AstraZeneca Imfinzi plus chemotherapy gets USFDA nod for mismatch repair deficient advanced or recurrent endometrial cancer

The approval by the Food and Drug Administration (FDA) was based on the results of a prespecified exploratory subgroup analysis by MMR status in the DUO-E Phase III trial. Results from DUO-E were published in the Journal of Clinical Oncology.

In the trial, Imfinzi plus carboplatin and paclitaxel followed by Imfinzi monotherapy (Imfinzi arm) reduced the risk of disease progression or death by 58% in patients with dMMR endometrial cancer versus chemotherapy alone (hazard ratio 0.42; 95% confidence interval 0.22-0.80).

In the US, endometrial cancer is the fourth most common cancer in women, with more than 66,000 patients diagnosed and almost 12,000 deaths in 2022. Patients diagnosed at an early stage of disease have a five-year survival rate of approximately 80-90%, but there is a significant need for new treatment options for people with advanced disease, where the survival rate falls to less than 20%.

Shannon N. Westin, Professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, and principal investigator of the trial, said, “With the incidence and mortality of endometrial cancer expected to continue to increase significantly in the coming decades, it is more important than ever that we bring new treatment options to patients at the earliest possible moment in their care. This approval underlines clear evidence that durvalumab plus chemotherapy followed by durvalumab monotherapy delivers important clinical benefits for patients with mismatch repair deficient endometrial cancer.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said, “There have been limited advances in the treatment of endometrial cancer in the last few decades, and continued innovation is critical as the burden of this cancer is expected to grow in the future. Immunotherapy in combination with chemotherapy is emerging as a new standard of care in this setting, and the approval of Imfinzi offers an important new option for patients with mismatch repair deficient disease.”

The safety and tolerability profile of the Imfinzi and chemotherapy regimen was generally manageable, well tolerated and broadly consistent with prior clinical trials with no new safety signals.

The Lynparza (olaparib) and Imfinzi arm, which investigated Imfinzi plus chemotherapy followed by Imfinzi plus Lynparza as maintenance therapy, also met the primary endpoint of progression-free survival (PFS). The trial continues to assess OS as a key secondary endpoint for both arms. Regulatory applications for both Imfinzi as well as Imfinzi and Lynparza regimens are currently under review in the EU, Japan and several other countries based on the DUO-E results.

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.

In addition to its indications in unresectable, Stage III NSCLC and ES-SCLC, Imfinzi is currently approved in a number of countries in combination with a short course of tremelimumab (Imjudo) and chemotherapy for the treatment of metastatic NSCLC.

Imfinzi is also approved in a number of countries in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

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