Trial to Assess Alpelisib in Combination with Fulvestrant in PIK3CA-Mutated HR-Positive/HER2-Negative Advanced Breast Cancer

The SOLAR-1 study showed that the addition of alpelisib to fulvestrant led to a progression-free survival (PFS) benefit of 5.3 months in patients with PIK3CA-mutated HR-positive/HER2-negative advanced breast cancer; however, the efficacy of fulvestrant beyond progression in combination with alpelisib is unknown. In the phase 2 SEQUEL-Breast study, which aims to determine if treatment with fulvestrant beyond progression results in a clinically meaningful median PFS of ≥6 months, patients who progressed on CDK4/6 inhibitor and fulvestrant therapy may be treated with fulvestrant plus alpelisib.

The primary end point of SEQUEL-Breast is PFS, with secondary end points “on treatment” PFS, overall survival, objective response rate, clinical benefit rate, and duration of response. Mechanisms of resistance, the prognostic value of ctDNA, quality of life, and risk factors for alpelisib-induced hyperglycemia will also be assessed.

The SEQUEL-Breast trial (NCT05392608), which began in June 2022 and had enrolled 3 patients as of June 27, is a nationwide Dutch investigator-initiated phase 2 trial, with 25 centers expected to participate and target enrollment of 105 to 130 patients. The estimated trial length is 2 to 3 years, with the following eligibility criteria for patients:


BOOG Study Center acts as a sponsor for this trial. For additional information, please see NCT05392608.


Hamilton E, Spring L, Fasching PA, et al. SEQuence of endocrine therapy in advanced luminal breast cancer (SEQUEL-Breast): a phase 2 study on fulvestrant beyond progression in combination with alpelisib for PIK3CA-mutated, HR+ HER2- advanced breast cancer. San Antonio Breast Cancer Symposium 2022. Abstract OT2-01-08.

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