Полный радиологический ответ при использовании пембролизумаба в монорежиме во 2-й линии лекарственной терапии MSI-h / dMMR-положительного распространенного рака эндометрия. Клинический случай
https://doi.org/10.17650/2949-5857-2023-13-3-49-56
Аннотация
До недавнего времени прогноз больных распространенным раком эндометрия, несмотря на проводимые стандартные методы лечения, оставался неутешительным. Ни один из препаратов в арсенале онкологов-химиотерапевтов не обеспечивал долговременного контроля болезни и длительной выживаемости пациенток, получивших стандартную платиносодержащую химиотерапию 1-й линии. Очевидно, что неудовлетворительные результаты лечения больных распространенным раком эндометрия требовали изменения подходов к терапии и указывали на необходимость разработки более эффективных режимов лечения. Углубленное понимание механизмов канцерогенеза, появление новой молекулярной классификации рака эндометрия и разделение лечебных подходов в зависимости от биологического потенциала опухоли привели к значительному прорыву в лечении распространенного рака эндометрия. Одним из наиболее важных достижений следует считать открытие роли микросателлитной нестабильности (MSI) и нарушений в системе репарации неспаренных оснований дезоксирибонуклеиновой кислоты (MMR) как предиктора высокой эффективности иммунотерапии – нового направления системной лекарственной терапии распространенного рака эндометрия. В статье представлен клинический случай успешного лечения MSI-h / dMMR-положительного распространенного рака эндометрия с использованием в качестве лекарственной терапии 2-й линии (при наличии рефрактерности к стандартной платиносодержащей химиотерапии 1-й линии) пембролизумаба в монорежиме с достижением полного радиологического ответа опухоли на лечение.
Ключевые слова
Об авторах
А. Д. ДаренскаяРоссия
Анна Дмитриевна Даренская
115522 Москва, Каширское шоссе, 24
Б. М. Медведева
Россия
115522 Москва, Каширское шоссе, 24
А. А. Румянцев
Россия
115522 Москва, Каширское шоссе, 24
А. С. Тюляндина
Россия
115522 Москва, Каширское шоссе, 24
119991 Москва, ул. Трубецкая, 8, стр. 2
Список литературы
1. Состояние онкологической помощи населению России в 2021 году. Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2022. 239 с.
2. Злокачественные новообразования в России в 2021 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2022. 252 с.
3. Miller D.S., Filiaci V.L., Mannel R.S. et al. Carboplatin and paclitaxel for advanced endometrial cancer: final overall survival and adverse event analysis of a phase III trial (NRG Oncology/ GOG0209). J Clin Oncol 2020;38(33):3841–50. DOI: 10.1200/JCO.20.01076
4. Miller D., Filiaci V., Fleming G. et al. Late-breaking abstract 1: Randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2012;125(3):771. DOI: 10.1016/j.ygyno.2012.03.034
5. Нечушкина В.М., Коломиец Л.А., Кравец О.А. и др. Практические рекомендации по лекарственному лечению рака тела матки и сарком матки. Злокачественные опухоли: Практические рекомендации RUSSCO #3s2, 2022;12(3):260–75. DOI: 10.18027/2224-5057-2022-12-3s2-260-275
6. National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Uterine Neoplasms. Version 1.2023. December 22, 2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf
7. Lorusso D., Ferrandina G., Colombo N. et al. Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III–IV) or recurrent endometrial cancer: The MITO END-2 trial. J Clin Oncol 2015;33 (15 Suppl): 5502. DOI: 10.1200/jco.2015.33.15_suppl.5502
8. Аghajanian C., Filiaci V.L., Dizon D.S. et al. A randomized phase II study of paclitaxel/carboplatin/ bevacizumab, paclitaxel/ carboplatin/temsirolimus and ixabepilone/carboplatin/ bevacizumab as initial therapy for measurable stage III or IVA, stage IVB or recurrent endometrial cancer, GOG-86P. J Clin Oncol 2015;33(Suppl): Abstract 5500.
9. Fader A.N., Roque D.M., Siegel E. et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol 2018;36(20):2044–51. DOI: 10.1200/JCO.2017.76.5966
10. Lincoln S., Blessing J.A., Lee R.B. et al. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: a gynecologic oncology group study. Gynecol Oncol 2003;88(3):277–81. DOI: 10.1016/S0090-8258(02)00068-9
11. Homesley H.D., Meltzer N.P., Nieves L. et al. A phase II trial of weekly 1-hour paclitaxel as second-line therapy for endometrial and cervical cancer. Int J Clin Oncol 2008;13(1):62–5. DOI: 10.1007/s10147-007-0731-5
12. Garcia A.A., Blessing J.A., Nolte S. et al. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: A study by the Gynecologic Oncology Group. Gynecol Oncol 2008;111(1):22–6. DOI: 10.1016/j.ygyno.2008.06.013
13. Tait D.L., Blessing J.A., Hoffman J.S. et al. A phase II study of gemcitabine (gemzar, LY188011) in the treatment of recurrent or persistent endometrial carcinoma: A gynecologic oncology group study. Gynecol Oncol 2011;121(1):118–2. DOI: 10.1016/j.ygyno.2010.11.027
14. Fracasso P.M., Blessing J.A., Molpus K.L. et al. Phase II study of oxaliplatin as second-line chemotherapy in endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2006;103(2):523–6. DOI: 10.1016/j.ygyno.2006.03.043
15. Makker V., Hensley M.L., Zhou Q. et al. Treatment of Advanced or Recurrent Endometrial Carcinoma with Doxorubicin in Patients Progressing After Paclitaxel/Carboplatin: Memorial Sloan-Kettering Cancer Center Experience From 1995 to 2009. Int J Gynecol Cancer 2013;23(5):929–34. DOI: 10.1097/IGC.0b013e3182915c20
16. Moreira E., Paulino E., Ingles Garces Á.H. et al. Efficacy of doxorubicin after progression on carboplatin and paclitaxel in advanced or recurrent endometrial cancer: a retrospective analysis of patients treated at the Brazilian National Cancer Institute (INCA). Med Oncol 2018;35(3):20. DOI: 10.1007/s12032-018-1086-7
17. Muggia F.M., Blessing J.A., Sorosky J. et al. Phase II Trial of the Pegylated Liposomal Doxorubicin in Previously Treated Metastatic Endometrial Cancer: A Gynecologic Oncology Group Study. J Clin Oncol 2002;20(9):2360–4. DOI:10.1200/JCO.2002.08.171
18. Sutton G.P., Blessing J.A., Homesley H.D. et al. Phase II study of ifosfamide and mesna in refractory adenocarcinoma of the endometrium. A Gynecologic Oncology Group study. Cancer 1994;73(5):1453–5. DOI: 10.1002/1097-0142(19940301)73:5<1453:aid-cncr2820730521>3.0.co;2-x
19. Rose P.G., Blessing J.A., Lewandowski G.S. et al. A phase II trial of prolonged oral etoposide (VP-16) as second-line therapy for advanced and recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 1996;63(1):101–4. DOI: 10.1006/gyno.1996.0286
20. Miller D.S., Blessing J.A., Lentz S.S. et al. A Phase II Trial of Topotecan in Patients with Advanced, Persistent, or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study. Gynecol Oncol 2002;87(3):247–51. DOI: 10.1006/gyno.2002.6804
21. Miller D.S., Blessing J.A., Drake R.D. et al. A phase II evaluation of pemetrexed (Alimta, LY231514, IND #40061) in the treatment of recurrent or persistent endometrial carcinoma: a phase II study of the Gynecologic Oncology. Gynecol Oncol 2009;115(3):443–6. DOI: 10.1016/j.ygyno.2009.09.004
22. Dizon D.S., Blessing J.A., McMeekin D.S. et al. Phase II trial of ixabepilone as second-line treatment in advanced endometrial cancer: Gynecologic Oncology Group trial 129-P. J Clin Oncol 2009;27(19):3104–8. DOI: 10.1200/JCO.2008.20.6995
23. Markman M., Fowler J. Activity of weekly paclitaxel in patients with advanced endometrial cancer previously treated with both a platinum agent and paclitaxel. Gynecol Oncol 2004;92(1):180–2. DOI: 10.1016/j.ygyno.2003.10.019
24. Moore K.N., Tian C., McMeekin S. et al. Does the progression-free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer? Cancer 2010;116(23):5407–14. DOI: 10.1002/cncr.25480
25. Nagao S., Nishio S., Michimae H. et al. Applicability of the concept of “platinum sensitivity” to recurrent endometrial cancer: The SGSG-012/GOTIC-004/Intergroup study. Gynecol Oncol 2013;131(3):567–73. DOI: 10.1016/j.ygyno.2013.09.021
26. Slomovitz B.M., Jiang Y., Yates M.S. et al. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol 2015;33(8):930–6. DOI: 10.1200/JCO.2014.58.3401
27. Coleman R.L., Sill M.W., Lankes H.A. et al. A phase II evaluation of aflibercept in the treatment of recurrent or persistent endometrial cancer: A Gynecologic Oncology Group study. Gynecol Oncol 2012;127(3):538–43. DOI: 10.1016/j.ygyno.2012.08.020
28. Makker V., Filiaci V.L., Chen L.M. et al. Phase II evaluation of dalantercept, a soluble recombinant activin receptor-like kinase 1 (ALK1) receptor fusion protein, for the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study 0229N. Gynecol Oncol 2015;138(1):24–9. DOI: 10.1016/j.ygyno.2015.04.006
29. Aghajanian C., Sill M.W., Darcy K.M. et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: A Gynecologic Oncology Group study. J Clin Oncol 2011;29(16):2259–65. DOI: 10.1200/JCO.2010.32.6397
30. Castonguay V., Lheureux S., Welch S. et al. A phase II trial of sunitinib in women with metastatic or recurrent endometrial carcinoma: A study of the Princess Margaret, Chicago and California Consortia. Gynecol Oncol 2014;134(2):274–80. DOI: 10.1016/j.ygyno.2014.05.016
31. Nimeiri H.S., Oza A.M., Morgan R.J. et al. A phase II study of sorafenib in advanced uterine carcinoma/carcinosarcoma: A trial of the Chicago, PMH, and California Phase II Consortia. Gynecol Oncol 2010;117(1):37–40. DOI: 10.1016/j.ygyno.2010.01.013
32. Powell M.A., Sill M.W., Goodfellow P.J. et al. A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study. Gynecol Oncol 2014;135(1):38–43. DOI: 10.1016/j.ygyno.2014.07.083
33. Dizon D.S, Sill M.W., Schilder J.M. et al. A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study. Gynecol Oncol 2014;135(3):441–5. DOI: 10.1016/j.ygyno.2014.10.001
34. Bender D., Sill M.W., Lankes H.A. et al. A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol 2015;138(3):507–12. DOI: 10.1016/j.ygyno.2015.07.018
35. Moore K.N., Sill M.W., Tenney M.E. et al. A phase II trial of trebananib (AMG 386; IND#111071), a selective angiopoietin 1/2 neutralizing peptibody, in patients with persistent/ recurrent carcinoma of the endometrium: An NRG/Gynecologic Oncology Group trial. Gynecol Oncol 2015;138(3):513–8. DOI: 10.1016/j.ygyno.2015.07.006
36. Leslie K.K., Sill M.W., Fischer E. et al. A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study. Gynecol Oncol 2013;129(3):486–94. DOI: 10.1016/j.ygyno.2013.02.019
37. Oza A.M., Eisenhauer E.A., Elit L. et al. Phase II study of erlotinib in recurrent or metastatic endometrial cancer: NCIC IND-148. J Clin Oncol 2008;26(26):4319–25. DOI: 10.1200/JCO.2007.15.8808
38. Slomovitz В.M., Chelariu-Raicu А., Schmeler K.M. et al. Phase 2 study of cetuximab (Erbitux) in patients with progressive or recurrent endometrial cancer. Int J Gynecol Cancer 2020;30(11):1733–7. DOI: 10.1136/ijgc-2020-001859
39. Fleming G.F., Sill M.W., Darcy K.M. et al. Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2010;116(1):15–20. DOI: 10.1016/j.ygyno.2009.09.025
40. Leslie K.K., Sill M.W., Lankes H.A. et al. Lapatinib and potential prognostic value of EGFR mutations in a Gynecologic Oncology Group phase II trial of persistent or recurrent endometrial cancer. Gynecol Oncol 2012;127(2):345–50. DOI: 10.1016/j.ygyno.2012.07.127
41. Slomovitz B.M., Lu K.H., Johnston T. et al. A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma. Cancer 2010;116(23):5415–9. DOI: 10.1002/cncr.25515
42. Ray-Coquard I., Favier L., Weber B. et al. Everolimus as second- or third-line treatment of advanced endometrial cancer: ENDORAD, a phase II trial of GINECO. Br J Cancer 2013;108(9):1771–7. DOI: 10.1038/bjc.2013.183
43. Oza A.M., Elit L., Tsao M.S. et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: A trial of the NCIC Clinical Trials Group. J Clin Oncol 2011;29(24):3278–85. DOI: 10.1200/JCO.2010.34.1578
44. Fleming G.F., Filiaci V.L., Marzullo B. et al. Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: A Gynecologic Oncology Group study. Gynecol Oncol 2014;132(3):585–92. DOI: 10.1016/j.ygyno.2014.01.015
45. Colombo N., McMeekin D.S., Schwartz P.E. et al. Ridaforolimus as a single agent in advanced endometrial cancer: Results of a single-arm, phase 2 trial. Br J Cancer 2013;108(5):1021–6. DOI: 10.1038/bjc.2013.59
46. Oza A.M., Pignata S., Poveda A. et al. Randomized phase II trial of ridaforolimus in advanced endometrial carcinoma. J Clin Oncol 2015;33(31):3576–82. DOI: 10.1200/JCO.2014.58.8871
47. Alvarez E.A., Brady W.E., Walker J.L. et al. Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2013;129(1):22–7. DOI: 10.1016/j.ygyno.2012.12.022
48. Lorenzi M., Amonkar M., Zhang J. et al. Epidemiology of Microsatellite Instability High (MSI-H) and Deficient Mismatch Repair (dMMR) in Solid Tumors: A Structured Literature Review. J Oncol 2020;2020:1–17. DOI:10.1155/2020/1807929
49. Marabelle A., Fakih M., Lopez J. 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 2020;21(10):1353–65. DOI: 10.1016/S1470-2045(20)30445-9
50. Le D.T., Uram J.N., Wang H. et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372(26):2509–20. DOI: 10.1056/NEJMoa1500596
51. Marabelle A., Le D.T., Ascierto P.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 2020;38(1):1–10. DOI: 10.1200/JCO.19.02105
52. Keytruda (pembrolizumab) [package insert]. Whitehouse Station, NJ, Merck Sharp & Dohme, 2018.
53. Arora E., Masab M., Mittar P. et al. Role of immune checkpoint inhibitors in advanced or recurrent endometrial cancer. Cureus 2018;10:e2521.
54. Diaz L.A., Marabelle A., Delord J.P. et al. Pembrolizumab therapy for microsatellite instability high (MSI-H) colorectal cancer (CRC) and non-CRC. J Clin Oncology 2017;35(15):3071. DOI: 10.1200/JCO.2017.35.15_suppl.3071
55. O’Malley D.M., Bariani G.M., Cassier P.A. et al. Pembrolizumab in patients with microsatellite instability-high advanced endometrial cancer: results from the KEYNOTE-158 study. J Clin Oncol 2022;40(7):752–61. DOI: 10.1200/JCO.21.01874
56. Lee C.-H., Shah A.Y., Hsieh J.J. et al. Phase II trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) for disease progression after PD-1/PD-L1 immune checkpoint inhibitor (ICI) in metastatic clear cell renal cell carcinoma (mccRCC). J Clin Oncol 2020;38(15 Suppl): abstr 5008. DOI: 10.1200/JCO.2020.38.15_suppl.5008