AstraZeneca announced favorable results for its Imfinzi and Lynparza combo in an endometrial cancer study. The company reports that AZ’s Imfinzi, either alone or in combination with Lynparza, demonstrated superior performance compared to chemotherapy in preventing tumor growth or mortality in patients with newly diagnosed advanced or recurrent endometrial cancer.
The DUO-E trial’s favorable phase 3 readout comes only a few months after GSK’s Jemperli and Merck & Co.’s Keytruda both announced first-line endometrial cancer victories. However, AZ is the first to employ a PARP inhibitor, Lynparza.
Investigators in both Keytruda’s NRG-GY018 trial and Jemperli’s RUBY study employed each PD-1 inhibitor initially in conjunction with chemo and subsequently on its own as maintenance. In DUO-E, patients in the experimental arm also received Imfinzi and chemo at first. AZ, on the other hand, examined Imfinzi monotherapy or its combination with Lynparza throughout the study’s maintenance phase. Patients in the control arms received only the first chemotherapy as active treatment in all three studies.
Given that Imfinzi alone and with Lynparza demonstrated a substantial progression-free survival benefit over the chemo arm, doctors would like to know if Lynparza is required. For the time being, AZ stated that researchers found a “greater clinical benefit” from the combo. Based on what GSK and Merck have demonstrated for their immunotherapies, AZ will have a high bar to clear.
In the RUBY study, Jemperli demonstrated a significant 72% reduction in the risk of progression or mortality among patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors. In non-dMMR/MSI-H patients, the figure was 24%. After a very short follow-up period, Keytruda reduced risk by 70% in the dMMR/MSI-H group and 42% in the other patients in NRG-GY018.
In terms of whether the medications may help patients live longer lives, all three trials had yet to mature overall survival data. AZ stated that at this time, investigators had detected a favorable trend favoring the two Imfinzi regimens.
The endometrial cancer victory comes on the heels of a favorable phase 3 readout for the Imfinzi-Lynparza combination in ovarian cancer. In the DUO-O study, combining the combination with chemotherapy and Roche’s Avastin dramatically increased progression-free survival for newly diagnosed ovarian cancer without BRCA mutations.
However, the FDA has lately increased its scrutiny of the PARP inhibitor class, resulting in the loss of numerous indications. According to SVB Securities analyst Daina Graybosch, Ph.D., AZ will have a difficult assessment for the DUO-O indication. The detailed DUO-O results will be revealed on June 3 at the American Society of Clinical Oncology annual meeting in 2023. AZ also stated that it will discuss the new DUO-E statistics with authorities. On Lynparza, AZ collaborates with Merck; however, the two conduct separate trials when their PD-1/L1 inhibitors are involved.