Hypofractionated Versus Conventional Chemoradiotherapy Followed by Consolidative Immunotherapy in Locally Advanced NSCLC

Summary

Consolidative immunotherapy following concurrent chemoradiotherapy, based on the PACIFIC trial, has become the standard treatment for locally advanced non-small cell lung cancer (LANSCLC). Radiotherapy strategies for maximizing efficacy and local control require further investigation. This phase III, randomized controlled clinical trial is to investigate the efficacy and safety of hypofractionated chemoradiotherapy followed by consolidative immunotherapy versus conventional fractionated chemoradiotherapy followed by consolidative immunotherapy in LANSCLC patients.

Timeline

Start

2025-07-01

Primary completion

2029-06-30

Completion

2029-06-30

Publications

• Background Zhou R, Liu F, Zhang H, Wang D, Zhang P, Zheng S, Liu Y, Chen L, Guo J, Zou Y, Rong YM, Liu H, Qiu B. Fraction Dose Escalation of Hypofractionated Radiotherapy with Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer: A Phase I Study. Clin Cancer Res. 2024 Jul 1;30(13):2719-2728. doi: 10.1158/1078-0432.CCR-23-3600.
• Background Filatenkov A, Baker J, Mueller AM, Kenkel J, Ahn GO, Dutt S, Zhang N, Kohrt H, Jensen K, Dejbakhsh-Jones S, Shizuru JA, Negrin RN, Engleman EG, Strober S. Ablative Tumor Radiation Can Change the Tumor Immune Cell Microenvironment to Induce Durable Complete Remissions. Clin Cancer Res. 2015 Aug 15;21(16):3727-39. doi: 10.1158/1078-0432.CCR-14-2824. Epub 2015 Apr 13.
• Background Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009 Jul 16;114(3):589-95. doi: 10.1182/blood-2009-02-206870. Epub 2009 Apr 6.
• Background Tang C, Liao Z, Gomez D, Levy L, Zhuang Y, Gebremichael RA, Hong DS, Komaki R, Welsh JW. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes. Int J Radiat Oncol Biol Phys. 2014 Aug 1;89(5):1084-1091. doi: 10.1016/j.ijrobp.2014.04.025. Epub 2014 Jul 8.
• Background Wild AT, Herman JM, Dholakia AS, Moningi S, Lu Y, Rosati LM, Hacker-Prietz A, Assadi RK, Saeed AM, Pawlik TM, Jaffee EM, Laheru DA, Tran PT, Weiss MJ, Wolfgang CL, Ford E, Grossman SA, Ye X, Ellsworth SG. Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2016 Mar 1;94(3):571-9. doi: 10.1016/j.ijrobp.2015.11.026. Epub 2015 Dec 1.
• Background Zhou R, Qiu B, Xiong M, Liu Y, Peng K, Luo Y, Wang D, Liu F, Chen N, Guo J, Zhang J, Huang X, Rong Y, Liu H. Hypofractionated Radiotherapy followed by Hypofractionated Boost with weekly concurrent chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Results of A Prospective Phase II Study (GASTO-1049). Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2):387-399. doi: 10.1016/j.ijrobp.2023.04.021. Epub 2023 Apr 25.
• Background Kong FM, Ten Haken RK, Schipper M, Frey KA, Hayman J, Gross M, Ramnath N, Hassan KA, Matuszak M, Ritter T, Bi N, Wang W, Orringer M, Cease KB, Lawrence TS, Kalemkerian GP. Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer: A Phase 2 Clinical Trial. JAMA Oncol. 2017 Oct 1;3(10):1358-1365. doi: 10.1001/jamaoncol.2017.0982.
• Background Durm GA, Jabbour SK, Althouse SK, Liu Z, Sadiq AA, Zon RT, Jalal SI, Kloecker GH, Williamson MJ, Reckamp KL, Langdon RM, Kio EA, Gentzler RD, Adesunloye BA, Harb WA, Walling RV, Titzer ML, Hanna NH. A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179. Cancer. 2020 Oct 1;126(19):4353-4361. doi: 10.1002/cncr.33083. Epub 2020 Jul 22.
• Background Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2.
• Background Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, Cho BC, Planchard D, Paz-Ares L, Faivre-Finn C, Vansteenkiste JF, Spigel DR, Wadsworth C, Taboada M, Dennis PA, Ozguroglu M, Antonia SJ. Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2020 Feb;15(2):288-293. doi: 10.1016/j.jtho.2019.10.002. Epub 2019 Oct 14.
• Background Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.

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