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国际大咖说丨平衡毒性与疗效:ADC与其他疗法联合如何影响NSCLC的治疗前景?

作者:肿瘤瞭望   日期:2024/11/7 11:56:58  浏览量:103

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晚期非小细胞肺癌(NSCLC)的治疗策略包括铂类双药化疗、免疫疗法和靶向疗法,具体治疗手段取决于分子生物标志物的检测情况。晚期NSCLC患者目前尚未满足的医疗需求包括:接受免疫联合治疗失败后缺乏新的治疗选择,对靶向治疗产生耐药以及缺少改善疗效的策略。

晚期非小细胞肺癌(NSCLC)的治疗策略包括铂类双药化疗、免疫疗法和靶向疗法,具体治疗手段取决于分子生物标志物的检测情况。晚期NSCLC患者目前尚未满足的医疗需求包括:接受免疫联合治疗失败后缺乏新的治疗选择,对靶向治疗产生耐药以及缺少改善疗效的策略[1-3]
 
本文作者:
 
 
ADC是一种新兴药物,其治疗策略是向癌细胞递送强效的载荷,同时保护正常组织细胞,减少治疗相关不良事件(AE)并改善生活质量[4,5]。目前,许多最近研发的ADC正在NSCLC中进行探索,其安全性各不相同(表1)[6-10]
 
优化ADC安全性的可能策略包括设置剂量上限(dose-capping)、分次给药(fractionated administration)和设置治疗持续时间上限(capping of treatment duration)[11]
 
表1.NSCLC ADC试验中报告的最常见的任何级别AE和≥3级AE
 
限制用药周期数
 
“限制用药周期数”是历史上研究化疗的一种策略,因为需要权衡疗效与毒性。多项试验已证实,在施用更多化疗周期时,未观察到反应率、生存结果或生活质量的改善[12-16]
 
研究人员在接受polatuzumab vedotin(抗CD79b抗体,含有单甲基auristatin E有效载荷的ADC)的患者中进行了事件发生时间(time-to-event)分析,从而探索“限制用药周期数”的策略。分析显示,当最多施用6~8个治疗周期时,≥2级周围神经病变(报告的主要限制性不良事件)的发生率显著下降[17]
 
“至应答时间(Time-to-response)”对于确定ADC“适当的用药周期数”也有参考价值。进行这些研究将有助于我们确认“限制用药周期数”对降低毒性和保持疗效的影响。
 
ADC联合免疫/靶向疗法
 
此外,“将ADC与免疫疗法或靶向疗法相结合”是一种目前正在研究的策略,旨在提高疗效并克服/预防患者发生耐药。重要的是,一些试验是在一线NSCLC患者中进行的。表2展示了正在进行的将ADC与免疫疗法或靶向疗法相联合的试验。[18-21]
 
表2.ADC与免疫或靶向疗法相结合的NSCLC试验
 
对于接受ADC联合免疫/靶向治疗的患者,在患者接受足够数量的ADC治疗周期后继续进行维持性免疫或靶向治疗,这可能是一个有前景的选择,如下所示。
 
图1.诱导ADC联合免疫/靶向治疗,随后进行维持治疗的建议
 
总之,ADC的使用范围正在显著扩大,为免疫/靶向治疗失败的患者甚至一线NSCLC患者提供了可能的治疗选择。然而,ADC的应用过程也发现了新的药物毒性特征,需要找到减轻毒性的方法。“限制ADC给药次数,并将ADC与维持治疗结合使用”是值得探索的方向,以改善患者的生活质量。
 
参考文献
 
1.Hendriks LE,Kerr KM,Menis J,et al;ESMO Guidelines Committee.Non-oncogene-addicted metastatic non-small-cell lung cancer:ESMO Clinical Practice Guideline for diagnosis,treatment and follow-up.Ann Oncol.2023;34(4):358-376.
 
2.Hendriks LE,Kerr KM,Menis J,et al;ESMO Guidelines Committee.Oncogene-addicted metastatic non-small-cell lung cancer:ESMO Clinical Practice Guideline for diagnosis,treatment and follow-up.Ann Oncol.2023;34(4):339-357.
 
3.Meyer M,Fitzgerald B,Paz-Ares L,et al.New promises and challenges in the treatment of advanced non-small-cell lung cancer.Lancet.2024;404(10454):803-822.
 
4.Fu Z,Li S,Han S,Shi C,Zhang Y.Antibody drug conjugate:the“biological missile”for targeted cancer therapy.Signal Transduct Target Ther.2022;7(1):93.
 
5.Drago JZ,Modi S,Chandarlapaty S.Unlocking the potential of antibody-drug conjugates for cancer therapy.Nat Rev Clin Oncol.2021;18(6):327-344.
 
6.Goto K,Goto Y,Kubo T,et al.Trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small-cell lung cancer:primary results from the randomized,phase II DESTINY-Lung02 trial.J Clin Oncol.2023;41(31):4852-4863.
 
7.Paz-Ares LG,Juan-Vidal O,Mountzios GS,et al.Sacituzumab govitecan versus docetaxel for previously treated advanced or metastatic non-small-cell lung cancer:the randomized,open-label phase III EVOKE-01 study.J Clin Oncol.2024;42(24):2860-2872.
 
8.Ahn M,Lisberg A,Paz-Ares L,et al.LBA12 Datopotamab deruxtecan(Dato-DXd)vs docetaxel in previously treated advanced/metastatic(adv/met)non-small-cell lung cancer(NSCLC):results of the randomized phase III study TROPION-Lung01.Ann Oncol.2023;34:S1305-S1306.
 
9.Yu HA,Goto Y,Hayashi H,et al.HERTHENA-Lung01,a phase II trial of patritumab deruxtecan(HER3-DXd)in epidermal growth factor receptor-mutated non-small-cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitor and platinum-based chemotherapy.J Clin Oncol.2023;41(35):5363-5375.
 
10.Camidge DR,Bar J,Horinouchi H,et al.Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein-overexpressing advanced nonsquamous EGFR-wildtype non-small cell lung cancer in the phase II LUMINOSITY trial.J Clin Oncol.2024;42(25):3000-3011.
 
11.Tarantino P,Ricciuti B,Pradhan SM,Tolaney SM.Optimizing the safety of antibody-drug conjugates for patients with solid tumours.Nat Rev Clin Oncol.2023;20(8):558-576.
 
12.Socinski MA,Morris DE,Masters GA,Lilenbaum R;American College of Chest Physicians.Chemotherapeutic management of stage IV non-small cell lung cancer.Chest.2003;123(suppl 1):226S-243S.
 
13.Smith IE,O’Brien ME,Talbot DC,et al.Duration of chemotherapy in advanced non-small-cell lung cancer:a randomized trial of three versus six courses of mitomycin,vinblastine,and cisplatin.J Clin Oncol.2001;19(5):1336-1343.
 
14.Socinski MA,Schell MJ,Peterman A,et al.Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer.J Clin Oncol.2002;20(5):1335-1343.
 
15.Park JO,Kim SW,Ahn JS,et al.Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer.J Clin Oncol.2007;25(33):5233-5239.
 
16.Rossi A,Chiodini P,Sun JM,et al.Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer:a systematic review and meta-analysis of individual patient data.Lancet Oncol.2014;15(11):1254-1262.
 
17.Lu D,Gillespie WR,Girish S,et al.Time-to-event analysis of polatuzumab vedotin-induced peripheral neuropathy to assist in the comparison of clinical dosing regimens.CPT Pharmacometrics Syst Pharmacol.2017;6(6):401-408.
 
18.Iwata TN,Ishii C,Ishida S,Ogitani Y,Wada T,Agatsuma T.A HER2-targeting antibody–drug conjugate,trastuzumab deruxtecan(DS-8201a),enhances antitumor immunity in a mouse model.Mol Cancer Ther.2018;17(7):1494-1503.
 
19.Haratani K,Yonesaka K,Takamura S,et al.U3-1402 sensitizes HER3-expressing tumors to PD-1 blockade by immune activation.J Clin Invest.2020;130(1):374-388.
 
20.Goto Y,Su W,Levy B,et al.TROPION-Lung02:Datopotamab deruxtecan(Dato-DXd)plus pembrolizumab(pembro)with or without platinum chemotherapy(Pt-CT)in advanced non-small cell lung cancer(aNSCLC).J Clin Oncol.2023;41:16s(suppl;abstr 9004).
 
21.<jrn>Comer F,Mazor Y,Hurt E,et al.AZD9592:an EGFR-cMET bispecific antibody-drug conjugate(ADC)targeting oncogenic drivers in non-small-cell lung cancer(NSCLC)and beyond.Cancer Res.2023;83:7s(suppl;abstr 5736).

 

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