DUO-E is the first global phase III study of Immunotherapy Plus
PARP inhibition to demonstrate clinical utility in this setting
The Phase III DUO-E study has achieved very positive resultsResumé(durvalumab) in combination with platinum-based chemotherapy followed by eitherResuméPlusLynparz(be improved) LubResuméas maintenance therapy alone, both showed a statistically significant and clinically significant improvement in progression-free survival (PFS) compared with standard chemotherapy in patients with newly diagnosed advanced or recurrent endometrial cancer. A greater clinical benefit was observed with combinationResuméILynparzas maintenance therapy.
Overall survival (OS) data were immature at the time of this analysis, but a favorable trend was observed for both regimens.
Endometrial cancer is the sixth most common cancer in women worldwide. In 2020, over 417,000 patients were diagnosed and over 97,000 deaths were recorded.1By 2040, the number of diagnoses is expected to increase by almost 40%.2The current standard of care for advanced endometrial cancer is chemotherapy.3,4However, long-term outcomes in first-line endometrial cancer remain poor and new treatment options are needed.5,6
Shannon N. Westin, professor of gynecologic oncology and reproductive medicine at the University of Texas MD Anderson Cancer Center and principal investigator of the DUO-E study, said, "These exciting data show that durvalumab immunotherapy can reduce disease progression in endometrial patients and significantly delay cancer." Adding the PARP inhibitor olaparib may further increase the benefits. These combinations may offer physicians a new treatment approach to improve patient outcomes."
Susan Galbraith, vice president of oncology research and development at AstraZeneca, said: "These DUO-E data show for the first time that the combination of immunotherapy and a PARP inhibitor can provide significant clinical improvement for endometrial cancer patients." cancer treatment, and we hope to innovate in this wayResuméILynparzcombination to give it to patients with endometrial cancer as soon as possible."
Safety and tolerance profileResuméplus chemotherapy and odResuméin combination withLynparzwere generally consistent with the results of previous clinical trials and the known profiles of the individual drugs.7,8
This data will be presented at an upcoming medical meeting and we look forward to discussing it with the health authorities.
Endometrial cancer is a highly heterogeneous disease that originates from the endometrium and is most common in postmenopausal women. The average age at diagnosis is over 60 years.9-11Both morbidity and mortality from endometrial cancer are expected to increase from 417,400 cases and 97,400 deaths in 2020 to 608,130 cases and 157,813 deaths in 2040.1,2
Most endometrial cancer patients are diagnosed early in the disease, when the cancer is confined to the uterus. They are usually treated with surgery and/or radiation therapy, and the 5-year survival rate is high (around 95%). However, patients with advanced disease (stage III-IV) are usually treated with chemotherapy and have a much poorer prognosis, with 5-year survival rates falling to around 20-30%.4,5,11,12,13
For patients whose disease is progressive or recurrent, treatment options are limited as the cancer is not expected to respond to hormone therapy and is treated with chemotherapy.5,6
Study DUO-E (GOG 3041/ENGOT-EN10) is a three-arm, randomized, double-blind, placebo-controlled, multicenter, phase III, first-line therapy studyResuméin combination with platinum-based chemotherapy (carboplatin and paclitaxel) followed byResumézLynparzLubResuméas maintenance therapy compared to platinum-based chemotherapy alone in the treatment of patients with newly diagnosed advanced or recurrent endometrial cancer.
In the DUO-E study, 699 patients with newly diagnosed or recurrent stage III or IV endometrial cancer (excluding sarcoma) were randomized to 1120 mgResuméor placebo administered every three weeks in combination with standard platinum-based chemotherapy. At the end of chemotherapy, patients received either 1,500 mgResuméor placebo every four weeks as maintenance therapy or in combination with 300 mg BID (2 x 150 mg tablets twice daily).Lynparzor placebo until disease progression for 24 months.
The dual primary endpoint was PFS, and mismatch repair status (MMR) was one of the stratification factors. Key secondary endpoints included OS, objective response rate (ORR), duration of response (DoR), and safety and tolerability. The study was conducted at 253 research centers in 22 countries, including the United States, Europe, South America and Asia.
More information about the study can be found on the websiteClinicalTrials.gov.
Resumé(Durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction between PD-L1 and the PD-1 and CD80 proteins, counteracting the tumor's immune defense tactics and reversing the suppression of the immune response.
Resuméis the only approved immunotherapy and the world standard for the treatment of unresectable stage III non-small cell lung cancer (NSCLC) with the intention of curing patients who have not progressed after radiochemotherapy, based on the phase III PACIFIC trial.Resuméit is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of advanced small cell lung cancer (SCLC) based on the CASPIAN phase III trial. other than thatResuméis allowed in combination with a short courseImjudo(tremelimumab) and chemotherapy for the treatment of metastatic NSCLC in the USA, EU and Japan, based on the phase III POSEIDON trial.
In addition to indications for lung cancer,Resuméis also permitted in connection withChemotherapy for locally advanced or metastatic cholangiocarcinoma in the US, EU, Japan and several other countries; in combination withImjudoin unresectable hepatocellular carcinoma in the US, EU and Japan; and in several countries in previously treated patients with advanced bladder cancer.
More than 150,000 patients have been treated with it since it was first approved in May 2017Resumé. As part of a comprehensive development programResuméit is being tested as a single therapy and in combination with other cancer treatments in patients with SCLC, NSCLC, bladder cancer, many gastrointestinal cancers, and other solid tumors.
Lynparz(Olaparib) is the first in class PARP inhibitor and the first targeted DNA damage response (DDR) blocker in cells/cancers lacking homologous recombination genes (HRR), eg BRCA1 and/or BRCA2 mutations, or whose deficiency is caused by other active substances (e.g. new hormone active substances [NHA]).
inhibition of PARP withLynparzleading to the capture of PARP associated with DNA single-strand breaks, stalling of replication forks, their collapse and formation of DNA double-strand breaks, and cancer cell death.
Lynparzis currently approved in many countries for use in many types of cancer, including maintenance treatment of platinum-sensitive recurrent ovarian cancer, and both as monotherapy and in combination with bevacizumab for first-line maintenance treatment of BRCA mutant (BRCAm) and homologous recombination repair deficiency (HRD)-positive advanced ovarian cancer; in germline BRCA mutation (gBRCAm), HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); gBRCAm, HER2-negative high-risk early breast cancer (in Japan, this includes all BRCAm-HER2-negative high-risk early breast cancer); for metastatic pancreatic cancer gBRCam; in combination with abiraterone for the treatment of metastatic castration-resistant prostate cancer when chemotherapy is not clinically indicated (EU only) and as monotherapy for HRR-mutated castration-resistant prostate cancer in patients who have progressed on previous NHA therapy (BRCam). only in the EU and Japan). In China,Lynparzis approved for the treatment of BRCA mutation-resistant castration-resistant prostate cancer and as first-line maintenance treatment with bevacizumab in HRD-positive advanced ovarian cancer.
Lynparz,The drug was jointly developed and marketed by AstraZeneca and MSD and has been used to treat over 75,000 patients worldwide. Companies evolveLynparzindependently in combination with the appropriate drugs PD-L1 and PD-1.Lynparzis the basis of AstraZeneca's industry-leading portfolio of potential new drugs targeting DDR mechanisms in cancer cells.
AstraZeneca and oncology
AstraZeneca is leading the revolution in oncology to provide a cure for all forms of cancer, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The company focuses on some of the most difficult forms of cancer. Through continuous innovation, AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to drive change in medical practice and transform the patient experience.
By leveraging the power of six scientific platforms - immuno-oncology, cancer factors and resistance, DNA damage response, antibody drug conjugates, epigenetics and cell therapies - and supporting the development of personalized combinations, AstraZeneca has a vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
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1. International World Cancer Research Fund. Endometrial cancer statistics. Available athttps://www.wcrf.org/cancer-trends/endometrial-cancer-statistics/. Access in May 2023.
2. IARC. WHO. the body of the uterus. 2020 to 2040 Estimates, Women, Age [0-85+] World. Available at:https://gco.iarc.fr/tomorrow/en/dataviz/trendsAccess in May 2023.
3. Carlson R. Carboplatin-paclitaxel therapy in advanced endometrial cancer shows promise.times with oncology. 2003;25(22):36.
4. Ferris JS et al. Serous carcinoma of the uterus: important advances and new approaches to treatment.International Journal of Gynecological Pathology. 2021;31(8):1165-1174.
5. Matrai CE et al. Molecular assessment of low-grade, recurrent and non-recurrent endometrial cancer.International Journal of Gynecological Pathology. 2022;41(3):207-219.
6. Soumerai T et al. Clinical utility of prospective molecular characterization in advanced endometrial cancer.Clin Cancer Res.2018 1. Dez.;24(23):5939-5947.
7.FDA. Prescriptive Highlights –Lynparz. Available athttps://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208558s014lbl.pdf. Access in May 2023.
8.FDA. Prescriptive Highlights –Resumé. Available athttps://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761069s018lbl.pdf. Access in May 2023.
9. Dorek T,I in. Genetic susceptibility to endometrial cancer: risk factors and clinical management.forms of cancer(Basel). 2020 sep;12(9):2407.
10. American Cancer Society. What is endometrial cancer? Available athttps://www.cancer.org/cancer/endometrial-cancer/about/what-is-endometrial-cancer.html.Access in May 2023.
11. Oakin A,I in.ESMO guidelines. Endometrial cancer: ESMO clinical guidelines for diagnosis, treatment and follow-up.Anna Onkol.2022 sep;33(9):860-877.
12. Wright JD,I in.Modern treatment of endometrial cancer.Lanzette. 7. april 2012;379(9823):1352-60.
13. Munk BJ,I in.Actual outcomes in patients with advanced endometrial cancer: a retrospective electronic medical record cohort study in the United States.Gynecologic Oncology. 2022;164(2):325-332.
IMFINZI is an immunotherapy that is approved to treat certain cancers.What is the most likely treatment plan for recurrent endometrial cancer? ›
Locally advanced or recurrent endometrial cancer can be treated via surgery, radiation therapy, hormonal therapy, or chemotherapy.What is the new drug for endometrial cancer? ›
Over the last 2 years, pembrolizumab and dostarlimab were approved by the Food and Drug Administration (FDA) to treat women with advanced or recurrent endometrial cancer whose disease had worsened after initial, or first-line, treatment with chemotherapy.Is there immunotherapy for endometrial cancer? ›
Immunotherapy is an emerging area of research and treatment for endometrial cancer. Immunotherapy is class of treatments that take advantage of a person's own immune system to help kill cancer cells. There are currently two FDA-approved immunotherapies for the treatment of uterine cancer.Is immunotherapy as harsh as chemo? ›
The side effects of immunotherapy generally become less severe after the first treatment. For chemotherapy, most side effects subside once treatment is completed. “One advantage of chemo is that the side effects appear when the treatment starts, but once you stop the chemo, most of those side effects go away.Is immunotherapy as hard on you as chemo? ›
Immunotherapy, in general, is less toxic than chemotherapy for patients with cancer.Which type of endometrial cancer has best prognosis? ›
Women with early stage (FIGO I/II) endometrial cancer have a favourable prognosis compared to those with advanced disease (FIGO III/IV). The 5-year survival rate is >90% in early stage disease and <20% in late stage disease (17, 21).What is the best prognosis for endometrial cancer? ›
Outlook / Prognosis
The five-year survival rate for endometrial cancer is 81%. That means 81% of people diagnosed with the disease are alive five years later. The rate is even higher when cancer hasn't spread outside your uterus. Then, the survival rate reaches as high as 95%.
Surgery is the main treatment for endometrial cancer. Usually surgery for endometrial cancer includes: Total hysterectomy (surgical removal of the uterus) Bilateral salpingo-oophorectomy (removal of both ovaries and Fallopian tubes)Can advanced endometrial cancer be cured? ›
Due to early detection and treatment, the prognosis of endometrial cancer is excellent for most patients. The chances of a cure depends largely on the type of endometrial cancer and the stage at which endometrial cancer is diagnosed.
90 out of every 100 (90%) survive their cancer for 1 year or more after they are diagnosed. around 75 out of every 100 (around 75%) will survive their cancer for 5 years or more. more than 70 out of every 100 (more than 70%) will survive their cancer for 10 years or more after diagnosis.How long can immunotherapy extend your life? ›
A study conducted by UCLA researchers involving patients with non-small cell lung cancer (NSCLC) found that the immunotherapy drug pembrolizumab increased the average 5-year survival rate of these patients from 5.5% to 15%.Can immunotherapy cure stage 4 cancer? ›
Can immunotherapy cure stage 4 cancer? While immunotherapy doesn't cure stage 4 cancer, it can improve the quality and longevity of your life.What is the success rate of chemotherapy for endometrial cancer? ›
75% for women with stage IB. 69% for women with stage II. 58% for women with stage IIIA.What stage of endometrial cancer requires chemo? ›
Chemotherapy for endometrial cancer is generally reserved for stages III and IV (as needed) unless certain pathologies of uterine cancer are diagnosed, including uterine carcinosarcomas, clear cell cancers, or serous cancers.Who is not a good candidate for immunotherapy? ›
If you have an autoimmune disorder, you may be unable to tolerate immunotherapy even if you would otherwise qualify for treatment. With an autoimmune disease, such as lupus, rheumatoid arthritis, Crohn's disease or ulcerative colitis, your immune system mistakenly attacks healthy cells.What not to eat during immunotherapy? ›
Try avoiding foods that could cause more pain like acidic foods (citrus, tomatoes, vinegar), or alcoholic or carbonated drinks. Cold or frozen foods like popsicles can be soothing, and it may help to use a straw or suck on ice. For weight loss: Maintaining weight is important during cancer treatment.Why immunotherapy is not recommended? ›
Immunotherapy may cause lowered blood counts, which may lead to bleeding, anemia, and other problems. Lungs. Immune checkpoint inhibitors may cause pneumonitis, which is inflammation of the lungs that can cause a cough or trouble breathing. Pneumonitis is uncommon but may be serious.Why is immunotherapy a last resort? ›
Over time, immunotherapy may stop having an effect on your cancer cells. This means that even if it works at first, your tumor could start to grow again.How sick do you get with immunotherapy? ›
Flu-like symptoms: Some immunotherapy drugs can make you feel like you have the flu. Along with a fever, you could have a headache, nausea, muscle or joint aches, chills, weakness, and dizziness. Some people also get a runny nose, dry cough, or diarrhea. There's no single way to treat all these symptoms.
Certain cancers, including pancreatic cancer, prostate cancer and glioblastoma, have been especially resistant to this approach.What is the most aggressive type of endometrial cancer? ›
Uterine sarcoma. Uterine sarcoma develops in the muscle wall of the uterus, also called the myometrium. Fewer than 10 percent of uterine cancer cases are uterine sarcoma. Uterine sarcomas are often more aggressive than other types of uterine cancer.Which endometrial carcinoma has worse prognosis? ›
High-grade serous and clear cell carcinomas overall have been associated with significantly poorer 5-year survival rates than high-grade endometrioid carcinomas.Where does endometrial cancer spread first? ›
Endometrial cancer typically grows from the endometrium (the inside of the uterus) into the surrounding muscle layer (the myometrium) towards the outer lining of the uterus. It can also grow into the adjacent fallopian tubes, which are attached to the uterus and from here to the ovaries.Can you beat Stage 4 endometrial cancer? ›
Survival rates may reach as high as 90 percent in certain instances. As the stage of cancer progresses, the likelihood of survival decreases. Women who are diagnosed with stage IV (4) endometrial cancer have a five-year survival rate of around 15 percent.What is the rare aggressive endometrial cancer? ›
Uterine papillary serous carcinoma (UPSC) is a rare form of endometrial cancer that comprises about 5% of all cases. It spreads faster and is more likely to recur following treatment than all other types of cancer, even when detected early. Women who are African American and postmenopausal are at higher risk for UPSC.Is endometrial cancer an aggressive cancer? ›
The endometrium is part of the uterus, so endometrial cancer is often referred to as uterine cancer. Uterine sarcomas, which develop in the muscle tissue of the uterus (the myometrium). This type is rare, but is also the most aggressive form of uterine cancer.What is the best hospital for endometrial cancer? ›
Mayo Clinic doctors have extensive experience treating many cases of endometrial cancer, as well as the other, rarer types of cancer that can affect the uterus, such as uterine sarcoma. Nationally recognized expertise.Is endometrial cancer 100% curable? ›
Overview. While a diagnosis of uterine cancer can be scary, it is important to know that its most common form—endometrial cancer—is curable, especially if it is caught at an early stage. Uterine cancer is a blanket term for cancers that can develop inside a woman's uterus.Can you beat stage 3 endometrial cancer? ›
Treatment of stage III uterine cancer with surgery followed by adjuvant brachytherapy and/ or external beam radiation therapy has been reported to cure approximately 50% of patients.
Imfinzi is an immunotherapy treatment for these types of cancer. It helps your immune system attack the cancer. Imfinzi belongs to a class of drugs called PD-L1 inhibitors.What is the key difference between immunotherapy and chemotherapy? ›
While chemotherapy works to kill cancer cells, immunotherapy aims to boost the body's own immune system to fight cancer.What type of treatment is IMFINZI? ›
IMFINZI IS AN IMMUNOTHERAPY—NOT CHEMOTHERAPY
IMFINZI is a type of cancer treatment that works with the immune system to find and attack certain types of cancer. IMFINZI may also cause the immune system to attack healthy cells.
Imfinzi and Keytruda work in a similar way to treat several forms of cancer. However, they're different in some of their side effects. And Keytruda is used to treat more types of cancer than Imfinzi. If you have questions about which drug may be better for your treatment plan, talk with your doctor.