Immunotherapy as a treatment strategy in advanced stage and recurrent
endometrial cancer: review of current phase III immunotherapy clinical
trials

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Abstract

The treatment of advanced stage, metastatic or recurrent endometrial cancer remains a clinically difficult scenario. Although combination carboplatin and paclitaxel is an effective standard-of-care regimen, alternate strategies have shown promise, particularly in biomarker select populations. In an effort to improve oncologic outcomes, investigators are exploring novel immunotherapy combinations. In this review, we discuss the clinical rationale and design of current phase III immuno-oncology clinical trials in patients with advanced stage or recurrent endometrial cancer.

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Most cited references 39

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Cancer Statistics, 2021

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.

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Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

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First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial.

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Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

Dung Le, Jennifer N. Durham, Kellie N Smith … (2017)

The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.

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Author and article information

Contributors

Ramez N. Eskander

Matthew A. Powell

Journal

Journal ID (nlm-ta): Ther Adv Med Oncol

Journal ID (iso-abbrev): Ther Adv Med Oncol

Journal ID (publisher-id): TAM

Journal ID (hwp): sptam

Title: Therapeutic Advances in Medical Oncology

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Print): 1758-8340

ISSN (Electronic): 1758-8359

Publication date (Electronic): 16 March 2021

Publication date Collection: 2021

Volume: 13

Electronic Location Identifier: 17588359211001199

Affiliations

[1-17588359211001199]Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Drive, La Jolla, CA 92093, USA

[2-17588359211001199]Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University School of Medicine, St. Louis, MO, USA

Author notes

[*] reskander@ 123456health.ucsd.edu

Article

Publisher ID: 10.1177_17588359211001199

DOI: 10.1177/17588359211001199

PMC ID: 7970168

PubMed ID: 33796152

SO-VID: 96e1efba-3c99-4206-99a1-95432a01585e

License:

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 2 February 2021

Date accepted : 15 February 2021

Custom metadata

cover-date January-December 2021

typesetter ts1

Keywords: antiangiogenic therapy,chemotherapy,combination therapy,endometrial cancer,immune checkpoint inhibition,immunotherapy,tumor mutational burden

Data availability:

Keywords: antiangiogenic therapy, chemotherapy, combination therapy, endometrial cancer, immune checkpoint inhibition, immunotherapy, tumor mutational burden

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Immunotherapy as a treatment strategy in advanced stage and recurrent endometrial cancer: review of current phase III immunotherapy clinical trials

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Cancer Immunotherapy

Most cited references 39

Cancer Statistics, 2021

Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

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