放疗联合CDK4/6抑制剂治疗转移性乳腺癌的进展

doi:10.3760/cma.j.cn371439-20201222-00121

摘要/Abstract

摘要：

周期蛋白依赖性激酶4/6(CDK)4/6抑制剂是一类新型分子靶向药物,可通过抗血管生成、抑制DNA损伤修复以及抑制哺乳动物雷帕霉素靶蛋白信号转导起到放疗增敏作用。现有临床试验证实放疗联合CDK4/6抑制剂可有效控制乳腺癌转移病灶的局部症状,延长无进展生存期,且与单独使用CDK4/6抑制剂相比,联合治疗并未明显增加不良反应的发生率及严重程度;但也有联合治疗的个例发生放射野内正常组织严重不良反应的报道,其疗效与安全性尚需更多基础研究和临床研究加以明确。

关键词: 乳腺肿瘤, 周期素依赖激酶抑制蛋白质类, 放射疗法

Abstract:

Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of molecular targeted drugs, which can enhance radiotherapy sensitivity by anti angiogenesis, inhibiting DNA damage repair and inhibiting mammalian target of rapamycin signal transduction. Existing clinical trials have confirmed that radiotherapy combined with CDK4/6 inhibitors can effectively control the local symptoms of breast cancer metastases and prolong progression-free survival. Compared with CDK4/6 inhibitors alone, the combination with radiotherapy does not significantly increase the incidence and severity of adverse reactions. However, there are also reports about severe adverse reactions of normal tissue happened in the radiation field in individual cases of combined treatment, and its efficacy and safety need to be clarified by more basic and clinical observational researches.

Key words: Breast neoplasms, Cyclin-dependent kinase inhibitor proteins, Radiotherapy

杨宜婷, 徐晓婷. 放疗联合CDK4/6抑制剂治疗转移性乳腺癌的进展[J]. 国际肿瘤学杂志, 2021, 48(10): 618-621.

Yang Yiting, Xu Xiaoting. Research progress of radiotherapy and CDK4/6 inhibitors in metastatic breast cancer[J]. Journal of International Oncology, 2021, 48(10): 618-621.

参考文献 30

[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(3):209-249. DOI: 10.3322/caac.21660. doi: 10.3322/caac.21660
[2]	Gong Y, Liu YR, Ji P, et al. Impact of molecular subtypes on metastatic breast cancer patients: a SEER population-based study[J]. Sci Rep, 2017, 7:45411. DOI: 10.1038/srep45411. doi: 10.1038/srep45411 pmid: 28345619
[3]	Preusser M, De Mattos-Arruda L, Thill M, et al. CDK4/6 inhibitors in the treatment of patients with breast cancer: summary of a multidisciplinary round-table discussion[J]. ESMO Open, 2018, 3(5):e000368. DOI: 10.1136/esmoopen-2018-000368. doi: 10.1136/esmoopen-2018-000368
[4]	Fu W, Sun H, Zhao Y, et al. Trends and outcomes of neoadjuvant radiotherapy compared with postoperative radiotherapy for malignant breast cancer[J]. Oncotarget, 2018, 9(36):24525-24536. DOI: 10.18632/oncotarget.24313. doi: 10.18632/oncotarget.24313
[5]	Wei L, Leibowitz BJ, Wang X, et al. Inhibition of CDK4/6 protects against radiation-induced intestinal injury in mice[J]. J Clin Invest, 2016, 126(11):4076-4087. DOI: 10.1172/JCI88410. doi: 10.1172/JCI88410
[6]	Meattini I, Desideri I, Scotti V, et al. Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic breast cancer[J]. Breast, 2018, 42:1-2. DOI: 10.1016/j.breast.2018.08.096. doi: S0960-9776(18)30239-X pmid: 30118901
[7]	Naz S, Cook JA, Mitchell JB. Abemaciclib: a multi-functional radiation modifier[J]. Oncotarget, 2019, 10(12):1230-1232. DOI: 10.18632/oncotarget.26652. doi: 10.18632/oncotarget.26652
[8]	Guerini AE, Pedretti S, Salah E, et al. A single-center retrospective safety analysis of cyclin-dependent kinase 4/6 inhibitors concurrent with radiation therapy in metastatic breast cancer patients[J]. Sci Rep, 2020, 10(1):13589. DOI: 10.1038/s41598-020-70430-2. doi: 10.1038/s41598-020-70430-2
[9]	Cali Daylan AE, Leone JP. Targeted therapies for breast cancer brain metastases[J]. Clin Breast Cancer, 2021, 21(4):263-270. DOI: 10.1016/j.clbc.2020.11.014. doi: 10.1016/j.clbc.2020.11.014
[10]	Naz S, Sowers A, Choudhuri R, et al. Abemaciclib, a selective CDK4/6 inhibitor, enhances the radiosensitivity of non-small cell lung cancer in vitro and in vivo[J]. Clin Cancer Res, 2018, 24(16):3994-4005. DOI: 10.1158/1078-0432.CCR-17-3575. doi: 10.1158/1078-0432.CCR-17-3575
[11]	Xie X, Zheng W, Chen T, et al. CDK4/6 inhibitor palbociclib amplifies the radiosensitivity to nasopharyngeal carcinoma cells via mediating apoptosis and suppressing DNA damage repair[J]. Onco Targets Ther, 2019, 12:11107-11117. DOI: 10.2147/OTT.S234221. doi: 10.2147/OTT.S234221
[12]	Hashizume R, Zhang A, Mueller S, et al. Inhibition of DNA damage repair by the CDK4/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth[J]. Neuro Oncol, 2016, 18(11):1519-1528. DOI: 10.1093/neuonc/now106. doi: 10.1093/neuonc/now106
[13]	Das A, Alshareef M, Martinez Santos JL, et al. Evaluating anti-tumor activity of palbociclib plus radiation in anaplastic and radiation-induced meningiomas: pre-clinical investigations[J]. Clin Transl Oncol, 2020, 22(11):2017-2025. DOI: 10.1007/s12094-020-02341-7. doi: 10.1007/s12094-020-02341-7
[14]	Figura NB, Potluri TK, Mohammadi H, et al. CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases[J]. J Neurooncol, 2019, 144(3):583-589. DOI: 10.1007/s11060-019-03260-6. doi: 10.1007/s11060-019-03260-6
[15]	Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer[J]. N Engl J Med, 2016, 375(18):1738-1748. DOI: 10.1056/NEJMoa1609709. doi: 10.1056/NEJMoa1609709
[16]	Abraham J, Coleman R, Elias A, et al. Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive, human epidermal growth factor receptor 2-negative, metastatic breast cancer: a roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG)[J]. Breast Cancer Res Treat, 2018, 171(1):11-20. DOI: 10.1007/s10549-018-4783-1. doi: 10.1007/s10549-018-4783-1
[17]	Ippolito E, Greco C, Silipigni S, et al. Concurrent radiotherapy with palbociclib or ribociclib for metastatic breast cancer patients: preli-minary assessment of toxicity[J]. Breast, 2019, 46:70-74. DOI: 10.1016/j.breast.2019.05.001. doi: S0960-9776(19)30495-3 pmid: 31100573
[18]	Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial[J]. Lancet Oncol, 2016, 17(4):425-439. DOI: 10.1016/S1470-2045(15)00613-0. doi: S1470-2045(15)00613-0 pmid: 26947331
[19]	Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer[J]. N Engl J Med, 2016, 375(20):1925-1936. DOI: 10.1056/NEJMoa1607303. doi: 10.1056/NEJMoa1607303
[20]	Patnaik A, Rosen LS, Tolaney SM, et al. Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors[J]. Cancer Discov, 2016, 6(7):740-753. DOI: 10.1158/2159-8290.CD-16-0095. doi: 10.1158/2159-8290.CD-16-0095 pmid: 27217383
[21]	Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH 1, a phase Ⅱ study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR(+)/HER2(-) metastatic breast cancer[J]. Clin Cancer Res, 2017, 23(17):5218-5224. DOI: 10.1158/1078-0432.CCR-17-0754. doi: 10.1158/1078-0432.CCR-17-0754 pmid: 28533223
[22]	Beddok A, Xu HP, Henry AA, et al. Concurrent use of palbociclib and radiation therapy: single-centre experience and review of the literature[J]. Br J Cancer, 2020, 123(6):905-908. DOI: 10.1038/s41416-020-0957-9. doi: 10.1038/s41416-020-0957-9
[23]	Hans S, Cottu P, Kirova YM. Preliminary results of the association of palbociclib and radiotherapy in metastatic breast cancer patients[J]. Radiother Oncol, 2018, 126(1):181. DOI: 10.1016/j.radonc.2017.09.010. doi: 10.1016/j.radonc.2017.09.010
[24]	Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer[J]. J Clin Oncol, 2017, 35(32):3638-3646. DOI: 10.1200/JCO.2017.75.6155. doi: 10.1200/JCO.2017.75.6155
[25]	Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR⁺/HER2^- advanced breast cancer who had progressed while receiving endocrine therapy[J]. J Clin Oncol, 2017, 35(25):2875-2884. DOI: 10.1200/JCO.2017.73.7585. doi: 10.1200/JCO.2017.73.7585
[26]	O'shaughnessy J, Petrakova K, Sonke GS, et al. Ribociclib plus letrozole versus letrozole alone in patients with de novo HR⁺, HER2^- advanced breast cancer in the randomized MONALEESA-2 trial[J]. Breast Cancer Res Treat, 2018, 168(1):127-134. DOI: 10.1007/s10549-017-4518-8. doi: 10.1007/s10549-017-4518-8
[27]	Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial[J]. Lancet Oncol, 2018, 19(7):904-915. DOI: 10.1016/S1470-2045(18)30292-4. doi: S1470-2045(18)30292-4 pmid: 29804902
[28]	Chowdhary M, Sen N, Chowdhary A, et al. Safety and efficacy of palbociclib and radiation therapy in patients with metastatic breast cancer: initial results of a novel combination[J]. Adv Radiat Oncol, 2019, 4(3):453-457. DOI: 10.1016/j.adro.2019.03.011. doi: 10.1016/j.adro.2019.03.011 pmid: 31360799
[29]	Kawamoto T, Shikama N, Sasai K. Severe acute radiation-induced enterocolitis after combined palbociclib and palliative radiotherapy treatment[J]. Radiother Oncol, 2019, 131:240-241. DOI: 10.1016/j.radonc.2018.09.020. doi: 10.1016/j.radonc.2018.09.020
[30]	Messer JA, Ekinci E, Patel TA, et al. Enhanced dermatologic toxicity following concurrent treatment with palbociclib and radiation therapy: a case report[J]. Rep Pract Oncol Radiother, 2019, 24(3):276-280. DOI: 10.1016/j.rpor.2019.03.001. doi: 10.1016/j.rpor.2019.03.001