by Hope S Rugo, Florence Lerebours, Eva Ciruelos, Pamela
Drullinsky, Manuel Ruiz-Borrego, Patrick Neven, Yeon Hee Park, Aleix Prat,
Thomas Bachelot, Dejan Juric, Nicholas Turner, Nickolas Sophos, Juan Pablo
Zarate, Christina Arce, Yu-Ming Shen, Stuart Turner, Hemanth Kanakamedala,
Wei-Chun Hsu, Stephen Chia
The Lancet Oncology: VOLUME 22,
ISSUE 4, P489-498, APRIL 01, 2021
Background
Alpelisib, a PI3Kα-selective inhibitor and degrader, plus
fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated
advanced breast cancer in SOLAR-1; limited data are available in the
post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess
alpelisib plus endocrine therapy in this setting in three cohorts defined by
immediate previous treatment; here, we report results from cohort A.
Methods
This ongoing, phase 2, multicentre, open-label,
non-comparative study enrolled patients with hormone receptor-positive,
HER2-negative, advanced breast cancer with tumour PIK3CA mutation,
following progression on or after previous therapy, including CDK4/6
inhibitors, from 114 study locations (cancer centres, medical centres,
university hospitals, and hospitals) in 18 countries worldwide. Participants
aged 18 years or older with an Eastern Cooperative Oncology Group performance
status of 2 or less, with no more than two previous anticancer treatments and
no more than one previous chemotherapy regimen, were enrolled in three cohorts.
In cohort A, patients must have had progression on or after a CDK4/6 inhibitor
plus an aromatase inhibitor as the immediate previous treatment. Patients
received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg
intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The
primary endpoint was the proportion of patients alive without disease
progression at 6 months per local assessment using Response Evaluation Criteria
in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation.
This trial is registered with ClinicalTrials.gov, NCT03056755.
Findings
Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127
patients with at least 6 months' follow-up were enrolled into cohort A. 121
patients had a centrally confirmed PIK3CA mutation. At data cutoff,
median follow-up was 11·7 months (IQR 8·5–15·9). 61 (50·4%; 95% CI 41·2–59·6)
of 121 patients were alive without disease progression at 6 months. The most
frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127
patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse
events occurred in 33 (26%) of 127 patients. No treatment-related deaths were
reported.
Interpretation
BYLieve showed activity of alpelisib plus fulvestrant with
manageable toxicity in patients with PIK3CA-mutated, hormone
receptor-positive, HER2-negative advanced breast cancer, after progression on a
CDK4/6 inhibitor plus an aromatase inhibitor.
