Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment

by Selleckchem | Sep 12 2023

ESR1 mutation (ESR1m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. The aim is to treat ESR1m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety.

Comments:

The information you provided describes the background and objectives of the SERENA-6 study (NCT04964934), which is a randomized, double-blind, phase III clinical trial. The study aims to evaluate the efficacy and safety of switching from an aromatase inhibitor (AI) to camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), while maintaining the same cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) treatment in hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC).

In HR+/HER2- ABC, first-line therapy often involves the combination of an AI and CDK4/6i. However, one common cause of acquired resistance to this treatment is the presence of ESR1 mutations (ESR1m). Camizestrant is a novel SERD that has shown promise in a phase II study by significantly improving progression-free survival (PFS) compared to fulvestrant, another SERD, in ER+/HER2- ABC.

The primary objective of the SERENA-6 study is to assess the impact of switching from an AI to camizestrant, while maintaining CDK4/6i treatment, upon detection of ESR1 mutations in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. By targeting ESR1m clones, the goal is to prolong the control of estrogen receptor (ER)-driven tumor growth, thereby delaying the need for chemotherapy.

The primary endpoint of the study is progression-free survival (PFS), which measures the length of time during treatment that the disease does not progress or worsen. Secondary endpoints include chemotherapy-free survival, time to the second progression event (PFS2), overall survival, patient-reported outcomes, and safety. These secondary endpoints provide additional measures of the efficacy and safety of the treatment approach.

The study design is randomized and double-blind, meaning that participants will be randomly assigned to either the camizestrant or control group, and neither the participants nor the investigators will know which treatment they are receiving. This design helps minimize biases and ensures the integrity of the study results.

The SERENA-6 study aims to provide valuable data on the potential benefits of switching to camizestrant upon detection of ESR1 mutations in HR+/HER2- ABC, with the ultimate goal of improving patient outcomes and delaying the need for chemotherapy.