PMID- 36260832 OWN - NLM STAT- MEDLINE DCOM- 20230217 LR - 20240221 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 41 IP - 6 DP - 2023 Feb 20 TI - NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma. PG - 1285-1295 LID - 10.1200/JCO.22.00164 [doi] AB - PURPOSE: To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities. METHODS: NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression >/= 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression. RESULTS: From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; P = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; P = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, P = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM. CONCLUSION: To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS. FAU - Tsien, Christina I AU - Tsien CI AUID- ORCID: 0000-0002-5458-5732 AD - Johns Hopkins School of Medicine, Baltimore, MD. FAU - Pugh, Stephanie L AU - Pugh SL AD - NRG Oncology Statistics and Data Management Center, Philadelphia, PA. FAU - Dicker, Adam P AU - Dicker AP AUID- ORCID: 0000-0003-0733-3337 AD - Thomas Jefferson University, Philadelphia, PA. FAU - Raizer, Jeffrey J AU - Raizer JJ AD - Northwestern University, Chicago, IL. FAU - Matuszak, Martha M AU - Matuszak MM AD - University of Michigan, Ann Arbor, MI. FAU - Lallana, Enrico C AU - Lallana EC AD - Kaiser Permanente Sacramento Medical Center, Sacramento, CA. FAU - Huang, Jiayi AU - Huang J AUID- ORCID: 0000-0002-5153-506X AD - Washington University School of Medicine in St Louis-Siteman Cancer Center, St. Louis, MO. FAU - Algan, Ozer AU - Algan O AD - University of Oklahoma Health Sciences Center, Oklahoma City, OK. FAU - Deb, Nimisha AU - Deb N AD - St Luke's University Hospital & Health Network accruals Thomas Jefferson University Hospital, Bethlehem, PA. FAU - Portelance, Lorraine AU - Portelance L AD - University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center, Miami, FL. FAU - Villano, John L AU - Villano JL AUID- ORCID: 0000-0001-5583-0093 AD - University of Kentucky/Markey Cancer Center, Lexington, KY. FAU - Hamm, John T AU - Hamm JT AD - Norton Hospital Pavilion and Medical Campus, Louisville, KY. FAU - Oh, Kevin S AU - Oh KS AD - Dana-Farber/Harvard Cancer Center, Boston, MA. FAU - Ali, Arif N AU - Ali AN AUID- ORCID: 0000-0003-3860-1242 AD - The Hope Center accruals Emory University/Winship Cancer Institute, Dalton, GA. FAU - Kim, Michelle M AU - Kim MM AD - University of Michigan Comprehensive Cancer Center, Ann Arbor, MI. FAU - Lindhorst, Scott M AU - Lindhorst SM AUID- ORCID: 0000-0002-1585-4450 AD - Medical University of South Carolina Minority Underserved NCORP, Charleston, SC. FAU - Mehta, Minesh P AU - Mehta MP AUID- ORCID: 0000-0002-4812-5713 AD - Miami Cancer Institute, Miami, FL. LA - eng SI - ClinicalTrials.gov/NCT01730950 GR - U10 CA180822/CA/NCI NIH HHS/United States GR - U10 CA180868/CA/NCI NIH HHS/United States GR - UG1 CA233160/CA/NCI NIH HHS/United States GR - UG1 CA233339/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20221019 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 2S9ZZM9Q9V (Bevacizumab) SB - IM CIN - 1183 MH - Humans MH - Bevacizumab MH - *Glioblastoma/drug therapy/radiotherapy MH - *Re-Irradiation/adverse effects MH - Prospective Studies MH - *Brain Neoplasms/drug therapy/radiotherapy MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects PMC - PMC9940937 COIS- Christina I. Tsien Speakers' Bureau: Varian Medical Systems Travel, Accommodations, Expenses: Zeiss Stephanie L. Pugh Research Funding: Pfizer (Inst), Millennium (Inst) Adam P. Dicker Stock and Other Ownership Interests: OncoHost Consulting or Advisory Role: EMD Serono, Janssen, Roche, Cybrexa Therapeutics, OncoHost, Third Bridge, Accordant, Alcimed, Orano Med, IBA, Genentech, Deallus, CVS, Hengrui Pharmaceutical, Voluntis Patents, Royalties, Other Intellectual Property: We recently filed a patent "Doped BEO Compounds for Optically Stimulated Luminescence (OSL) and Thermoluminescence (TL) Radiation Dosimetry" Expert Testimony: Wilson Sonsini Travel, Accommodations, Expenses: OncoHost Other Relationship: European Commission Uncompensated Relationships: Google, Dreamit Ventures Jeffrey J. Raizer Employment: Astellas Pharma Stock and Other Ownership Interests: Agenus, Exicure, Cancer Action Now Martha M. Matuszak Consulting or Advisory Role: Varian Medical Systems Research Funding: Varian Medical Systems Other Relationship: Blue Cross Blue Shield of Michigan Enrico C. Lallana Employment: The Permanente Medical Group Stock and Other Ownership Interests: The Permanente Medical Group Open Payments Link: https://openpaymentsdata.cms.gov/physician/483578 Jiayi Huang Research Funding: Cantex Pharmaceuticals, Pfizer/EMD Serono Lorraine Portelance Research Funding: ViewRay (Inst) Travel, Accommodations, Expenses: RefleXion Medical John T. Hamm Consulting or Advisory Role: Meda Pharmaceuticals Research Funding: AbbVie (Inst), Amgen (Inst), ARMO BioSciences (Inst), Astellas Pharma (Inst), AstraZeneca (Inst), Boehringer Ingelheim (Inst), Boston Biomedical (Inst), BrightPath Biotherapeutics (Inst), Bristol Myers Squibb (Inst), Cancer Research and Biostatistics (Inst), Celgene (Inst), Clovis Oncology (Inst), Daiichi Sankyo (Inst), Dana-Farber Cancer Institute (Inst), Deciphera (Inst), Lilly (Inst), EMD Serono (Inst), EpicentRx (Inst), Exact Sciences (Inst), Roche (Inst), Five Prime Therapeutics (Inst), G1 Therapeutics (Inst), GBG Forschungs (Inst), Genentech (Inst), Gilead Sciences (Inst), GlaxoSmithKline (Inst), Gynecologic Oncology Group (Inst), Halozyme (Inst), Immunicum (Inst), Incyte (Inst), Infinity Pharmaceuticals (Inst), Janssen (Inst), Jiangsu Hengrui Medicine (Inst), Johnson & Johnson (Inst), MedImmune (Inst), Merck (Inst), Moffitt (Inst), National Surgical Adjuvant Breast and Bowel Project (Inst), Nektar (Inst), Novartis (Inst), OncoMed (Inst), Pfizer (Inst), PharmaMar (Inst), Plexxikon (Inst), Pronova (Inst), Sarah Cannon Research Institute (Inst), Seattle Genetics (Inst), SWOG (Inst), Spectrum Pharmaceuticals (Inst) Arif N. Ali Leadership: Northwest Georgia Radiation Oncology, LLC Stock and Other Ownership Interests: Northwest Georgia Radiation Oncology Michelle M. Kim Consulting or Advisory Role: Blue Earth Diagnostics (Inst) Research Funding: EpicentRx (Inst), Blue Earth Diagnostics (Inst) Travel, Accommodations, Expenses: Capital Health Minesh P. Mehta Leadership: Oncoceutics Stock and Other Ownership Interests: Chimerix Consulting or Advisory Role: Karyopharm Therapeutics, Mevion Medical Systems, ZappRx, Sapience Therapeutics, Xoft Patents, Royalties, Other Intellectual Property: WARF patent 14/934,27, Topical Vasoconstrictor Preparations and Methods for Protecting Cells During Cancer Chemotherapy and Radiotherapy Uncompensated Relationships: Xcision Medical Systems, ViewRay No other potential conflicts of interest were reported. EDAT- 2022/10/20 06:00 MHDA- 2023/02/18 06:00 PMCR- 2024/02/20 CRDT- 2022/10/19 16:03 PHST- 2022/10/20 06:00 [pubmed] PHST- 2023/02/18 06:00 [medline] PHST- 2022/10/19 16:03 [entrez] PHST- 2024/02/20 00:00 [pmc-release] AID - JCO.22.00164 [pii] AID - 10.1200/JCO.22.00164 [doi] PST - ppublish SO - J Clin Oncol. 2023 Feb 20;41(6):1285-1295. doi: 10.1200/JCO.22.00164. Epub 2022 Oct 19.