New Research from AstraZeneca Highlights the Lynparza Imfinzi Combination as Promising Solution for Unmet Endometrial Cancer Challenge

Cambridge, England – Latest analysis of the results from the DUO-E Phase III trial showed Imfinzi (durvalumab) plus platinum-based chemotherapy followed by Imfinzi plus Lynparza (olaparib) (Lynparza and Imfinzi arm) demonstrated an improvement in multiple key secondary efficacy endpoints, particularly in patients with mismatch repair proficient (pMMR) advanced or recurrent endometrial cancer compared to chemotherapy alone.

These results will be presented today in a late-breaking session at the 2024 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in San Diego, California.

A post-hoc exploratory subgroup analysis assessed patients by mismatch repair (MMR) status, a biomarker of interest in endometrial cancer. In this analysis, median duration of response (DoR) in pMMR patients in the Lynparza and Imfinzi arm was more than double versus the control arm (18.7 months versus 7.6). Additional secondary endpoints showed consistent results for pMMR patients treated with Lynparza and Imfinzi, demonstrating a reduction in the risk of second progression or death (PFS2) by 32% for the combination versus the control arm (median not reached versus 19.5 months, HR 0.68; 95% confidence interval [CI] 0.48-0.95), and improvement in time to first and second subsequent treatments.

Imfinzi plus chemotherapy followed by Imfinzi monotherapy (Imfinzi arm) showed consistent benefit regardless of MMR status, with the greatest benefit observed in patients with mismatch repair deficient (dMMR) disease across all secondary endpoints, including objective response rate (ORR) (71.4%) and DoR (median not reached), versus the control arm (40.5% and 10.5 months, respectively).

In the overall trial population, results in the Lynparza and Imfinzi arm showed extended ORR and DoR, as well as consistently improved benefit in secondary endpoints, including overall survival (OS), time to first subsequent therapy (TFST), PFS2 and time to second subsequent therapy (TSST).

Hye Sook Chon, gynaecologic oncologist at the Moffitt Cancer Center in Tampa, Florida, and trial investigator, said, “Endometrial cancer diagnoses are rapidly rising, yet very little has changed in recent years to advance new treatments for the approximately eighty per cent of patients with advanced or recurring disease who are mismatch repair proficient. DUO-E results demonstrate the benefit of durvalumab plus chemotherapy followed by durvalumab for patients with dMMR status and provide compelling evidence for the addition of olaparib to this regimen for patients with pMMR status.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “DUO-E results have shown that adding Imfinzi to chemotherapy delivers better outcomes for patients with advanced endometrial cancer. In addition, to achieve optimal clinical benefit for patients with the greatest unmet need – those with mismatch repair proficient disease – the addition of Lynparza further enhances the effect of checkpoint inhibition in endometrial cancer.”

Interim OS data showed a favourable trend for the Imfinzi arm and Lynparza and Imfinzi arm compared to the control arm in the overall trial population, irrespective of mismatch repair status.


Endometrial cancer
Endometrial cancer is a highly heterogeneous disease that originates in the tissue lining of the uterus and is most common in women who have already been through menopause, with the average age at diagnosis being over 60 years old.3-6 It is the sixth most common cancer in women worldwide.7 Incidence and mortality of endometrial cancer are expected to increase by approximately 61% and 87% respectively (from 420,400 cases and 97,700 deaths in 2022 to 676,300 cases and 183,100 deaths) in 2050.7,8

The majority of patients with endometrial cancer are diagnosed at an early stage of disease, where the cancer is confined to the uterus. They are typically treated with surgery and/or radiation, and the five-year survival rate is high (approximately 95%). Patients with advanced disease (Stage III-IV) usually have a much poorer prognosis, with the five-year survival rate falling to around 20-30%. Immunotherapy combined with chemotherapy is emerging as a new standard of care for advanced endometrial cancer, particularly for patients with dMMR disease, who make up approximately 20% of all patients with this type of cancer.9,10 There remains a high unmet need for treatments for the remaining 80% of endometrial cancer patients with pMMR disease.11,12


The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised, double-blind, placebo-controlled, multicentre Phase III trial of 1st-line Imfinzi (durvalumab) plus platinum-based chemotherapy (carboplatin and paclitaxel) followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) as maintenance therapy versus platinum-based chemotherapy alone as a treatment for patients with newly diagnosed advanced or recurrent endometrial cancer.

The DUO-E trial randomised 699 patients with newly diagnosed advanced or recurrent epithelial endometrial carcinoma to receive either Imfinzi (1120mg) or placebo, given every three weeks in addition to standard-of-care platinum-based chemotherapy. After 4-6 cycles of chemotherapy, patients (whose disease had not progressed) then received either Imfinzi (1500mg) or placebo every four weeks as maintenance, plus 300mg Lynparza (300mg BID [2x150mg tablets, twice a day]) or placebo until disease progression.

The dual primary endpoint was progression-free survival (PFS) of each treatment arm versus standard of care. Key secondary endpoints included overall survival (OS), safety and tolerability. Mismatch repair (MMR) status, recurrence status and geographic location were stratification factors. Mismatch repair deficient (dMMR) status reflects an inability to correct DNA replication errors and therefore results in an increased risk of cancer, while mismatch repair proficient (pMMR) status indicates when DNA repair pathways remain intact and where the mismatch repair pathway is active and functional.13,14 The trial was sponsored independently by AstraZeneca and conducted in 253 study locations across 22 countries including the US, Europe, South America and Asia.


Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is currently approved in a number of countries across multiple tumour types. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage small-cell lung cancer (SCLC) and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC.

In addition to its indications in lung cancers, Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma. Imfinzi is also approved in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. Imfinzi is also being tested as part of a broad development programme as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, ovarian cancer, several gastrointestinal cancers and other solid tumours.


Lynparza is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination-related (HRR) genes, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents [NHAs]).

Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza may also help enhance immunogenicity and increase the impact of anti-tumour immune responses.

Lynparza is currently approved in a number of countries across multiple tumour types, including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for germline BRCA mutation (gBRCAm), HER2-negative metastatic breast cancer (in the EU and Japan, this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in Japan, this includes all BRCAm HER2-negative high-risk early breast cancer); for gBRCAm metastatic pancreatic cancer; in combination with abiraterone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) when chemotherapy is not clinically indicated (EU only) and for BRCAm mCRPC (US and Japan); and as monotherapy for HRR gene-mutated mCRPC in patients who have progressed on prior NHA treatment (BRCAm only in the EU and Japan). In China, Lynparza is approved for the treatment of BRCA-mutated mCRPC as well as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer.

Lynparza is being jointly developed and commercialised by AstraZeneca and MSD, both as a monotherapy and in combination with other potential medicines. Independently, the companies are developing and will commercialise Lynparza in combination with their respective PD-L1 and PD-1 medicines, Imfinzi (durvalumab) and Keytruda (pembrolizumab). Lynparza has been used to treat approximately 140,000 patients worldwide. Lynparza has a broad clinical trial development programme, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.


AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.

AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi as monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also exploring next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer.

AstraZeneca is boldly pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.


AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.


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