臨床婦人科産科77巻9号

2023年09月発行

今月の臨床 専攻医必携！　免疫チェックポイント阻害薬が変える子宮がん診療

総論

子宮悪性腫瘍に対する免疫チェックポイント阻害薬の適応の変遷

著者： 山本香澄¹ 西川忠曉¹ 米盛勧¹

所属機関： ¹国立がん研究センター中央病院腫瘍内科

ページ範囲：P.860 - P.866

文献概要

●MSI-HighまたはTMB-Highを有する婦人科がんに対してペムブロリズマブが有効である．

●2021年12月に，プラチナ製剤を含むがん化学療法後に増悪した進行・再発子宮体がんに対して，マイクロサテライトの安定性に関係なく，ペムブロリズマブとレンバチニブの併用療法が保険適用となった．

●2022年9月に，進行・再発子宮頸がんの一次治療として，殺細胞性抗がん薬±血管新生阻害薬とペムブロリズマブの併用・維持療法が保険適用となった．

参考文献

1）Zhang L, et al : Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348 : 203-213, 2003

2）Curiel TJ, et al : Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10 : 942-949, 2004

3）Cancer Genome Atlas Research Network；Kandoth C, et al : Integrated genomic characterization of endometrial carcinoma. Nature 497 : 67-73, 2013

4）Talhouk A, et al : A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer 113 : 299-310, 2015

5）Le DT, et al : PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372 : 2509-2520, 2015

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

7）Le DT, et al : Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357 : 409-413, 2017

8）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

9）Marabelle A, et al : Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab : prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 21 : 1353-1365, 2020

10）Makker V, et al : Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer : an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 20 : 711-718, 2019

11）Makker V, et al : Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol 38 : 2981-2992, 2020

12）Makker V, et al : Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med 386 : 437-448, 2022

13）Bellone S, et al : A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high（MSI-H）endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics（NCT02899793）. Ann Oncol 32 : 1045-1046, 2021

14）Green AK, et al : A review of immune checkpoint blockade therapy in endometrial cancer. Am Soc Clin Oncol Educ Book 40 : 1-7, 2020

15）Mirza M, et al : Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med, 2023（in press）

16）Eskander RN, et al : Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med, 2023（in press）

17）Chen Z, et al : Elevated expression of programmed death-1 and programmed death ligand-1 negatively regulates immune response against cervical cancer cells. Mediators Inflamm 2016 : 6891482, 2016

18）Alexandrov LB, et al : Signatures of mutational processes in human cancer. Nature 500 : 415-421, 2013

19）Meng Y, et al : PD-L1 expression correlates with tumor infiltrating lymphocytes and response to neoadjuvant chemotherapy in cervical cancer. J Cancer 9 : 2938-2945, 2018

20）Feng YC, et al : The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance. Cancer Manag Res 10 : 105-113, 2018

21）Chung HC, et al : Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer : results from the phase II KEYNOTE-158 study. J Clin Oncol 37 : 1470-1478, 2019

22）Contos G, et al : Assessment of immune biomarkers and establishing a triple negative phenotype in gynecologic cancers. Gynecol Oncol 163 : 312-319, 2021

23）Colombo N, et al : Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med 385 : 1856-1867, 2021

24）Tewari KS, et al : Survival with cemiplimab in recurrent cervical cancer. N Engl J Med 386 : 544-555, 2022