KEY TAKEAWAYS
- The phase II study aimed to present the safety and effectiveness of pembrolizumab + mifepristone combo in advanced HER2-negative breast cancer.
- The primary endpoint was to measure the ORR, while the secondary endpoints were PFS, OS, DCR, safety, and tolerability.
- The study precludes a definitive assessment of mifepristone’s synergy with ICI.
Current breast cancer treatments are not very effective for metastatic disease. Combining immune checkpoint inhibitor (ICI) therapy with other treatments, such as GR antagonists, may be more effective.
Researchers aimed to present the safety and effectiveness of pembrolizumab + mifepristone combo in advanced HER2-negative breast cancer.
The study excluded prior ICI treatment recipients; patients(pts) received daily 300mg mifepristone and 200mg pembrolizumab every 3 weeks, with mifepristone preceding pembrolizumab by 7 days. Objective response rate (ORR) was the primary endpoint, while secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety, and tolerability.
Around 18 pts were enrolled, 10 with TNBC(cohort 1) and 8 with HR+ BC (cohort 2). Their mean age was 53 years (range: 33-74), with 33% self-reporting as Black. In cohort 1, 50% were treatment-naive in this advanced setting, and 90% had received <2 prior lines of treatment. In cohort 2, 25% hadn’t undergone prior chemo in the metastatic setting. The overall objective response rate (ORR) was 6%, with one TNBC patient achieving complete response (CR) and maintaining CR at >48 months post-treatment discontinuation due to mucositis and rash. Cohort 2 saw no partial or complete responses.
Prominent treatment-related adverse events (TRAEs) included rash (61%), thyroid abnormality (17%), and pruritus (17%). About 45% encountered grade 3 or 4 adverse events, excluding hypokalemia; these were rash-related, maculopapular dermatitis described as a rash. At 18 weeks, DCR reached 33.3% overall, with cohort 1 at 44.4% and cohort 2 at 16.7%. The median PFS stood at 1.9 months [95% CI 1.8 – 3.6] and the median OS at 12.9 months [95% CI 5.8 – 23.0].
The study precludes a definitive assessment of mifepristone’s synergy with ICI. Elevated skin toxicity, possibly due to mifepristone’s impact on ICI activity, prompted early termination; despite potential benefits, alternative chemotherapy-free immunomodulatory approaches merit exploration.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.1095
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03225547
Nan Chen, Elena Michaels, Poornima Saha, Murtuza M. Rampurwala, Olwen Mary Hahn, Frederick Matthew Howard, Gini F. Fleming, Theodore Karrison, Suzanne D. Conzen, and Rita Nanda. DOI: 10.1200/JCO.2023.41.16_suppl.1095 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 1095-1095.
