臨床婦人科産科74巻3号

2020年04月発行

今月の臨床 徹底解説！ 卵巣がんの最新治療―複雑化する治療を整理する

新規治療薬の作用機序と使いどころ《分子標的薬・免疫チェックポイント阻害薬》

免疫チェックポイント阻害薬の作用機序と使いどころ

著者： 濵西潤三¹ 万代昌紀¹

所属機関： ¹京都大学医学部附属病院産科婦人科

ページ範囲：P.344 - P.355

文献概要

●高頻度マイクロサテライト不安定性（MSI-High）の卵巣がんに対して，ペムブロリズマブは有効である．

●PARP阻害薬や血管新生阻害薬との併用療法が期待されている．

●特定の希少組織型に対する有用性も報告されている．

参考文献

1）Ishida Y, et al : Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 11 : 3887-3895, 1992

2）Iwai Y, et al : Cancer immunotherapies targeting the PD-1 signaling pathway. J Biomed Sci 24 : 26, 2017（doi : 10.1186/s12929-017-0329-9）, Review.

3）Okazaki T, et al : PD-1 and PD-1 ligands : from discovery to clinical application. Int Immunol 19 : 813-824, 2007

4）Hamanishi J, et al : PD-1/PD-L1 blockade in cancer treatment : perspectives and issues. Int J Clin Oncol 21 : 462-473, 2016

5）Hamanishi J, et al : Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. J Clin Oncol 33 : 4015-4022, 2015

6）Jelinic P, et al : Immune-Active Microenvironment in Small Cell Carcinoma of the Ovary, Hypercalcemic Type : Rationale for Immune Checkpoint Blockade. J Natl Cancer Inst 110 : 787-790, 2018

7）Burger R, et al : NRG Oncology phase II randomized trial of nivolumab with or without ipilimumab in patients with persistent or recurrent ovarian cancer. 17th Biennial Meeting of the International Gynecological Cancer Society ; September 14-16, 2018 ; Kyoto, Japan. Abstract OC11（https://www.targetedonc.com/publications/targeted-therapy-news/2018/oct-2018/io-combo-shows-potential-in-persistent-ovarian-cancer）

8）Matulonis UA, et al : Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer : results from the phase II KEYNOTE-100 study. Ann Oncol 30 : 1080-1087, 2019

9）Marabelle A, et al : Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer : Results From the Phase II KEYNOTE-158 Study. J Clin Oncol 38 : 1-10, 2020

10）Moore KN, et al : Safety and Activity of Mirvetuximab Soravtansine（IMGN853），a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer : A Phase I Expansion Study. J Clin Oncol 35 : 1112-1118, 2017

11）Konstantinopoulos PA, et al : Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma. JAMA Oncol : 13, 2019

12）O'Malley DM, et al : Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha（FRα）-targeting antibody-drug conjugate（ADC），in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecol Oncol : 18, 2020

13）Matulonis UA, et al : Phase II Study of Pembrolizumab（pembro）Combined With Pegylated Liposomal Doxorubicin（PLD）For Recurrent Platinum Resistant Ovarian, Fallopian Tube Or Peritoneal Cancer. SGO Annual Meeting on Woman's Cancer Scientific Plenary VI Mar 27 2018（https://sgo.confex.com/sgo/2018/meetingapp.cgi/Paper/10157）

14）Mitchell TC, et al : Epacadostat Plus Pembrolizumab in Patients With Advanced Solid Tumors : Phase I Results From a Multicenter, Open-Label Phase I/II Trial（ECHO-202/KEYNOTE-037）. J Clin Oncol. 2018 Sep 28 : JCO2018789602

15）Desai J, et al : A phase I dose-escalation study of BGB-A317, an anti-programmed death-1（PD-1）mAb in patients with advanced solid tumors. J Clin Oncol 34（suppl ; abstr 3066）, 2016

16）Friedlander M, et al : Pamiparib in combination with tislelizumab in patients with advanced solid tumours : results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial. Lancet Oncol 20 : 1306-1315, 2019

17）Gao B, et al : Safety and antitumor activity of sitravatinib in combination with tislelizumab in patients with advanced solid tumors : Ovarian cancer cohort data. Annals of Oncology 30（Issue Supplement_11）, December 2019

18）Pujade-LauraineaK E, et al : Avelumab alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in platinum-resistant or refractory epithelial ovarian cancer : Primary and biomarker analysis of the phase III JAVELIN Ovarian 200 trial. Gynecologic Oncology 154（Supplement 1）, 21-22, 2019

19）Drew Y, et al : An open-label, phase II basket study of olaparib and durvalumab（MEDIOLA）: Results in germline BRCA-mutated（gBRCAm）platinum-sensitive relapsed（PSR）ovarian cancer（OC）. SGO Annual Meeting on Women's health March 26, 2018 Late Breaking Abstracts

20）Lee JM, et al : Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in Combination With Poly（ADP-Ribose）Polymerase Inhibitor Olaparib or Vascular Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers : A Dose-Escalation, Phase I Study. J Clin Oncol 35 : 2193-2202, 2017

21）Drew Y, et al : Phase II study of olaparib＋durvalumab（MEDIOLA）: Updated results in germline BRCA-mutated platinum-sensitive relapsed（PSR）ovarian cancer（OC）. Annals of Oncology 30（Issue Supplement_5）, 2019

22）Liu JF, et al : Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in 22/recurrent ovarian and uterine cancers. Gynecol Oncol 154 : 314-322, 2019

23）Hamanishi J, et al : Specific gene signatures and oligo clonal expansion of B cell repertoire with responders of anti-PD-1 antibody, nivolumab for ovarian cancer : Novel predictive biomarkers. Specific gene signatures and oligo clonal expansion of b cell repertoire with responders of anti-PD-1 antibody, nivolumab for ovarian cancer : Novel predictive biomarkers. Journal of Clinical Oncology 34（15_suppl） : 5513, 2016

24）Oda K, et al : Genomics to immunotherapy of ovarian clear cell carcinoma : Unique opportunities for management. Gynecol Oncol 151 : 381-389, 2018

25）Bruno TC : New predictors for immunotherapy responses sharpen our view of the tumour microenvironment. Nature 577（7791） : 474-476, 2020

26）Xu W, et al : Pregnancy with successful foetal and maternal outcome in a melanoma patient treated with nivolumab in the first trimester : case report and review of the literature. Melanoma Res 29 : 333-337, 2019