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Effect of previous radiotherapy on the efficacy and pulmonary toxicity of PD-1 inhibitor in second-line or above treatment in patients with stage Ⅳ non-small cell lung cancer
Chen Huijing1, He Chunyu1, Ge Hong1, Nie Xin1, Liu Ru1, Wu Xiaoyuan1, Jiao Shuyue2, Ma Cong1
1Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008,China; 2Department of Respiration, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital,Zhengzhou 450008,China
AbstractObjective To investigate whether radiotherapy should be delivered before the application of immune checkpoint inhibitor PD-1 in patients with advanced non-small cell lung cancer (NSCLC) and evaluate the effect of previous radiotherapy on the efficacy and pulmonary toxicity of PD-1 inhibitor. Methods Clinical data of patients with stage Ⅳ NSCLC who received immunotherapy in Henan Cancer Hospital from March 2015 to September 2019 were retrospectively analyzed. The baseline data of patients, the status of radiotherapy and immunotherapy and the pulmonary toxicity were collected. According to whether radiotherapy was given before PD-1 inhibitor application, all patients were divided into the previous radiotherapy and non-radiotherapy groups. Survival analysis was performed by Kaplan-Meier method. Results A total of 90 patients were enrolled including 39 cases in the previous radiotherapy group and 51 cases in the non-radiotherapy group. The median follow-up time was 22.9 months. The median progression-free survival (mPFS) in the previous radiotherapy group was 7.5 months (95%CI 5.4-9.5 months), significantly longer compared with 4.1 months (95%CI 3.1-5.1 months) in the non-radiotherapy group (P=0.003). The median overall survival (mOS) significantly differed between two groups[15.2 months (95%CI 12.3-18.1 months) vs. 9.3 months (95%CI 6.1-12.5 months)](P=0.040). The incidence of pulmonary toxicity showed no significant difference between two groups (P=0.154). Conclusions Patients with stage Ⅳ NSCLC patients in the previous radiotherapy group obtain significantly better mPFS and mOS and similar pulmonary toxicity compared with their counterparts in the non-radiotherapy group. Nevertheless, the findings remain to be validated by subsequent investigations with larger sample size.
Fund:Nationl Natural Science Foundation of China (81773230);Project of Tackling Key Problems in Technology of Henan Province (202102310114)
Corresponding Authors:
He Chunyu, Email:15003883759@163.com;Ge Hong,Email:gehong666@126.com
Cite this article:
Chen Huijing,He Chunyu,Ge Hong et al. Effect of previous radiotherapy on the efficacy and pulmonary toxicity of PD-1 inhibitor in second-line or above treatment in patients with stage Ⅳ non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2021, 30(4): 348-352.
Chen Huijing,He Chunyu,Ge Hong et al. Effect of previous radiotherapy on the efficacy and pulmonary toxicity of PD-1 inhibitor in second-line or above treatment in patients with stage Ⅳ non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2021, 30(4): 348-352.
[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1):7-30. DOI:10.3322/caac.21590. [2] Zheng R, Zeng H, Zhang S, et al. Estimates of cancer incidence and mortality in China, 2013[J]. Chin J Cancer, 2017, 36(1):66. DOI:10.1186/s40880-017-0234-3. [3] Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018:GLOBOCAN sources and methods[J]. Int J Cancer, 2019, 144(8):1941-1953. DOI:10.1002/ijc.31937. [4] Shaverdian N, Lisberg AE, Bornazyan K, et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer:a secondary analysis of the KEYNOTE-001 phase 1 trial[J]. Lancet Oncol, 2017, 18(7):895-903. DOI:10.1016/S1470-2045(17)30380-7. [5] Seymour L, Bogaerts J, Perrone A, et al. iRECIST:guidelines for response criteria for use in trials testing immunotherapeutics[J]. Lancet Oncol, 2017, 18(3):e143-e152. DOI:10.1016/s1470-2045(17)30074-8. [6] Gainor JF. Moving programmed death-1 inhibitors to the front lines in non-small-cell lung cancer[J]. J Clin Oncol, 2016, 34(25):2953-2955. DOI:10.1200/JCO.2016.68.1205. [7] Melosky B, Chu Q, Juergens R, et al. Pointed progress in second-line advanced non–small-cell lung cancer:the rapidly evolving field of checkpoint inhibition[J]. J Clin Oncol, 2016, 34(14):1676-1688. DOI:10.1200/jco.2015.63.8049. [8] Gray JE, Villegas A, Daniel D, et al. Three-year overall survival with durvalumab after chemoradiotherapy in stage Ⅲ NSCLC-update from PACIFIC[J]. J Thorac Oncol, 2020, 15(2):288-293. DOI:10.1016/j.jtho.2019.10.002. [9] Formenti SC, Demaria S. Radiation therapy to convert the tumor into an in situ vaccine[J]. Int J Radiat Oncol Bio Phys, 2012, 84(4):879-880. DOI:10.1016/j.ijrobp.2012.06.020. [10] Demaria S, Golden EB, Formenti SC. Role of local radiation therapy in cancer immunotherapy[J]. JAMA Oncol, 2015, 1(9):1325-1332. DOI:10.1001/jamaoncol.2015.2756. [11] Sharabi AB, Lim M, DeWeese TL, et al. Radiation and checkpoint blockade immunotherapy:radiosensitisation and potential mechanisms of synergy[J]. Lancet Oncol, 2015, 16(13):e498-e509. DOI:10.1016/s1470-2045(15)00007-8. [12] Escorcia FE, Postow MA, Barker CA. Radiotherapy and immune checkpoint blockade for melanoma:a promising combinatorial strategy in need of further investigation[J]. Cancer J, 2017, 23(1):32-39. DOI:10.1097/PPO.0000000000000236. [13] Rudd CE, Taylor A, Schneider H. CD28 and CTLA-4 coreceptor expression and signal transduction[J]. Immunological Reviews, 2009, 229(1):12-26. DOI:10.1111/j.1600-065X.2009.00770.x. [14] Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways[J]. Immunol Rev, 2008, 224:166-182. DOI:10.1111/j.1600-065X.2008.00662.x. [15] Collison LW, Vignali DA. in vitro Treg suppression assays[J]. Meth Mol Biol, 2011, 707:21-37. DOI:10.1007/978-1-61737-979-6_2. [16] 袁梦,门玉,惠周光,等. NSCLC放疗联合免疫治疗研究进展[J]. 中华放射肿瘤学杂志, 2018, 27(5):533-537. DOI:10.3760/cma.j.issn.1004-4221.2018.05.020. Yuan M, Men Y, Hui ZG, et al. Research progress in radiotherapy combined with immunotherapy for non-small cell lung cancer[J]. Chin J Radiat Oncol, 2018, 27(5):533-537. DOI:10.3760/cma.j.issn.1004-4221.2018.05.020. [17] Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer[J]. N Engl J Med, 2015, 373(2):123-135. DOI:10.1056/NEJMoa1504627. [18] Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma[J]. N Engl J Med, 2015, 373(19):1803-1813. DOI:10.1056/NEJMoa1510665. [19] Rizvi NA, Mazières J, Planchard D, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063):a phase 2, single-arm trial[J]. Lancet Oncol, 2015, 16(3):257-265. DOI:10.1016/s1470-2045(15)70054-9. [20] Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR):a multicentre, open-label, phase 2 randomised controlled trial[J]. Lancet, 2016, 387(10030):1837-1846. DOI:10.1016/s0140-6736(16)00587-0. [21] Arnaud-Coffin P, Maillet D, Gan HK, et al. A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors[J]. Int J Cancer, 2019, 145(3):639-648. DOI:10.1002/ijc.32132.