REVIEW PAPER
Dostarlimab as a promising immunotherapy for endometrial cancer treatment – literature review
1
Student Research Group / Physiology Department, Medical University, Lublin, Poland
2
Physiology Department, Medical University, Lublin, Poland
Corresponding author
J Pre Clin Clin Res. 2023;17(3):186-194
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
Endometrial cancer, a leading gynecological malignancy, is on the rise globally. Existing treatments for advanced cases have limited effectiveness and notable side-effects. Dostarlimab, a monoclonal antibody, enhances the immune response against tumuors by blocking the PD-1/PD-L1/PD-L2 interaction. This review examines dostarlimab’s role, mechanism, clinical trials, and safety in endometrial cancer
Review methods:
A search was conducted using PubMed and Google Scholar databases to evaluate dostarlimab’s therapeutic potential in endometrial cancer. The review encompasses studies detailing its mechanism of action, clinical trial outcomes, and safety data.
Brief description of the state of knowledge:
Endometrial cancer, the foremost gynecological malignancy in developed countries, has seen a surge in global incidence. Traditional treatments for advanced or recurrent cases exhibit limited efficacy and notable toxicity. Dostarlimab, an innovative monoclonal antibody, intervenes in the PD-1/PD-L1/PD-L2 axis, augmenting anti-tumour immune responses and fostering tumour regression. In April 2021, accelerated FDA approval was granted for dostarlimab in mismatch repair deficient recurrent or advanced endometrial cancer, post-platinum regimen. Subsequently, on 9 February 2023, FDA approval was extended to a broader patient cohort, encompassing those ineligible for curative surgery or radiation
Summary:
Dostarlimab, targeting PD-1/PD-L1/PD-L2, shows promise in treating advanced endometrial cancer. Mechanism, trials, and safety are explored. FDA approvals highlight its potential. Ongoing trials and combination therapies suggest a dynamic role in management. Dostarlimab offers renewed hope for patients.
Endometrial cancer, a leading gynecological malignancy, is on the rise globally. Existing treatments for advanced cases have limited effectiveness and notable side-effects. Dostarlimab, a monoclonal antibody, enhances the immune response against tumuors by blocking the PD-1/PD-L1/PD-L2 interaction. This review examines dostarlimab’s role, mechanism, clinical trials, and safety in endometrial cancer
Review methods:
A search was conducted using PubMed and Google Scholar databases to evaluate dostarlimab’s therapeutic potential in endometrial cancer. The review encompasses studies detailing its mechanism of action, clinical trial outcomes, and safety data.
Brief description of the state of knowledge:
Endometrial cancer, the foremost gynecological malignancy in developed countries, has seen a surge in global incidence. Traditional treatments for advanced or recurrent cases exhibit limited efficacy and notable toxicity. Dostarlimab, an innovative monoclonal antibody, intervenes in the PD-1/PD-L1/PD-L2 axis, augmenting anti-tumour immune responses and fostering tumour regression. In April 2021, accelerated FDA approval was granted for dostarlimab in mismatch repair deficient recurrent or advanced endometrial cancer, post-platinum regimen. Subsequently, on 9 February 2023, FDA approval was extended to a broader patient cohort, encompassing those ineligible for curative surgery or radiation
Summary:
Dostarlimab, targeting PD-1/PD-L1/PD-L2, shows promise in treating advanced endometrial cancer. Mechanism, trials, and safety are explored. FDA approvals highlight its potential. Ongoing trials and combination therapies suggest a dynamic role in management. Dostarlimab offers renewed hope for patients.
Derlatka K, Tasior J, Kulczycka M, Pasieczna W, Prendecka-Wróbel M. Dostarlimab as a promising immunotherapy for endometrial cancer
treatment. J Pre-Clin Clin Res. 2023; 17(3): 186–194. doi: 10.26444/jpccr/172403
REFERENCES (64)
1.
Alexa M, Hasenburg A, Battista MJ. The TCGA Molecular Classification of Endometrial Cancer and Its Possible Impact on Adjuvant Treatment Decisions. Cancers (Basel). 2021;13(6):1478. doi:10.3390/cancers13061478.
2.
Rousset-Rouviere S, Rochigneux P, Chrétien AS, et al. Endometrial Carcinoma: Immune Microenvironment and Emerging Treatments in Immuno-Oncology. Biomedicines. 2021;9(6):632. doi:10.3390/biomedicines9060632.
3.
Sun X, Zhang Y, Shen F, et al. The histological type of endometrial cancer is not associated with menopause status at diagnosis. Biosci Rep. 2022;42(3):BSR20212192. doi:10.1042/BSR20212192.
4.
Yen TT, Wang TL, Fader AN, Shih IM, Gaillard S. Molecular Classification and Emerging Targeted Therapy in Endometrial Cancer. Int J Gynecol Pathol. 2020;39(1):26–35. doi:10.1097/PGP.0000000000000585.
5.
Costa B, Vale N. Dostarlimab: A Review. Biomolecules. 2022;12(8):1031. doi:10.3390/biom12081031.
6.
Oaknin A, Gilbert L, Tinker AV, et al. Safety and antitumour activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. J Immunother Cancer. 2022;10(1):e003777. doi:10.1136/jitc-2021-003777.
7.
Munari E, Mariotti FR, Quatrini L, et al. PD-1/PD-L1 in Cancer: Pathophysiological, Diagnostic and Therapeutic Aspects. Int J Mol Sci. 2021;22(10):5123. doi:10.3390/ijms22105123.
8.
Ai L, Xu A, Xu J. Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond. Adv Exp Med Biol. 2020;1248:33–59. doi:10.1007/978-981-15-3266-5_3.
9.
Bagchi S, Yuan R, Engleman EG. Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance. Annu Rev Pathol. 2021;16:223–249. doi:10.1146/annurev-pathol-042020-042741.
10.
Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–1034. doi:10.1084/jem.192.7.1027.
11.
Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261–268. doi:10.1038/85330.
12.
Yi M, Zheng X, Niu M, Zhu S, Ge H, Wu K. Combination strategies with PD-1/PD-L1 blockade: current advanc92461099s00262es and future directions. Mol Cancer. 2022;21(1):28. doi:10.1186/s12943-021-01489-2.
13.
Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumour cells in the escape from host immune system and tumour immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99(19):12293–12297. doi:10.1073/pnas.192461099.
14.
Nakanishi J, Wada Y, Matsumoto K, Azuma M, Kikuchi K, Ueda S. Overexpression of B7-H1 (PD-L1) significantly associates with tumour grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother. 2007;56(8):1173–1182. doi:10.1007/s00262-006-0266-z.
15.
Ohigashi Y, Sho M, Yamada Y, et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res. 2005;11(8):2947–2953. doi:10.1158/1078-0432.CCR-04-1469.
16.
Hamanishi J, Mandai M, Iwasaki M, et al. Programmed cell death 1 ligand 1 and tumour-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci USA. 2007;104(9):3360–3365. doi:10.1073/pnas.0611533104.
17.
Favier A, Varinot J, Uzan C, et al. The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review. Cancers (Basel). 2022;14(15):3783. doi:10.3390/cancers14153783.
18.
Patnaik A, Weiss GJ, Rasco DW, et al. Safety, antitumour activity, and pharmacokinetics of dostarlimab, an anti-PD-1, in patients with advanced solid tumours: a dose-escalation phase 1 trial. Cancer Chemother Pharmacol. 2022;89(1):93–103. doi:10.1007/s00280-021-04358-3.
19.
Bregar A, Deshpande A, Grange C, et al. Characterization of immune regulatory molecules B7-H4 and PD-L1 in low and high grade endometrial tumours. Gynecol Oncol. 2017;145(3):446–452. doi:10.1016/j.ygyno.2017.03.006.
20.
Sloan EA, Ring KL, Willis BC, et al. PD-L1 Expression in Mismatch Repair-deficient Endometrial Carcinomas, Including Lynch Syndrome-associated and MLH1 Promoter Hypermethylated Tumours. Am J Surg Pathol. 2017;41(3):326–333. doi:10.1097/PAS.0000000000000783.
21.
Rowe M, Krishnan R, Mills A, et al. β-catenin and PD-L1 expression in mismatch repair deficient endometrial carcinomas. Int J Gynecol Cancer. 2020;30(7):993–999. doi:10.1136/ijgc-2020-001239.
22.
Fontenot VE, Tewari K. The current status of immunotherapy in the treatment of primary advanced and recurrent endometrial cancer. Curr Opin Obstet Gynecol. 2023;35(1):34–42. doi:10.1097/GCO.0000000000000839.
23.
Laken H, Kehry M, McNeeley P, et al. Identification and characterization of TSR-042, a novel anti-PD-1 therapeutic antibody. Eur J Cancer. 2016, 69(1):S102. doi.org/10.1016/S0959-8049(16)32902-1.
24.
Kumar S, Ghosh S, Sharma G, et al. Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models. MAbs. 2021;13(1):1954136. doi:10.1080/19420862.2021.1954136.
25.
Melhem M, Hanze E, Lu S, et al. Population pharmacokinetics and exposure-response of anti-programmed cell death protein-1 monoclonal antibody dostarlimab in advanced solid tumours. Br J Clin Pharmacol. 2022;88(9):4142–4154. doi:10.1111/bcp.15339.
26.
Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumours (GARNET). https://clinicaltrials.gov/ct2... (access 2023.08.11).
27.
Oaknin A, Ellard SL, Leath Iii, et al. Preliminary safety, efficacy, and PK/PD characterization from GARNET, a phase I clinical trial of the anti-PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced MSI-H endometrial cancer. Ann Oncol. 2018;29(1):viii334. doi.org/10.1093/annonc/mdy285.144.
28.
Oaknin A, Duska LR, Sullivan RJ, et al. Preliminary safety, efficacy, and pharmacokinetic/pharmacodynamic characterization from GARNET, a phase I/II clinical trial of the anti–PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced MSI-h and MSS endometrial cancer. Gynecol Oncol. 2019;154(1):17. doi.org/10.1016/j.ygyno.2019.04.044.
29.
Oaknin A, Tinker AV, Gilbert L, et al. Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. JAMA Oncol. 2020;6(11):1766–1772. doi:10.1001/jamaoncol.2020.4515.
30.
Berton D, Banerjee SN, Curigliano G, et al. Antitumour activity of dostarlimab in patients with mismatch repair-deficient/microsatellite instability–high tumours: A combined analysis of two cohorts in the GARNET study. J Clin Oncol. 2021;39(1):2564–2564. doi:10.1200/JCO.2021.39.15_suppl.2564.
31.
Oaknin A, Pothuri B, Gilbert L, et al. Dostarlimab in advanced/recurrent (AR) mismatch repair deficient/microsatellite instability–high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC): The GARNET study. J Clin Oncol. 2022;40(1):5509–5509. doi:10.1200/JCO.2022.40.16_suppl.5509.
32.
Howitt BE, Shukla SA, Sholl LM, et al. Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumour-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1. JAMA Oncol. 2015;1(9):1319–1323. doi:10.1001/jamaoncol.2015.2151.
33.
Zhao P, Li L, Jiang X, Li Q. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol. 2019;12(1):54. Published 2019 May 31. doi:10.1186/s13045-019-0738-1.
34.
Mercieca-Bebber R, King MT, Calvert MJ, et al. The importance of patient-reported outcomes in clinical trials and strategies for future optimization. Patient Relat Outcome Meas. 2018;9:353–367. doi:10.2147/PROM.S156279.
35.
Kristeleit R, Mathews C, Redondo A, et al. Patient-reported outcomes in the GARNET trial in patients with advanced or recurrent mismatchrepair-deficient/microsatellite instability-high endometrial cancer treated with dostarlimab. Int J Gynecol Cancer. 2022;32(10):1250–1257. doi:10.1136/ijgc-2022-003492.
36.
Kyriaki M, Eleni T, Efi P, Ourania K, Vassilios S, Lambros V. The EORTC core quality of life questionnaire (QLQ-C30, version 3.0) in terminally ill cancer patients under palliative care: validity and reliability in a Hellenic sample. Int J Cancer. 2001;94(1):135–139. doi:10.1002/ijc.1439.
37.
Dostarlimab in Patients With Recurrent or dMMR/MSI-H Endometrial Cancer (DORA). https://classic.clinicaltrials... NCT05728814 (access: 2023.08.11).
38.
Murai J, Huang SY, Das BB, et al. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012;72(21):5588–5599. doi:10.1158/0008-5472.CAN-12-2753.
39.
FDA approves niraparib for first-line maintenance of advanced ovarian cancer. https://www.fda.gov/ (access: 2023.08.11).
40.
Stewart RA, Pilié PG, Yap TA. Development of PARP and Immune-Checkpoint Inhibitor Combinations. Cancer Res. 2018;78(24):6717–6725. doi:10.1158/0008-5472.CAN-18-2652.
41.
Färkkilä A, Gulhan DC, Casado J, et al. Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer [published correction appears in Nat Commun. 2020 May 18;11(1):2543]. Nat Commun. 2020;11(1):1459. doi:10.1038/s41467-020-15315-8.
42.
Higuchi T, Flies DB, Marjon NA, et al. CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1-Deficient Ovarian Cancer. Cancer Immunol Res. 2015;3(11):1257–1268. doi:10.1158/2326- 6066.CIR-15-0044.
43.
Madariaga A, Garg S, Tchrakian N, et al. Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma. Nat Commun. 2023;14(1):1452. doi:10.1038/s41467-023-37084-w.
44.
Ray-Coquard IL, Leary A, Bigot F, et al. ROCSAN trial (GINECOEN203b/ENGOT-EN8): A multicentric randomized phase II/III evaluating dostarlimab in combination with niraparib versus niraparib alone compared to chemotherapy in the treatment of endometrial/ ovarian carcinosarcoma after at least one line of platinum based chemotherapy. J Clin Oncol. 2021;39(1):TPS5604-TPS5604. doi:10.1200/ JCO.2021.39.15_suppl.TPS5604.
45.
Toboni MD, Lomonosova E, Bruce SF, et al. Inhibition of AXL and VEGF-A Has Improved Therapeutic Efficacy in Uterine Serous Cancer. Cancers (Basel). 2021;13(23):5877. doi:10.3390/cancers13235877.
46.
Ho WJ, Zhu Q, Durham J, et al. Neoadjuvant Cabozantinib and Nivolumab Converts Locally Advanced HCC into Resectable Disease with Enhanced Antitumour Immunity. Nat Cancer. 2021;2(9):891–903. doi:10.1038/s43018-021-00234-4.
47.
Procopio G, Claps M, Pircher C, et al. A multicenter phase 2 single arm study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pre-treated with one immune-checkpoint inhibitor: The BREAKPOINT trial (Meet-Uro trial 03). Tumouri. 2023;109(1):129–137. doi:10.1177/03008916221138881.
48.
Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018;379(1):54–63. doi:10.1056/NEJMoa1717002.
49.
Cabozantinib and Dostarlimab in Recurrent Gynecologic Carcinosarcoma. https://classic.clinicaltrials... NCT05559879. (access: 2023.08.11).
50.
Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74(19):5458–5468. doi:10.1158/0008-5472. CAN-14-1258.
51.
Deng L, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumour immunity in mice. J Clin Invest. 2014;124(2):687–695. doi:10.1172/JCI67313.
52.
Sharabi AB, Lim M, DeWeese TL, et al. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 2015;16(13):e498-e509. doi:10.1016/S1470- 2045(15)00007-8.
53.
TSR-042 in Addition to Standard of Care Definitive Radiation for Inoperable Endometrial Cancer. https://classic.clinicaltrials... show/NCT03955978?term=TSR-042&cond=Neoplasms&draw=2&ra nk=4 (access: 2023.08.11).
54.
Radiation and Dostarlimab in People With Endometrial Cancer After They Receive Surgery. https://classic.clinicaltrials... /ct2/show/ NCT04774419?term=TSR-042&cond=Neoplasms&draw=2 (access: 2023.08.11).
55.
Dexter J, Lips E, DiSilvestro P. Adjuvant Therapy in Node-Positive Endometrial Cancer: A Focus on Chemotherapy. Curr Oncol Rep. 2022;24(12):1677–1683. doi:10.1007/s11912-022-01327-8.
56.
Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023;388(23):2145–2158. doi:10.1056/NEJMoa2216334.
57.
Phase I Trial Testing the Safety and Tolerability of Chemoradiation Followed by Chemotherapy + Dostarlimab for Stage IIIC, Node Positive, Endometrial Cancer. https://clinicaltrials.gov/ct2...? cond=dostarlimab+endometrial&draw=1&rank=3 (access: 2023.08.11).
58.
Endometrial Cancer Patients MMR Deficient Comparing Chemotherapy vs Dostarlimab in Firt Line (DOMENICA). https://classic.clinicaltrials. gov/ct2/show/NCT05201547?cond=dostarlimab+endometrial&draw= 1&rank=1 (access: 2023.08.11).
59.
Yap TA, Bessudo A, Hamilton E, et al. IOLite: phase 1b trial of doublet/ triplet combinations of dostarlimab with niraparib, carboplatinpaclitaxel, with or without bevacizumab in patients with advanced cancer. J Immunother Cancer. 2022;10(3):e003924. doi:10.1136/jitc-2021-003924.
60.
Falchook GS, Ribas A, Davar D, et al. Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and in combination with PD-1 inhibitors nivolumab or dostarlimab (AMBER). J Clin Oncol. 2022;40(1):2504– 2504. doi:10.1200/JCO.2022.40.16_suppl.2504.
61.
Laken H, Kehry M, McNeeley P, et al. Identification and characterization of TSR-042, a novel anti-PD-1 therapeutic antibody. Eur J Cancer. 2016;69(Suppl 1):S102.
62.
Fatima N, Tabbasum N, Mandava K. Dostarlimab, a boon or a healthcare burden – too early to acertain. Ann Med Surg (Lond). 2022;79:104050. doi:10.1016/j.amsu.2022.104050.
63.
Cercek A, Lumish M, Sinopoli J, et al. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022;386(25):2363–2376. doi:10.1056/NEJMoa2201445 64. Singh V, Sheikh A, Abourehab MAS, et al. Dostarlimab as a Miracle.
64.
Drug: Rising Hope against Cancer Treatment. Biosensors (Basel). 2022;12(8):617. doi:10.3390/bios12080617.
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