KEY TAKEAWAYS
- The Phase III MONARCH-2 trial evaluated the effectiveness of Abemaciclib and Fulvestrant in advanced breast cancer patients.
- The primary aim was to examine the efficacy of Abemaciclib in addressing endocrine resistance in breast cancer patients regardless of PIK3CA or ESR1 mutations.
- The combination of Abemaciclib and Fulvestrant improved PFS and OS, with a slightly greater improvement in PFS in tumors.
- The study analyzed 219 and 248 patient samples for PIK3CA and ESR1 mutations, respectively.
- Abemaciclib, in combination with Fulvestrant, demonstrated efficacy in addressing endocrine resistance irrespective of PIK3CA or ESR1 mutation status
Mutations in PIK3CA and ESR1 have been associated with resistance to endocrine therapy in advanced breast cancer that is hormone receptor-positive and HER2-negative. The hypothesis suggested that inhibiting CDK4 and 6 could be a viable therapeutic approach for addressing endocrine resistance in individuals with breast cancers that have PIK3CA or ESR1 mutations. This preliminary examination aimed to evaluate the effectiveness of abemaciclib in conjunction with fulvestrant among patients, regardless of the presence of PIK3CA or ESR1 mutations in MONARCH 2.
The MONARCH-2 study was a double-blind, randomized phase III trial conducted worldwide. It involved 669 female patients diagnosed with hormone receptor-positive, HER2-negative advanced breast cancer who had previously undergone endocrine therapy and experienced disease progression. The study evaluated the efficacy of abemaciclib in combination with fulvestrant. The subjects were randomized in a ratio of 2:1 to receive either abemaciclib in combination with fulvestrant or placebo in combination with fulvestrant. The study conducted exploratory analyses to evaluate the progression-free survival (PFS) and overall survival (OS) as well as other endpoints in patients with or without detectable PIK3CA or ESR1 mutations in baseline circulating tumor DNA (ctDNA).
Out of the MONARCH-2 cohort, successful analysis of PIK3CA or ESR1 mutations was conducted on 219 and 248 patient samples, respectively. The combination of abemaciclib and fulvestrant improved progression-free survival (PFS) compared to placebo and fulvestrant. This improvement was observed in both PIK3CA-wild-type and PIK3CA-mutant subgroups, with a median PFS of 16.9 months versus 12.3 months (HR, 0.51; 95% CI, 0.33-0.78) and 17.1 months versus 5.7 months (HR, 0.53; 95% CI, 0.33-0.84), respectively. Additionally, both ESR1-wild-type and ESR1-mutant subgroups showed an improvement in PFS, with a median PFS of 15.3 months versus 11.2 months (HR, 0.44; 95% CI, 0.27-0.71) and 20.7 months versus 13.1 months (HR, 0.54; 95% CI, 0.37-0.79), respectively. Enhanced endpoints, comprising the operating system, were ameliorated after abemaciclib plus fulvestrant therapy, irrespective of PIK3CA or ESR1 mutation status.
The combination of abemaciclib and Fulvestrant demonstrated efficacy irrespective of the mutation status of PIK3CA or ESR1. The treatment resulted in improved progression-free survival (PFS) and overall survival (OS), with a slightly greater enhancement in median PFS as compared to the placebo plus Fulvestrant for tumors with PIK3CA or ESR1 mutations relative to their wild-type counterparts. This was observed in females diagnosed with hormone receptor-positive, HER2-negative advanced breast cancer that had advanced endocrine therapy.
Source: https://pubmed.ncbi.nlm.nih.gov/35121623/
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT02107703
Tolaney SM, Toi M, Neven P, Sohn J, Grischke EM, Llombart-Cussac A, Soliman H, Wang H, Wijayawardana S, Jansen VM, Litchfield LM, Sledge GW. Clinical Significance of PIK3CA and ESR1 Mutations in Circulating Tumor DNA: Analysis from the MONARCH 2 Study of Abemaciclib plus Fulvestrant. Clin Cancer Res. 2022 Apr 14;28(8):1500-1506. doi: 10.1158/1078-0432.CCR-21-3276. Erratum in: Clin Cancer Res. 2022 Oct 14;28(20):4587. PMID: 35121623.
