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Tanja Obradovic: News about effectiveness of PD-1 inhibitors in endometrial cancer continues to paint complex picture
May 15, 2024, 04:12

Tanja Obradovic: News about effectiveness of PD-1 inhibitors in endometrial cancer continues to paint complex picture

Tanja Obradovic

News about effectiveness of PD-1 inhibitors in endometrial cancer continues to paint complex picture.

Just announced negative read-out of Phase 3 KEYNOTE-B21 trial that evaluated Keytruda in combination with chemotherapy as adjuvant treatment, with or without radiotherapy, that did not meet its primary endpoint of disease-free survival (DFS) for the treatment of patients with newly diagnosed, high-risk endometrial cancer after surgery with curative intent contrasts some of the recent findings.

Another PD-1 inhibitor Jemperli just went under FDA consideration for expanded label to all endometrial patients regardless of dMMR and MSI-H status based on updated results of RUBY trial. This is after outstanding results for dMMR and MSI-H patients in RUBY trial by Jemperli and NRG-GY01820 with Keytruda where addition of these PD-1 inhibitors to chemotherapy, followed by PD-1 inhibitor maintenance in the first line delivered great benefits.

Staging in endometrial cancer now integrates molecular classification, tumor patterns, and histological staging so exploratory analysis across subgroups can be informative. Exploratory efficacy outcomes by molecular classification in RUBY, presented at ESMO 2023, showed clinical benefit (PFS and OS) with Jemperli plus Carboplatin–Paclitaxel in dMMR/MSI-H, mutant TP53, and no specific molecular profile molecular subgroups versus placebo plus Carboplatin–Paclitaxel (data based on the 400 patients for whom mutational data were available out of total 497 randomized).

Patients participating in KEYNOTE-B21 had high risk for recurrence following treatment with curative intent surgery, FIGO 2009 surgical stage I/II with myometrial invasion of non-endometrioid histology; FIGO 2009 surgical stage I/II with myometrial invasion of any histology with known aberrant p53 expression or p53 mutation; or FIGO 2009 surgical stage III or IVA of any histology and they could not have known DNA polymerase epsilon catalytic subunit A (POLE) mutation. It will be of interest to see if future reports on possible exploratory subpopulation analysis by histology or additional molecular entities reveal more information about outcome of the KEYNOTE-B21.”

Source: Tanja Obradovic/LinkedIn

Tanja Obradovic is the Vice President of Oncology Scientific Affairs at ICON PLCh. She has over 20 years of clinical research experience and has led major pharmaceutical companies for 13 years. Her research focuses on small molecules, antibodies, cell and gene therapy, and major immunotherapy of PD1 inhibitors.