On March 19, 2025, Health Canada approved KEYTRUDA® (pembrolizumab) in combination with carboplatin and paclitaxel, marking a significant advancement in the treatment of primary advanced or recurrent endometrial carcinoma. This decision stems from promising findings from the Phase 3 KEYNOTE-868 trial, which showcased substantial improvements in progression-free survival (PFS) for patients receiving KEYTRUDA® alongside chemotherapy compared to those administered a placebo along with the same standard treatment. Led by Dr. Alon Altman, Gynecologic Oncologist at the University of Manitoba, this innovative approach is garnering attention as it might address the pressing needs of many women battling this disease across Canada.
The KEYNOTE-868 trial, also known as NRG-GY018, is a rigorous multicenter, randomized, double-blind, placebo-controlled study that evaluated the efficacy of pembrolizumab when given with standard chemotherapy. A total of 810 patients were involved in the study, which stratified randomization considering mismatch repair (MMR) status and prior treatment exposures. Results indicated significant improvements in disease progression or survival rates, particularly among patients with deficient mismatch repair (dMMR) tumors, demonstrating a reduced risk of disease progression or death by 66% compared to placebo. Meanwhile, proficient mismatch repair (pMMR) patients experienced a reduced risk of 43%.
Pembrolizumab is uniquely positioned as an anti-PD-1 therapy, enhancing the immune system's ability to target tumorous cells. The approval of this drug follows a broader trend in oncology toward integrating immunotherapies to augment chemotherapy’s effects. This is particularly inspiring considering endometrial carcinoma is the fourth most common cancer among women in Canada, with an estimated 8,600 diagnoses expected in 2024 alone.
In parallel, advances in research are also noting promising developments with puxitatug samrotecan (P-Sam), an investigational antibody-drug conjugate (ADC) that targets tumors expressing B7-H4, a protein found in about 73% of endometrial cancers. Reported results from the BLUESTAR study revealed that P-Sam exhibited an objective response rate (ORR) of 34.6% and 38.5% for doses of 2 mg/kg and 2.4 mg/kg, respectively. Dr. Stéphanie Gaillard of Johns Hopkins Sidney Kimmel Cancer Center presented these findings at the Society of Gynecologic Oncology annual meeting, stating that the responses were observed across various levels of B7-H4 expression. Impressively, even patients with low B7-H4 expression levels achieved positive outcomes, paving the way for a planned Phase III trial to further assess P-Sam's efficacy against traditional chemotherapy options.
The BLUESTAR study has also highlighted the potential of P-Sam in advanced or metastatic endometrial cancer after patients received prior platinum-based therapy. Almost all participants (94%) had undergone such treatments. Doctors observed that treatment-related adverse events (TRAEs) affected around 83.3% of patients in the 2-mg/kg group, with gastrointestinal issues being the most common, but encouragingly, no treatment discontinuations were reported.
Distinctly, ongoing research by Boston Children's Hospital, led by Michael Rogers, PhD, and Victor Fattori, PhD, has revealed critical insights into the biology of endometriosis, a condition marked by the growth of uterine-like tissue outside the uterus. Current treatment modalities for this often painful condition remain largely unchanged over the past three decades, with many patients disillusioned by previous failed therapies.
Their recent study published in Science Translational Medicine noted significant interplay between the nervous and immune system in the pathology of endometriosis. By focusing on calcitonin gene-related peptide (CGRP), a factor released by pain-sensing neurons, the researchers discovered its role in amplifying inflammation and pathology of endometriosis lesions. By developing a mouse model simulating endometriosis, the team observed that blocking CGRP could minimize both lesion size and pain associated with the condition.
With CGRP inhibitors already approved for migraine treatments, Rogers and Fattori are now pursuing partnerships with pharmaceutical companies to launch clinical trials testing the efficacy of these treatments for endometriosis. Strengthening ties with clinical partners like Dr. Amy DiVasta, the efforts are targeted at developing acceptable treatment options for young patients dealing with this chronic and painful condition.
The collective momentum in research, clinical trials, and drug approvals presents a hopeful horizon for women facing endometrial cancer and endometriosis. The collaboration of healthcare professionals, researchers, and pharmaceutical companies is paving the way for innovative therapies that could enhance the quality of care and patient outcomes for women affected by these conditions.
