Both Imfinzi plus Lynparza and Imfinzi alone significantly improved progression-free survival of advanced endometrial cancer in combination with chemotherapy (2023)

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.

Comments

Endometriehylde
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

DUO-E
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
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
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.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-based biopharmaceutical company focused on the discovery, development and commercialization of prescription medicines in oncology, rare diseases and biopharmaceuticals, including cardiovascular, renal and metabolic medicines, and also preferably respiratory, focused and immunology. Headquartered in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. please visitastrazeneca.comand follow the company on Twitter@AstraZeneca.

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AstraZeneca PLC