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Published in: Current Treatment Options in Oncology 10/2017

01-10-2017 | Gynecologic Cancers (LA Cantrell, Section Editor)

Immunotherapy in Gynecologic Cancers: Are We There Yet?

Authors: Janelle B. Pakish, MD, MS, Amir A. Jazaeri, MD

Published in: Current Treatment Options in Oncology | Issue 10/2017

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Opinion statement

Immune-targeted therapies have demonstrated durable responses in many tumor types with limited treatment options and poor overall prognosis. This has led to enthusiasm for expanding such therapies to other tumor types including gynecologic malignancies. The use of immunotherapy in gynecologic malignancies is in the early stages and is an active area of ongoing clinical research. Both cancer vaccines and immune checkpoint inhibitor therapy continue to be extensively studied in gynecologic malignancies. Immune checkpoint inhibitors, in particular, hold promising potential in specific subsets of endometrial cancer that express microsatellite instability. The key to successful treatment with immunotherapy involves identification of the subgroup of patients that will derive benefit. The number of ongoing trials in cervical, ovarian, and endometrial cancer will help to recognize these patients and make treatment more directed. Additionally, a number of studies are combining immunotherapy with standard treatment options and will help to determine combinations that will enhance responses to standard therapy. Overall, there is much enthusiasm for immunotherapy approaches in gynecologic malignancies. However, the emerging data shows that with the exception of microsatellite unstable tumors, the use of single-agent immune checkpoint inhibitors is associated with response rates of 10–15%. More effective and likely combinatorial approaches are needed and will be informed by the findings of ongoing trials.
Literature
1.
go back to reference Houot R, et al. T-cell-based immunotherapy: adoptive cell transfer and checkpoint inhibition. Cancer Immunol Res. 2015;3(10):1115–22.CrossRefPubMed Houot R, et al. T-cell-based immunotherapy: adoptive cell transfer and checkpoint inhibition. Cancer Immunol Res. 2015;3(10):1115–22.CrossRefPubMed
2.
go back to reference Lohmueller J, Finn OJ. Current modalities in cancer immunotherapy: immunomodulatory antibodies, CARs and vaccines. Pharmacol Ther. 2017; Lohmueller J, Finn OJ. Current modalities in cancer immunotherapy: immunomodulatory antibodies, CARs and vaccines. Pharmacol Ther. 2017;
4.
go back to reference •• Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60. Excellent review on immunologic cancer surveillance and immune-editingCrossRefPubMed •• Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60. Excellent review on immunologic cancer surveillance and immune-editingCrossRefPubMed
5.
go back to reference Vesely MD, et al. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71.CrossRefPubMed Vesely MD, et al. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71.CrossRefPubMed
6.
go back to reference Phan GQ, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2003;100(14):8372–7.CrossRefPubMedPubMedCentral Phan GQ, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2003;100(14):8372–7.CrossRefPubMedPubMedCentral
9.
go back to reference Larkin J, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.CrossRefPubMed Larkin J, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.CrossRefPubMed
10.
go back to reference • Hamanishi J, et al. Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2015;33(34):4015–22. First published report of a checkpoint inhibitor in ovarian cancerCrossRefPubMed • Hamanishi J, et al. Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2015;33(34):4015–22. First published report of a checkpoint inhibitor in ovarian cancerCrossRefPubMed
11.
go back to reference Disis ML, Patel MR, Pant S, Hamilton EP, Lockhart AC. Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: safety and clinical activity. J Clin Oncol. 2016;35(suppl; abstr 5533). Disis ML, Patel MR, Pant S, Hamilton EP, Lockhart AC. Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: safety and clinical activity. J Clin Oncol. 2016;35(suppl; abstr 5533).
12.
go back to reference Varga A, Piha-Paul SA, Ott PA, Mehnert JM, Berton-Rigaud D, Johnson EA, Cheng JD, Yuan S, Rubin EH, Mate DE. Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: interim results from a phase Ib study. J Clin Oncol. 2015;33(suppl; abstr 5510). Varga A, Piha-Paul SA, Ott PA, Mehnert JM, Berton-Rigaud D, Johnson EA, Cheng JD, Yuan S, Rubin EH, Mate DE. Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: interim results from a phase Ib study. J Clin Oncol. 2015;33(suppl; abstr 5510).
13.
go back to reference 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. 2017;35(19):2193–202.CrossRefPubMed 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. 2017;35(19):2193–202.CrossRefPubMed
14.
go back to reference Pujade-Lauraine E, Colombo N, Disis ML, Fujiwara K, Ledermann JA. Avelumab (MSB0010718C; anti-PD-L1) +/− pegylated liposomal doxorubicin vs pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory ovarian cancer: the phase III JAVELIN Ovarian 200 trial. J Clin Oncol. 2016;34(suppl; abstr TPS5600). Pujade-Lauraine E, Colombo N, Disis ML, Fujiwara K, Ledermann JA. Avelumab (MSB0010718C; anti-PD-L1) +/− pegylated liposomal doxorubicin vs pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory ovarian cancer: the phase III JAVELIN Ovarian 200 trial. J Clin Oncol. 2016;34(suppl; abstr TPS5600).
15.
go back to reference Wenham RM, Apte SM, Shahzad MM, Lee JK, Dorman D. Phase II trial of dose dense (weekly) paclitaxel with pembrolizumab (MK-3475) in platinum-resistant recurrent ovarian cancer. J Clin Oncol. 2016;34(suppl; abstr TPS5612). Wenham RM, Apte SM, Shahzad MM, Lee JK, Dorman D. Phase II trial of dose dense (weekly) paclitaxel with pembrolizumab (MK-3475) in platinum-resistant recurrent ovarian cancer. J Clin Oncol. 2016;34(suppl; abstr TPS5612).
16.
go back to reference Diefenbach CS, et al. Safety and immunogenicity study of NY-ESO-1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission. Clin Cancer Res. 2008;14(9):2740–8.CrossRefPubMed Diefenbach CS, et al. Safety and immunogenicity study of NY-ESO-1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission. Clin Cancer Res. 2008;14(9):2740–8.CrossRefPubMed
18.
go back to reference Sabbatini P, et al. Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin Cancer Res. 2012;18(23):6497–508.CrossRefPubMed Sabbatini P, et al. Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin Cancer Res. 2012;18(23):6497–508.CrossRefPubMed
19.
go back to reference Chu CS, et al. Phase I/II randomized trial of dendritic cell vaccination with or without cyclophosphamide for consolidation therapy of advanced ovarian cancer in first or second remission. Cancer Immunol Immunother. 2012;61(5):629–41.CrossRefPubMed Chu CS, et al. Phase I/II randomized trial of dendritic cell vaccination with or without cyclophosphamide for consolidation therapy of advanced ovarian cancer in first or second remission. Cancer Immunol Immunother. 2012;61(5):629–41.CrossRefPubMed
20.
go back to reference Baek S, et al. Therapeutic DC vaccination with IL-2 as a consolidation therapy for ovarian cancer patients: a phase I/II trial. Cell Mol Immunol. 2015;12(1):87–95.CrossRefPubMed Baek S, et al. Therapeutic DC vaccination with IL-2 as a consolidation therapy for ovarian cancer patients: a phase I/II trial. Cell Mol Immunol. 2015;12(1):87–95.CrossRefPubMed
22.
go back to reference Kawano K, et al. Feasibility study of personalized peptide vaccination for recurrent ovarian cancer patients. Immunopharmacol Immunotoxicol. 2014;36(3):224–36.CrossRefPubMed Kawano K, et al. Feasibility study of personalized peptide vaccination for recurrent ovarian cancer patients. Immunopharmacol Immunotoxicol. 2014;36(3):224–36.CrossRefPubMed
23.
go back to reference •• Dudley ME, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298(5594):850–4. Hallmark article of the efficacy of TIL adoptive cell therapy in melanomaCrossRefPubMedPubMedCentral •• Dudley ME, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298(5594):850–4. Hallmark article of the efficacy of TIL adoptive cell therapy in melanomaCrossRefPubMedPubMedCentral
24.
go back to reference Dudley ME, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23(10):2346–57.CrossRefPubMedPubMedCentral Dudley ME, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23(10):2346–57.CrossRefPubMedPubMedCentral
25.
go back to reference Dudley ME, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26(32):5233–9.CrossRefPubMedPubMedCentral Dudley ME, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26(32):5233–9.CrossRefPubMedPubMedCentral
26.
go back to reference Aoki Y, et al. Use of adoptive transfer of tumor-infiltrating lymphocytes alone or in combination with cisplatin-containing chemotherapy in patients with epithelial ovarian cancer. Cancer Res. 1991;51(7):1934–9.PubMed Aoki Y, et al. Use of adoptive transfer of tumor-infiltrating lymphocytes alone or in combination with cisplatin-containing chemotherapy in patients with epithelial ovarian cancer. Cancer Res. 1991;51(7):1934–9.PubMed
27.
go back to reference Freedman RS, et al. Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial. J Immunother Emphasis Tumor Immunol. 1994;16(3):198–210.CrossRefPubMed Freedman RS, et al. Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial. J Immunother Emphasis Tumor Immunol. 1994;16(3):198–210.CrossRefPubMed
28.
go back to reference Fujita K, et al. Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clin Cancer Res. 1995;1(5):501–7.PubMed Fujita K, et al. Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clin Cancer Res. 1995;1(5):501–7.PubMed
29.
go back to reference Ikarashi H, et al. Immunomodulation in patients with epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Cancer Res. 1994;54(1):190–6.PubMed Ikarashi H, et al. Immunomodulation in patients with epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Cancer Res. 1994;54(1):190–6.PubMed
30.
go back to reference Frenel JS, Le Tourneau C, O'Neil BH, Ott PA, Piha-Paul SA. Pembrozlizumab in patients with advanced cervical sqaumous cell cancer: preliminary results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2016;34(suppl; abstr 5515). Frenel JS, Le Tourneau C, O'Neil BH, Ott PA, Piha-Paul SA. Pembrozlizumab in patients with advanced cervical sqaumous cell cancer: preliminary results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2016;34(suppl; abstr 5515).
31.
go back to reference Schellens JHM, Marabelle A, Zeigenfuss S, Ding J, Pruitt SK, Chung HC. Pembrolizumab for previously treated advanced cervical squamous cell cancer: preliminary results from teh phase 2 KEYNOTE-158 study. J Clin Oncol. 2017;35(suppl; abstr 5514). Schellens JHM, Marabelle A, Zeigenfuss S, Ding J, Pruitt SK, Chung HC. Pembrolizumab for previously treated advanced cervical squamous cell cancer: preliminary results from teh phase 2 KEYNOTE-158 study. J Clin Oncol. 2017;35(suppl; abstr 5514).
32.
go back to reference Delord JP, Hollebecque A, De Boer JP, De Greve J, Machiels JPH, Leidner RS, Ferris RL, Roa S, Soumaoro I, Cao ZA, Kang H, Topalian SL. An open-label, multicohort, phase I/II study to evaluate nivolumab in patients with virus-associated tumors (CheckMate 358): efficacy and safety in recurren or metastatic (R/M) nasopharyngeal carcinoma (NPC). J Clin Oncol. 2017;35(suppl; abstr 6025). Delord JP, Hollebecque A, De Boer JP, De Greve J, Machiels JPH, Leidner RS, Ferris RL, Roa S, Soumaoro I, Cao ZA, Kang H, Topalian SL. An open-label, multicohort, phase I/II study to evaluate nivolumab in patients with virus-associated tumors (CheckMate 358): efficacy and safety in recurren or metastatic (R/M) nasopharyngeal carcinoma (NPC). J Clin Oncol. 2017;35(suppl; abstr 6025).
33.
go back to reference Paraghamian SE, Longoria TC, Eskander RN. Metastatic small cell neuroendocrine carcinoma of the cervix treated with the PD-1 inhibitor, nivolumab: a case report. Gynecol Oncol Res Pract. 2017;4:3.CrossRefPubMedPubMedCentral Paraghamian SE, Longoria TC, Eskander RN. Metastatic small cell neuroendocrine carcinoma of the cervix treated with the PD-1 inhibitor, nivolumab: a case report. Gynecol Oncol Res Pract. 2017;4:3.CrossRefPubMedPubMedCentral
34.
go back to reference Basu P, Mehta AO, Jain MM, Gupta S, Rajnish VN, Kumar V, Premkumar S, Neve R, John S, Petit RG. ADXS11-001 immunotherapy targeting HPV-E7: Final results from a phase 2 study in Indian women with recurrent cervical cancer. J Clin Oncol. 2014;32:5s(suppl; abstr 5610). Basu P, Mehta AO, Jain MM, Gupta S, Rajnish VN, Kumar V, Premkumar S, Neve R, John S, Petit RG. ADXS11-001 immunotherapy targeting HPV-E7: Final results from a phase 2 study in Indian women with recurrent cervical cancer. J Clin Oncol. 2014;32:5s(suppl; abstr 5610).
35.
go back to reference Huh W, Brady WE, Dizon D, Powel MA, Leath CA, Landrum LM, Tanner E, Higgins R, Ueda S, McHale M. A prospective phase 2 trial (GOG-0265) of the Listeria-based HPV immunotherapy axalimogene filolisback (AXAL) in second- and third-line metastatic cervical cancer: an NRG Oncology Group trial. SGO Annual Meeting, 2017. Huh W, Brady WE, Dizon D, Powel MA, Leath CA, Landrum LM, Tanner E, Higgins R, Ueda S, McHale M. A prospective phase 2 trial (GOG-0265) of the Listeria-based HPV immunotherapy axalimogene filolisback (AXAL) in second- and third-line metastatic cervical cancer: an NRG Oncology Group trial. SGO Annual Meeting, 2017.
36.
go back to reference Monk BJ, et al. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009;27(7):1069–74.CrossRefPubMedPubMedCentral Monk BJ, et al. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009;27(7):1069–74.CrossRefPubMedPubMedCentral
37.
go back to reference Dellinger TH, Monk BJ. Systemic therapy for recurrent endometrial cancer: a review of North American trials. Expert Rev Anticancer Ther. 2009;9(7):905–16.CrossRefPubMed Dellinger TH, Monk BJ. Systemic therapy for recurrent endometrial cancer: a review of North American trials. Expert Rev Anticancer Ther. 2009;9(7):905–16.CrossRefPubMed
38.
go back to reference Dizon DS. Treatment options for advanced endometrial carcinoma. Gynecol Oncol. 2010;117(2):373–81.CrossRefPubMed Dizon DS. Treatment options for advanced endometrial carcinoma. Gynecol Oncol. 2010;117(2):373–81.CrossRefPubMed
39.
go back to reference • Alexandrov LB, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21. Frequently cited reference on tumor classification by number of somatic mutationCrossRefPubMedPubMedCentral • Alexandrov LB, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21. Frequently cited reference on tumor classification by number of somatic mutationCrossRefPubMedPubMedCentral
40.
go back to reference Howitt BE, et al. Association of polymerase e–mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of pd-1 and pd-l1. JAMA Oncology. 2015; Howitt BE, et al. Association of polymerase e–mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of pd-1 and pd-l1. JAMA Oncology. 2015;
42.
go back to reference Ott PA, et al. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol. 2017;35(22):2535–41.CrossRefPubMed Ott PA, et al. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol. 2017;35(22):2535–41.CrossRefPubMed
Metadata
Title
Immunotherapy in Gynecologic Cancers: Are We There Yet?
Authors
Janelle B. Pakish, MD, MS
Amir A. Jazaeri, MD
Publication date
01-10-2017
Publisher
Springer US
Published in
Current Treatment Options in Oncology / Issue 10/2017
Print ISSN: 1527-2729
Electronic ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-017-0504-y

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