Among the abstracts presented during General Session 3 at SABCS on Thursday, investigators shared findings from trials looking at the efficacy of the next-generation SERD camizestrant, the investigational AKT inhibitor capivasertib, and the use of circulating tumor cell count to guide the choice between chemotherapy and endocrine therapy.

GS3–02: Camizestrant, a next generation oral SERD vs fulvestrant in post–menopausal women with advanced ER–positive HER2–negative breast cancer: Results of the randomized, multi–dose Phase 2 SERENA–2 trial

Mafalda Oliveira, MD, PhD, Attending Physician in the Medical Oncology Department at the Vall d’Hebron University Hospital and the Breast Cancer Group at the Vall d’Hebron Institute of Oncology in Barcelona, Spain, presented findings from the phase II SERENA-2 trial, which showed that camizestrant improved progression-free survival, compared with fulvestrant, in patients with HR-positive, HER2-negative breast cancer.

Dr. Oliveira and her colleagues conducted the phase II SERENA-2 trial to determine whether patients with ER-positive breast cancer would benefit more from camizestrant or fulvestrant. Patients who were previously treated with no more than one prior endocrine therapy regimen and no more than one prior chemotherapy regimen were randomly assigned to receive fulvestrant or one of three dose levels of daily camizestrant: 75 mg, 150 mg, or 300 mg. The 300 mg arm was discontinued early due to strategic reasons, in the absence of toxicity concerns.

The 75 mg camizestrant arm, the 150 mg camizestrant arm, and the fulvestrant arms included 74, 73, and 73 patients, respectively. In the overall population, camizestrant significantly reduced the risk of disease progression or death by 42% at 75 mg and 33% at 150 mg, compared to fulvestrant. Patients treated with 75 mg of camizestrant and 150 mg of camizestrant had a median progression-free survival (PFS) of 7.2 months and 7.7 months, respectively, compared with 3.7 months for patients treated with fulvestrant.

Among patients with an ESR1 mutation, camizestrant reduced the risk of disease progression or death by 67% at the 75 mg dose (median PFS of 6.3 vs. 2.2 months) and by 45% at 150 mg (median PFS of 9.2 vs. 2.2 months). A reduction in the risk of disease progression or death was also observed in patients without a detectable ESR1 mutation, with a 22% reduction in risk at the 75 mg dose and a 24% reduction in risk at the 150 mg dose.

Camizestrant also demonstrated improved efficacy compared to fulvestrant in other high-risk patient subgroups, Dr. Oliveira reported. Those with lung and/or liver metastases experienced a reduction in the risk of disease progression or death of 57% for the 75 mg dose and 45% for the 150 mg dose, compared to fulvestrant. Patients who had been previously treated with CDK4/6 inhibitor therapy experienced a reduction in the risk of disease progression or death of 51% at the 75 mg dose and 32% at the 150 mg dose.

“The results of this study support further development of camizestrant in hormone receptor-positive breast cancer,” Dr. Oliveira said. “These results are noteworthy and may relaunch the enthusiasm for the development of oral SERDs in breast cancer.”

GS3–04: Capivasertib and fulvestrant for patients with aromatase inhibitor–resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: results from the Phase III CAPItello–291 trial

Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust in the United Kingdom, shared findings from the phase III CAPItello-291 clinical trial demonstrating that, in patients with HR-positive, HER2-negative tumors resistant to aromatase inhibitors, addition of the investigational AKT inhibitor capivasertib to fulvestrant doubled the median progression-free survival compared with placebo plus fulvestrant.

Dr. Turner and colleagues conducted the phase III CAPItello-291 trial to determine whether the addition of the potential first-in-class AKT inhibitor capivasertib to fulvestrant would improve outcomes in patients with HR-positive breast cancer whose tumors had developed resistance to an aromatase inhibitor. The researchers randomly assigned 355 patients to receive capivasertib plus fulvestrant and 353 patients to receive a placebo plus fulvestrant.

Patients treated with capivasertib plus fulvestrant had a median progression-free survival of 7.2 months, compared to 3.6 months in patients treated with placebo plus fulvestrant. This amounted to a 40% lower risk of progression among patients who received capivasertib plus fulvestrant. The objective response rate was 22.9% among patients treated with capivasertib plus fulvestrant, compared with 12.2% for patients treated with placebo plus fulvestrant.

Overall, 41% of patients assigned to treatment had tumors with AKT pathway mutations. Among patients with AKT pathway mutations treated with capivasertib plus fulvestrant, the median progression-free survival was 7.3 months, and the objective response rate was 28.8%. Among patients with AKT pathway mutations treated with placebo plus fulvestrant, the median progression-free survival was 3.1 months, and the objective response rate was 9.7%.

“The improvement in progression-free survival with relatively well-tolerated side effects is extremely encouraging,” Dr. Turner said. “We are hopeful that capivasertib will become a new treatment option for patients whose cancer has progressed on a regimen containing an endocrine therapy.”

GS3–09: Circulating Tumor Cells–driven choice of first line therapy for ER+ HER2– metastatic breast cancer: overall survival analysis of the randomized STIC CTC trial

François-Clément Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie and Versailles Saint-Quentin University in Paris, presented data from the STIC CTC trial showing that the use of circulating tumor cell (CTC) count to guide the choice between chemotherapy and endocrine therapy as first-line therapy for patients with metastatic, ER-positive/HER2-negative breast cancer provided overall survival benefit, compared with physician’s choice of treatment.

To test the ability of the CTC count to improve patient outcomes when used to drive the treatment decision between chemotherapy and endocrine therapy in women with metastatic, ER-positive/HER2-negative breast cancer, Dr. Bidard and colleagues designed the STIC CTC trial, in which 755 patients were randomly assigned (1:1) to having their treatment decided by the investigator or by their CTC count.

The primary results of this trial, reported at SABCS in 2018, showed a progression-free survival benefit in patients whose treatment was escalated from endocrine therapy to chemotherapy based on their CTC count. After a follow-up of nearly five years, the authors now report the overall survival analysis of the trial, showing that, in patients with discordant recommendations between the investigator’s choice of therapy and the CTC count, the strategy based on CTC count resulted in better long-term outcomes.

Among a subgroup of patients representing 25% of the study population, for whom endocrine therapy was the recommended treatment by investigator’s choice but who displayed high CTC count, those who were treated with chemotherapy had an absolute gain of 16 months in median overall survival and experienced a 47% reduction in their risk of death compared to patients in the same group who received endocrine therapy.

Among the subgroup of patients who were assigned to chemotherapy by investigator’s choice but had low CTC count, corresponding to 14% of the study population, those who received endocrine therapy had a comparable overall survival to those who received chemotherapy.

“The STIC CTC trial is the first to establish the clinical utility of the CTC count as a biomarker in breast cancer care, indicating that a single assessment of the CTC count before the start of treatment can guide the treatment decision between chemotherapy and single-agent endocrine therapy in ER-positive/HER2-negative metastatic breast cancer,” said Dr. Bidard. “Our study demonstrates that integrating prognostic biomarkers into the treatment algorithm can improve the management and outcomes of metastatic breast cancer patients.”