广泛期小细胞肺癌诱导治疗后胸部放疗序贯PD-1/PD-L1抑制剂的安全性研究

doi:10.3760/cma.j.cn113030-20211014-00407

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Abstract Objective To evaluate the safety and tolerance of sequential thoracic radiotherapy combined with PD-1/PD-L1 inhibitors in patients with extensive-stage small cell lung cancer (ES-SCLC) after induction systemic therapy. Methods ES-SCLC patients from a phase I trial and a real-world study were enrolled for those who received thoracic radiotherapy after induction systemic treatment (chemotherapy/chemotherapy combined with PD-1/PD-L1 inhibitors) and consolidated with PD-1/PD-L1 inhibitors. These two studies were both approved by the Ethics Committee of Chinese Academy of Medical Sciences Cancer Hospital (Clinical Trials.gov number, NCT03971214, NCT04947774). Results Between January 2019 and March 2021, a total of 11 patients with ES-SCLC were analyzed, aged 52-73 years, with a median age of 62 years. Among them, five patients (45.5%) received induction chemotherapy and six patients (54.5%) received chemotherapy combined with PD-1/PD-L1 inhibitor, and then all received intensity-modulated thoracic radiotherapy after evaluation of systemic treatment efficacy. Two patients developed treatment-related grade G3-5 toxicity (18.2%, 1 treatment-related pneumonitis and 1 radiation esophagitis). G1-G2hematologic toxicity, pneumonia, and anorexia were common mild toxicities. Only one patient (9.1%) terminated immunotherapy due to immune-related pneumonitis. During a median follow-up time of 12.5 months (range:3.5-16.4 months),the median disease progression-free survival and overall survival was 7.4 months (95%CI:6.9-8.0 months) and 14.6 months (95%CI:9.0-20.2 months), respectively. Conclusions Sequential thoracic radiotherapy followed by PD-1/PD-L1 inhibitor is safe and feasible in patients with ES-SCLC after induction therapy. Given that both thoracic radiotherapy and immunotherapy benefits the ES-SCLC in survival, this comprehensive treatment modality warrants further investigation.

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	Articles by authors
	Liu Wenyang
	Han Ziming
	Wang Jianyang
	Zhang Tao
	Chen Dongfu
	Feng Qinfu
	Xiao Zefen
	Lyu Jima
	Wang Xin
	Deng Lei
	Wang Wenqing
	Zhai Yirui
	Wang Zhijie
	Wang Jie
	Bi Nan
	Zhou Zongmei

Key words： Carcinoma, small cell lung, extensive stage/chemotherapy Carcinoma, small cell lung, extensive stage/radiotherapy Carcinoma, small cell lung, extensive stage/immunotherapy

Received: 14 October 2021

Fund:Beijing Hope Run Special Fund of Cancer Foundation of China (LC2018A04) DOI:10.3760/cma.j.cn113030-20211014-00407

Corresponding Authors: Bi Nan, Email:binan_email@163.com;Zhou Zongmei, Email:zhouzongmei2013@163.com

Cite this article:

Liu Wenyang,Han Ziming,Wang Jianyang et al. Safety of thoracic radiotherapy followed by PD-1/PD-L1 inhibitor after induction therapy for extensive-stage small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2022, 31(3): 236-241.

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http://journal12.magtechjournal.com/Jweb_fszlx/EN/10.3760/cma.j.cn113030-20211014-00407 OR http://journal12.magtechjournal.com/Jweb_fszlx/EN/Y2022/V31/I3/236

[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71:209-249. DOI:10.3322/caac.21660.
[2] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132. DOI:10.3322/caac.21338.
[3] Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1):7-33. DOI:10.3322/caac.21654.
[4] Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer[J]. N Engl J Med, 2018, 379(23):2220-2229. DOI:10.1056/NEJMoa1809064.
[5] Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN):a randomised, controlled, open-label, phase 3 trial[J]. Lancet, 2019, 394(10212):1929-1939. DOI:10.1016/S0140-6736(19)32222-6.
[6] Rudin CM, Awad MM, Navarro A, et al. Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer:randomized, double-blind, phase Ⅲ KEYNOTE-604 study[J]. J Clin Oncol, 2020, 38(21):2369-2379. DOI:10.1200/JCO.20.00793.
[7] Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer:A randomized study[J]. J Clin Oncol, 1999, 17(7):2092-2099. DOI:10.1200/JCO.1999.17.7.2092.
[8] Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer:a phase 3 randomised controlled trial[J]. Lancet, 2015, 385(9962):36-42. DOI:10.1016/S0140-6736(14)61085-0.
[9] Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer[J]. N Engl J Med, 2017, 377(20):1919-1929. DOI:10.1056/NEJMoa1709937.
[10] Welsh JW, Heymach JV, Chen D, et al. Phase I trial of pembrolizumab and radiation therapy after induction chemotherapy for extensive-stage small cell lung cancer[J]. J Thorac Oncol, 2020, 15(2):266-273. DOI:10.1016/j.jtho.2019.10.001.
[11] Wang D, Bi N, Zhang T, et al. Comparison of efficacy and safety between simultaneous integrated boost intensity-modulated radiotherapy and conventional intensity-modulated radiotherapy in locally advanced non-small-cell lung cancer:a retrospective study[J]. Radiat Oncol, 2019, 14(1):106. DOI:10.1186/s13014-019-1259-3.
[12] Jabbour SK, Lee KH, Frost N, et al. Pembrolizumab plus concurrent chemoradiation therapy in patients with unresectable, locally advanced, stage Ⅲ non-small cell lung cancer:the phase 2 keynote-799 nonrandomized trial[J]. JAMA Oncol, 2021, DOI:10.1001/jamaoncol.2021.2301.
[13] Peters S, Felip E, Dafni U, et al. Progression-free and overall survival for concurrent nivolumab with standard concurrent chemoradiotherapy in locally advanced stage ⅢA-B NSCLC:results from the european thoracic oncology platform NICOLAS phase Ⅱ trial (european thoracic oncology platform 6-14)[J]. J Thorac Oncol, 2021, 16(2):278-288. DOI:10.1016/j.jtho.2020.10.129.
[14] Durm GA, Jabbour SK, Althouse SK, et al. 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[J]. Cancer, 2020, 126(19):4353-4361. DOI:10.1002/cncr.33083.
[15] Lin SH, Lin Y, Yao L, et al. Phase Ⅱ trial of concurrent atezolizumab with chemoradiation for unresectable NSCLC[J]. J Thorac Oncol, 2020, 15(2):248-257. DOI:10.1016/j.jtho.2019.10.024.
[16] Zhou X, Yao Z, Bai H, et al. Treatment-related adverse events of PD-1 and PD-L1 inhibitor-based combination therapies in clinical trials:a systematic review and meta-analysis[J]. Lancet Oncol, 2021, 22(9):1265-1274. DOI:10.1016/S1470-2045(21)00333-8.
[17] von Reibnitz D, Chaft JE, Wu AJ, et al. Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition[J]. Adv Radiat Oncol, 2018, 3(3):391-398. DOI:10.1016/j.adro.2018.05.001.
[18] Simone CB 2nd, Bogart JA, Cabrera AR, et al. Radiation therapy for small cell lung cancer:an ASTRO clinical practice guideline[J]. Pract Radiat Oncol, 2020, 10(3):158-173. DOI:10.1016/j.prro.2020.02.009.
[19] Chun SG, Simone CB 2nd, Amini A, et al. American radium society appropriate use criteria:radiation therapy for limited-stage SCLC 2020[J]. J Thorac Oncol, 2021, 16(1):66-75. DOI:10.1016/j.jtho.2020.10.020.
[20] 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):e498-509. DOI:10.1016/S1470-2045(15)00007-8.