【肺常盘点】非小细胞肺癌免疫治疗进展一文览

生物_医药_科研 2019-08-16

展开全文

上周小编为大家汇总了肺癌常见靶点及靶向药物，今天我们就来对非小细胞肺癌的免疫治疗进展进行汇总，希望通过这一篇文章，能够让各位有所收获。

一

新辅助免疫治疗

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一项在未治、可切除的NSCLC（I- IIIA期）中开展的I期临床研究，术前给予2周期纳武利尤单抗治疗，主要研究终点是纳武利尤单抗在NSCLC新辅助治疗中安全性和可行性。结果证实，使用新辅助纳武利尤单抗治疗NSCLC毒性可控，不会导致手术延期。45%的接受手术切除的患者达到了病理学显著缓解率（MPR）。

LCMC3研究

一项II期研究,阿替利珠单抗用于初治可手术的IB-IIIA和选择性IIIB期NSCLC。该研究在2019年ASCO上更新了疗效的中期分析结果：MPR为19%，病理完全缓解（pCR）为5%；安全性也较好。

MK3475-223研究

一项单臂、I期、剂量递增和扩展队列试验，研究新辅助帕博利珠单抗治疗早期可切除NSCLC患者的安全性和可行性。2019年ASCO上更新的有限数据显示，4例患者获得MPR（4/10接受2周期帕博利珠单抗;40%;95% C.I. 16.7-68.8%）。

ChiCTR-OIC-17013726研究

这是一项在中国开展，旨在评估信迪利单抗单药用于可切除NSCLC新辅助治疗的开放性、单中心、Ib期研究，结果显示：45.5%的患者达到MPR，其中18.2%的患者达到了pCR。

NEOSTAR研究

一项II期临床研究，比较了纳武利尤单抗vs 纳武利尤单抗联合ipilimumab对I-IIIA期可手术切除的早期NSCLC患者的疗效。研究结果在2019ASCO会上公布，在总人群中，MPR+pCR的比例为25%，其中单药组为17%，联合组为33%。在手术切除患者中，总MPR+pCR为30%，单药组为19%，联合组为44%。

NADIM研究

首个在IIIA期NSCLC患者中探究免疫联合化疗新辅助治疗可手术患者疗效的多中心II期临床研究。入组患者首先接受3个周期纳武利尤单抗+紫杉醇+卡铂的治疗方案，术后继续以纳武利尤单抗维持治疗一年。第19届WCLC上，该研究的初步结果被公布，今年ASCO年会上则进一步公布了更新后的数据：MPR达到85.36%，71.4%的患者达到pCR。

阿替利珠单抗联合化疗研究

这项II期研究在2018年ASCO上公布了结果，给予 IB-IIIA期可切除NSCLC患者阿替利珠单抗+卡铂+紫杉醇进行两个周期的新辅助化疗后，50%的患者达到MPR提升到了，包括21.4%的患者达到pCR。

表1.免疫新辅助治疗在NSCLC的研究进展汇总

二

晚期NSCLC的一线免疫治疗

目前免疫治疗在NSCLC一线的探索主要集中在联合治疗方面，而且也有免疫治疗药物收获了一线NSCLC适应症：2019年3月28日，帕博利珠单抗联合培美曲塞和铂类化疗药物一线治疗EGFR基因突变阴性和ALK阴性的转移性非鳞NSCLC的适应症在国内正式获批。单药研究方面多针对PD-L1阳性NSCLC患者。由于免疫检查点抑制剂单药或联合的数据迅速发展，在晚期NSCLC一线治疗中，各种方法的搭配正在快速变化，现将免疫治疗在NSCLC一线的主要研究进展汇总如下：

表2. NSCLC一线免疫治疗主要研究进展汇总

三

晚期NSCLC的二线/后线免疫治疗

目前免疫治疗在NSCLC二线已有多个药物获批，纳武利尤单抗、帕博利珠单抗、阿替利珠单抗和Durvalumab分别是FDA和EMA批准的晚期NSCLC的二线治疗免疫药物。与标准多西他赛相比，这些药物显示出更高的客观反应率（ORR）、更长的OS和更好的毒性。在国内有二线适应症的免疫治疗药物是纳武利尤单抗，可用于治疗EGFR基因突变阴性和ALK阴性、既往接受过含铂方案化疗后疾病进展或不可耐受的局部晚期或转移性NSCLC成人患者。随着一线治疗和支持治疗的改善，进入二线治疗的人群在不断增加：分别有50-70%非鳞癌，40-60%鳞癌患者能够接受二线治疗，现将免疫治疗在NSCLC二线/后线的主要研究进展汇总如下：

表3. NSCLC二线/后线免疫治疗主要研究进展汇总

参考文献：

1. Forde PM, Chaft JE, Smith KN,et al. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986.

2. Kwiatkowski DJ, Rusch VW, Chaft JE,et al. Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Interim analysis and biomarker data from a multicenter study (LCMC3). 2019 ASCO meeting，Abstract 8503.

3. Bar J, Urban D, Ofek E,et al. Neoadjuvant pembrolizumab (Pembro) for early stage non-small cell lung cancer (NSCLC): Updated report of a phase I study, MK3475-223. 2019 ASCO meeting，Abstract 8534.

4. Li N, Ying JM, Tao XL,et al. Efficacy and safety of neoadjuvant PD-1 blockade with sintilimab in resectable squamous non-small cell lung cancer (sqNSCLC). 2019 ASCO meeting，Abstract 8531.

5. Cascone T, William WN, Weissferdt A,et al. Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): Clinical and correlative results from the NEOSTAR study.2019 ASCO meeting，Abstract 8504.

6. Provencio M, Nadal E, Insa A,et al. NEO-adjuvant chemo-immunotherapy for the treatment of STAGE IIIA resectable non-small-cell lung cancer (NSCLC): A phase II multicenter exploratory study—Final data of patients who underwent surgical assessment. 2019 ASCO meeting，Abstract 8509.

7. Shu CA, Grigg C, Chiuzan C,et al. Neoadjuvant atezolizumab + chemotherapy in resectable non-small cell lung cancer (NSCLC). 2018 ASCO meeting，Abstract 8532.

8. Garon EB, Hellmann MD, Costa EC,et al, Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001. 2019 ASCO meeting，Abstract LBA9015.

9.Reck M, Rodríguez-Abreu D, et al.Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833.

10. Mok TSK, Wu YL, Kudaba I,et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830.

11. Carbone DP, Reck M, Paz-Ares L,et al. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Jun 22;376(25):2415-2426.

12. Gadgeel SM, Garassino MC, Esteban E, et al.KEYNOTE-189: Updated OS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastatic nonsquamous NSCLC. 2019 ASCO meeting，Abstract 9013.

13. PPaz-Ares L, Luft A, Vicente D,et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051.

14. Ackermann CJ, Reck M, Paz-Ares L,et al. First-line immune checkpoint blockade for advanced non-small-cell lung cancer: Travelling at the speed of light. Lung Cancer. 2019 Aug;134:245-253.

15. Hellmann MD, Ciuleanu TE, Pluzanski A,et al.Nivolumab plus Ipilimumab in Lung Cancer

with a High Tumor Mutational Burden. N Engl J Med. 2018 May 31;378(22):2093-2104.

16. Herbs RS.Long-term survival in patients (pts) with advanced NSCLC in the KEYNOTE-010 study overall and in pts who completed 2 years of pembrolizumab (pembro). 2018 ESMO meeting，LBA63.

17. Gettinger S, Horn L, Jackman D,et al. Five-Year Follow-Up of Nivolumab in Previously Treated Advanced Non-Small-Cell Lung Cancer: Results From the CA209-003 Study. J Clin Oncol. 2018 Jun 10;36(17):1675-1684.

18.Vokes EE, Ready N, Felip E,et al. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Ann Oncol. 2018 Apr 1;29(4):959-965.

19. Presented By Wu YL.2018 AACR Annual Meeting. abstract CT114.

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. Lancet. 2016 Apr 30;387(10030):1837-46.

21. Rittmeyer A, Barlesi F, Waterkamp D,et al.Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3,open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265.

22. Zhou C, Gao GH, Wang YN,et al. Efficacy of PD-1 monoclonal antibody SHR-1210 plus apatinib in patients with advanced non-squamous NSCLC with wild‐type EGFR and ALK.2019 ASCO meeting，Abstract 9112.

23. Saltos AN,Tanvetyanon T,Haura EB,et al. Phase I/Ib study of pembrolizumab and vorinostat in patients with metastatic NSCLC (mNSCLC): Updated results. 2019 ASCO meeting，Abstract 9073.

24. Felip E, Brunsvig P, Vinolas N,et al. A phase II study of bemcentinib (BGB324), a first-in-class highly selective AXL inhibitor, with pembrolizumab in pts with advanced NSCLC: OS for stage I and preliminary stage II efficacy. 2019 ASCO meeting，Abstract 9098.

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