An Overview of Immune Checkpoint Inhibitors in Gynecologic Cancers

Castellano, T.; Moore, Kathleen N.; Holman, Laura L.

doi:10.1016/j.clinthera.2018.01.005

Cited by 19 publications

(18 citation statements)

References 58 publications

(125 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pembrolizumab is now approved for several other cancer types including non-small cell squamous cell carcinoma, recurrent head and neck squamous cell cancer, and solid cancers with high microsatellite instability (MSI-H) or mismatch repair (MMR) gene defects, including endometrial cancer [22,23]. There are now several other FDA-approved antibodies targeting the PD-1 axis [12,24], many of which are in single and combination therapy clinical trials for ovarian cancer, endometrial cancer, and other malignancies [25,26].…”

Section: Immune Checkpoint Junctions In Cancer Immunotherapymentioning

confidence: 99%

“…Combination therapy has the potential to afford additive or synergistic benefits, as compared to single agent treatment, as well as to overcome resistance mechanisms that are observed with ICI monotherapy administration, due to the upregulation of alternative immune checkpoint molecules or to emerging resistance caused by the presence of cells such as myeloid-derived suppressor cells (MDSCs) [61][62][63][64][65]. Currently, several clinical trials are ongoing with ICI treatment in EC patients, which are used in combination with cytotoxic chemotherapy, other ICI, vaccines and other immunotherapies, or targeted therapies [25,26,29,32,66].…”

Section: Immune Checkpoint Blockade Therapy In Endometrial Cancermentioning

confidence: 99%

“…Based on these and other studies, ICI treatment is generally regarded as very promising as an alternative therapy option for advanced/recurrent EC. A more detailed list of ongoing EC clinical trials using monotherapy and combination therapy regimens are summarized elsewhere [25,26,29,32].…”

Section: Immune Checkpoint Blockade Therapy In Endometrial Cancermentioning

confidence: 99%

See 2 more Smart Citations

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Drakes

Czerlanis

Stiff

2020

Cancers

View full text Add to dashboard Cite

This review provides an update on the current use of immune checkpoint inhibitors (ICI) in female gynecologic cancers, and it addresses the potential of these agents to provide therapy options for disease management and long-term remission in advanced disease patients, where surgery, chemotherapy, and/or radiation fail to meet this goal. The topic of immune checkpoint inhibitors (ICI) blocking cytotoxic T lymphocyte associated protein-4 (CTLA-4) and the programmed death-1 (PD-1) axis has come to the forefront of translational medicine over the last decade for several malignancies. The text will focus primarily on a discussion of ovarian cancer, which is the most frequent cause of death of gynecologic cancers; endometrial cancer, which is the most often diagnosed gynecologic cancer; and cervical cancer, which is the third most common female gynecologic malignancy, all of which unfavorably alter the lives of many women. We will address the critical factors that regulate the outcome of these cancer types to ICI therapy, the ongoing clinical trials in this area, as well as the adverse immune responses that impact the outcome of patients given ICI regimens.

show abstract

Section: Immune Checkpoint Junctions In Cancer Immunotherapymentioning

confidence: 99%

Section: Immune Checkpoint Blockade Therapy In Endometrial Cancermentioning

confidence: 99%

See 1 more Smart Citation

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Drakes

Czerlanis

Stiff

2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Linda Duska and Leigh Cantrell, have invited a collection of articles entitled Targeted Therapies in Gynecologic Malignancies. [5][6][7][8] These articles shed light on the status of targeted therapies for gynecologic tumors, including immunotherapies, angiogenesis inhibitors, and poly (ADP-ribose) polymerase (PARP) inhibitors. In addition, certain untoward complications from their use are discussed.…”

mentioning

confidence: 99%

Reflections on Oncotherapies

Shader¹

2018

Clinical Therapeutics

View full text Add to dashboard Cite

Reflections on Oncotherapies When I lectured on cancer chemotherapy, I would often start out by saying, "There are many ways to skin a cat." I would explain that by cat I meant a CAncerous Tumor. I would then engage the students by asking them to suggest ways to treat cancers. Before I go into their answers, I want to comment on how I learned this phrase. Growing up in Florida, we used to catch a lot of catfish and skin them in preparation for cooking. When I was preparing for this Note, I decided to look up the origins of "ways to skin a cat." I was surprised to learn that the phrase actually stems from debates in England in 1932 about whether cats should be skinned when still alive or only once dead! 1 I would start the list of answers by giving students the most common answer, surgical removal, and then relate what one of my surgical teachers used to say, "When in doubt, cut it out." The students' additional answers usually ended up (in no specific order) as follows: (1) radiation to destroy the mass or to reduce its size (we called that "zap it"), (2) chemotherapy to halt tumor growth at different stages of cellular division and maturation, (3) cutting off a tumor's blood supply, and (4) harnessing and enhancing the body's own antitumor defenses. We would also discuss issues such as solid versus hematologic cancers and primary versus metastatic lesions. Point 4 above is where much excitement and attention is currently focused. There is a new language and associated sets of acronyms that clinicians have to learn. The public is also exposed to this new vocabulary through television and print advertising. I saw a television ad today for the injectable monoclonal antibody, pembrolizumab *. It is the only immunotherapy approved for solid tumors that have increased levels of microsatellite instability, which is a function of impaired DNA mismatch repair. These tumor cells have numerous DNA repeats that make them vulnerable to mutations. Tumors of the endometrium, distal colon, and gastrointestinal tract are particularly prone to microsatellite instability. An Internet ad I saw focused on the use of pembrolizumab for some forms of melanoma as well as for metastatic non-small-cell lung cancer. Keytruda's product information states that when used for the latter, the tumor material should test "… positive for 'PD-L1' and … not have an abnormal 'EGFR' or 'ALK' gene." 2 Solid tumors with high levels of microsatellite instability are particularly sensitive to PD-1/PD-L1 immunotherapy. Acronyms such as PD-1 must be confusing to the average patient or consumer. For those readers unfamiliar with these terms, let's discuss the PD-1/PD-L1 acronym. PD stands for programmed cell death. Circulating activated T cells (lymphocytes) seek out unhealthy and cancerous cells as part of the body's immune system. PD-1 is a surface receptor on these T cells that keeps them from destroying cells in the body. PD-L1 is a ligand on the surface of cancerous cells and on some normal cells; it is often present in large amounts on some cancer cell...

show abstract

“…7 In their review devoted to the checkpoint inhibitors, Castellano and colleagues provide an overview of these agents and their study in gynecologic malignancies. 8 Although patients with microsatellite unstable tumors benefit from checkpoint inhibitors, in stable tumors, the use of single-agent immune checkpoint inhibitors is associated with response rates of 5% to 15%. 9,10 In this setting, there is interest in combining the checkpoint inhibitors with cytotoxic chemotherapy and with other targeted agents.…”

mentioning

confidence: 99%

Targeted Therapies and Immunotherapy for Gynecologic Malignancies: Living Longer, Living Better With Noncytotoxic Options in Recurrent Disease

Cantrell

Duska

2018

Clinical Therapeutics

View full text Add to dashboard Cite

Recurrent gynecologic malignancies are difficult to treat. Ovarian cancer is the most lethal of the gynecologic malignancies and once recurrent is incurable. However, today women with recurrent ovarian cancer are living longer and additionally enjoying an acceptable quality of life. 1 Women with cervical and endometrial cancer also have increasing treatment options in the recurrent disease setting. 2 The observed improved disease outcome is due, in part, to the development of multiple new noncytotoxic treatments. Angiogenesis inhibitors, particularly bevacizumab, were the first game-changers in gynecologic cancers. The relatively recent approval of poly (ADP-ribose) polymerase (PARP) inhibitors for ovarian cancer and the enthusiasm regarding the use of immune checkpoint inhibitors for all gynecologic malignancies continue to broaden the landscape of options for women with recurrent disease. Studies are ongoing with these new drugs as single agents and in combination with cytotoxic chemotherapy and with each other. The concept of this Specialty Update was to provide a broad overview of the newer noncytotoxic options in the treatment of gynecologic malignancies. There are multiple examples of new drug approvals in gynecologic malignancy in the past decade. In 2014, the US Food and Drug Administration (FDA) approved bevacizumab in combination with chemotherapy for use in both recurrent platinum-resistant ovarian cancer and recurrent cervical cancer. That year, olaparib, the first PARP inhibitor, was also approved. Subsequent approvals of two other PARP inhibitors have radically changed the approach to recurrent ovarian cancer. Recently, niraparib and olaparib were approved for maintenance therapy following second-line platinum-based therapy in all ovarian cancer patients and has changed the standard of care in this setting. Importantly, this therapy has improved progression-free survival while maintaining quality of life. Most recently, the PD-1 inhibitors pembrolizumab and nivolumab have been approved for microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed after previous treatment, an approval that will provide a new option for women with MSI-H recurrent endometrial cancer (~20% will be MSI-H) and other MSI-H gynecologic malignancies. The checkpoint inhibitors, six of which have been FDA approved for other indications, are the newest addition to the treatment of gynecologic cancers. Several studies suggest potential activity as single agents in recurrent ovarian cancer, 3-5 and there is significant interest in their role in MSI-H endometrial cancers. At present, the limitation remains identifying the patients who will benefit from a specific immunotherapy. Although initially all of these treatments have been used as single agents and in the recurrent disease setting, investigation has expanded to combination therapy and even to the upfront setting in ovarian cancer. For example, bevacizumab has been studied in ovarian cancer in the front-line setting (GOG 218 and I...

show abstract

An Overview of Immune Checkpoint Inhibitors in Gynecologic Cancers

Cited by 19 publications

References 58 publications

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Reflections on Oncotherapies

Targeted Therapies and Immunotherapy for Gynecologic Malignancies: Living Longer, Living Better With Noncytotoxic Options in Recurrent Disease

Contact Info

Product

Resources

About