapy(FSRT) in patients with 1 to 10 brain metastases in non-small cell lung cancer by assessing the treatment response, perilesional edema, neurological symptoms and quality of life.

Timeline

Start

2020-01-01

Primary completion

2023-03-31

Completion

2023-03-31

Outcome

Met primary endpoint

paper The Bev + FSRT group showed a significant improvement in IPFS compared to both the WBRT + FSRT group (9.6 months, P < 0.001) PMID 41235462 ↗

Publications

• Background Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
• Background Shaw MG, Ball DL. Treatment of brain metastases in lung cancer: strategies to avoid/reduce late complications of whole brain radiation therapy. Curr Treat Options Oncol. 2013 Dec;14(4):553-67. doi: 10.1007/s11864-013-0258-0.
• Background Yuan X, Liu WJ, Li B, Shen ZT, Shen JS, Zhu XX. A Bayesian network meta-analysis of whole brain radiotherapy and stereotactic radiotherapy for brain metastasis. Medicine (Baltimore). 2017 Aug;96(34):e7698. doi: 10.1097/MD.0000000000007698.
• Background Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, Beal K, Amini A, Patil T, Kavanagh BD, Camidge DR, Braunstein SE, Boreta LC, Balasubramanian SK, Ahluwalia MS, Rana NG, Attia A, Gettinger SN, Contessa JN, Yu JB, Chiang VL. Management of Brain Metastases in Tyrosine Kinase Inhibitor-Naive Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis. J Clin Oncol. 2017 Apr 1;35(10):1070-1077. doi: 10.1200/JCO.2016.69.7144. Epub 2017 Jan 23.
• Background Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016 Jul 26;316(4):401-409. doi: 10.1001/jama.2016.9839.
• Background Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, Shioura H, Inomata T, Kunieda E, Hayakawa K, Nakagawa K, Kobashi G, Shirato H. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1388-95. doi: 10.1016/j.ijrobp.2007.03.048.
• Background Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2.
• Background Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014 Apr;15(4):387-95. doi: 10.1016/S1470-2045(14)70061-0. Epub 2014 Mar 10.
• Background Serizawa T, Yamamoto M, Higuchi Y, Sato Y, Shuto T, Akabane A, Jokura H, Yomo S, Nagano O, Kawagishi J, Yamanaka K. Local tumor progression treated with Gamma Knife radiosurgery: differences between patients with 2-4 versus 5-10 brain metastases based on an update of a multi-institutional prospective observational study (JLGK0901). J Neurosurg. 2019 Apr 26;132(5):1480-1489. doi: 10.3171/2019.1.JNS183085. Print 2020 May 1.
• Background Rades D, Janssen S, Dziggel L, Blanck O, Bajrovic A, Veninga T, Schild SE. A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases. BMC Cancer. 2017 Jan 6;17(1):30. doi: 10.1186/s12885-016-2989-3.
• Background Manning MA, Cardinale RM, Benedict SH, Kavanagh BD, Zwicker RD, Amir C, Broaddus WC. Hypofractionated stereotactic radiotherapy as an alternative to radiosurgery for the treatment of patients with brain metastases. Int J Radiat Oncol Biol Phys. 2000 Jun 1;47(3):603-8. doi: 10.1016/s0360-3016(00)00475-2.
• Background Baliga S, Garg MK, Fox J, Kalnicki S, Lasala PA, Welch MR, Tome WA, Ohri N. Fractionated stereotactic radiation therapy for brain metastases: a systematic review with tumour control probability modelling. Br J Radiol. 2017 Feb;90(1070):20160666. doi: 10.1259/bjr.20160666. Epub 2016 Dec 12.
• Background Mekhail T, Sombeck M, Sollaccio R. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. Curr Oncol Rep. 2011 Aug;13(4):255-8. doi: 10.1007/s11912-011-0180-1. No abstract available.
• Background Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006 Jun 7;295(21):2483-91. doi: 10.1001/jama.295.21.2483.
• Background Barrett OC, McDonald AM, Thompson JW, Bredel M, McGwin G, Riley KO, Fiveash JB. Distant brain recurrence in patients with five or more newly diagnosed brain metastases treated with focal stereotactic radiotherapy alone. J Radiosurg SBRT. 2017;4(4):255-263.
• Background Socinski MA, Langer CJ, Huang JE, Kolb MM, Compton P, Wang L, Akerley W. Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. J Clin Oncol. 2009 Nov 1;27(31):5255-61. doi: 10.1200/JCO.2009.22.0616. Epub 2009 Sep 8.
• Background Zustovich F, Ferro A, Lombardi G, Zagonel V, Fiduccia P, Farina P. Bevacizumab as front-line treatment of brain metastases from solid tumors: a case series. Anticancer Res. 2013 Sep;33(9):4061-5.
• Background Jiang T, Zhang Y, Li X, Zhao C, Chen X, Su C, Ren S, Yang N, Zhou C. EGFR-TKIs plus bevacizumab demonstrated survival benefit than EGFR-TKIs alone in patients with EGFR-mutant NSCLC and multiple brain metastases. Eur J Cancer. 2019 Nov;121:98-108. doi: 10.1016/j.ejca.2019.08.021. Epub 2019 Sep 27.
• Background Boothe D, Young R, Yamada Y, Prager A, Chan T, Beal K. Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro Oncol. 2013 Sep;15(9):1257-63. doi: 10.1093/neuonc/not085. Epub 2013 Jun 27.
• Background Yomo S, Hayashi M. Salvage stereotactic radiosurgery with adjuvant use of bevacizumab for heavily treated recurrent brain metastases: a preliminary report. J Neurooncol. 2016 Mar;127(1):119-26. doi: 10.1007/s11060-015-2019-3. Epub 2015 Nov 30.
• Background Xiangying M, Rugang Z, Lijuan D, Yaowei Z, Bing S, Junliang W, Dan L, Shikai W. Low-dose bevacizumab as an effective pre-treatment for peri-tumoral brain edema prior to CyberKnife radiosurgery: A case report. Cancer Biol Ther. 2018 Jun 3;19(6):461-464. doi: 10.1080/15384047.2018.1433499. Epub 2018 Mar 21.
• Background Levy C, Allouache D, Lacroix J, Dugue AE, Supiot S, Campone M, Mahe M, Kichou S, Leheurteur M, Hanzen C, Dieras V, Kirova Y, Campana F, Le Rhun E, Gras L, Bachelot T, Sunyach MP, Hrab I, Geffrelot J, Gunzer K, Constans JM, Grellard JM, Clarisse B, Paoletti X. REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours. Ann Oncol. 2015 Nov;26(11):2359. doi: 10.1093/annonc/mdv386. No abstract available.
• Background Clarke J, Neil E, Terziev R, Gutin P, Barani I, Kaley T, Lassman AB, Chan TA, Yamada J, DeAngelis L, Ballangrud A, Young R, Panageas KS, Beal K, Omuro A. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. Int J Radiat Oncol Biol Phys. 2017 Nov 15;99(4):797-804. doi: 10.1016/j.ijrobp.2017.06.2466. Epub 2017 Jun 30.
• Background Eisele SC, Wen PY, Lee EQ. Assessment of Brain Tumor Response: RANO and Its Offspring. Curr Treat Options Oncol. 2016 Jul;17(7):35. doi: 10.1007/s11864-016-0413-5.
• Zhou R, Zheng S, Wang D, Dong F, Zhang H, Zhang T, Luo Q, Liu B, Liu H, Zhang J, Liu F, Wang B, Chen L, Mou Y, Peng K, Qiu B, Liu H. Efficacy and safety of combining bevacizumab and fractionated stereotactic radiotherapy for extensive brain metastases in patients with non-small cell lung cancer: a prospective phase II study (GASTO-1053). Cancer Commun (Lond). 2025 Dec;45(12):1739-1754. doi: 10.1002/cac2.70078. Epub 2025 Nov 14.

Drugs

Indications