Monitoring for endometrial cancer recurrence currently relies on imaging techniques like computerized tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). These imaging tools are limited in their ability to detect early recurrences and expose patients to radiation and are costly. Circulating tumor DNA, or ctDNA can detected cancer in the blood long before it appears on a CT or MRI scan and has the potential to change how cancer is managed.3-6
The immune checkpoint inhibitors Keytruda, and Jemperli have recently become the new standard of care for treatment of advanced endometrial cancer.1,2 Side effects from these immune checkpoint inhibitors can be significant. Surveillance for recurrence with ctDNA testing can lead to early identification of recurrence, or complete response to therapy resulting in shorter immunotherapy treatment duration and avoidance of potential side-effects.
About ctDNA
Cancer is caused by genetic mutations, and these mutations can be detected by measuring circulating tumor DNA, or ctDNA, in the blood. Detection of ctDNA allows for personalized cancer surveillance based on an individual’s unique set of cancer mutations. Circulating tumor DNA is 150–200-base-pair fragments of DNA, which originate from cancer cells and are present in the bloodstream or other body fluids. ctDNA is different than cell-free DNA (cfDNA) which is ALL the DNA in the bloodstream including germline DNA and tumor DNA. ctDNA is the portion of cfDNA that is derived specifically from the cancer.
How is ctDNA used for the management of cancer?
Across all stages of surgically removed cancer, detection of ctDNA following surgery is a strong predictor of cancer recurrence. For example, measurement of ctDNA is performed routinely in early-stage colon cancer and may help clinicians and patients decide when to intensify therapy in certain situations, and conversely, the absence of ctDNA can provide an opportunity to minimize surveillance or avoid adjuvant treatment. In endometrial cancer the most immediate application of ctDNA monitoring is for the early detection of cancer recurrence and for Keytruda-Jemperli immunotherapy monitoring.
In an initial report evaluating ctDNA dynamics ctDNA was found to enable early detection of progressive disease and treatment response in patients with recurrent gynecological malignancies, receiving immunotherapy. Researchers utilized the personalized and tumor-informed multiplex PCR assay (Signatera™) for the detection of ctDNA in plasma samples in patients with recurrent gynecologic malignancies. ctDNA monitoring during immunotherapy treatment for patients with recurrent gynecologic malignancies allowed for accurate determination of therapeutic response and early prediction of disease progression.
Dr. John Strickler of Duke University recently conducted a webinar to explain ctDNA
About Signatera
Signatera is a custom-built ctDNA test for treatment monitoring and molecular residual disease assessment in patients diagnosed with cancer. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. Signatera is intended to detect and quantify cancer left in the body, at levels down to a single tumor molecule in a tube of blood.
The Centers for Medicare & Medicaid Services has determined that Signatera’s molecular residual disease (MRD) test designed to detect circulating tumor DNA, or ctDNA, has met coverage requirements for pan-cancer immunotherapy monitoring using its Signatera MRD test. Serial testing with Signatera is covered for Medicare patients being treated with immunotherapy, regardless of tumor type.
Over 200,000 patients per year are treated with immunotherapy yet only 20-30% of patients respond positively to immunotherapy. Therefore, many patients remain on treatment longer than necessary because ineffective treatment and disease progression is not detected early. Radiographic imaging is unable to differentiate between true disease progression and pseudo-progression. Results published in Nature Cancer demonstrate that personalized ctDNA monitoring with Signatera can identify individuals not responding to immunotherapy treatment with 100% positive predictive value, just 6 weeks into treatment.5,6
References
- A study to evaluate dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in participants with recurrent or primary advanced endometrial cancer (RUBY). ClinicalTrials.gov. Updated August 12, 2022. Accessed December 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03981796
- Makker V, Colombo, N, Casado Herráez A., et. al. A multicenter, open-label, randomized, phase 3 study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: Study 309/KEYNOTE-775. Annual Meeting of the Society of Gynecologic Oncology, 2021.
- https://www.nature.com/articles/s43018-020-0096-5
- Immunotherapy response monitoring using personalized circulating tumor DNA analysis in patients with relapsed gynecologic malignancies; Fernando Recio1, Brian Orr2, Kayla Castaneda3, Jose Salvador Saldivar3, Young Kwang Chae4, Hemant Sindhu5, Concepcion Diaz-Arrastia6, Kassondra Grzankowski7, Georges Azzi8, Carly Bess Scalise9, Ekaterina Kalashnikova9, Brittany Nicosia9, Tricia Beisch9, Charuta C. Palsuledesai9, Adam C. ElNaggar9, Minetta C. Liu9, Robert Holloway1
- QVIA™ Institute for Human Data Science Releases Global Oncology Trends 2019 Study: Record Number of Cancer Drugs Launched in 2018 across 17 Indications. IQVIA. https://www.iqvia.com/newsroom/2019/05/iqvia-institute-for-human-data-science-releases-global-oncology-trends-2019-study-record-number-of-c. Published 2019.
- Haslam A, et al. Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw Open. 2019; 2(5):e192535.
