The U.S. approval of camizestrant gives some patients a treatment-switch option before scans show progression, as managed-care stakeholders report uncertainty over when to test for ESR1 mutations.
An October paper in the Journal of Managed Care & Specialty Pharmacy summarizes a virtual discussion convened in February by the Academy of Managed Care Pharmacy (AMCP). The panel examined testing practices; its discussion was not a clinical trial and was not intended to set a formal standard. AMCP estimates that ESR1 gene mutations develop after initial endocrine treatment in nearly half of patients with hormone receptor-positive metastatic breast cancer. Blood tests that look for circulating tumor DNA (ctDNA) may identify some mutations before scans show progression, creating an opportunity to consider a treatment change.
SERENA-6 used ctDNA tests at intervals of two to three months. Of 3,256 patients tested, 315 had an ESR1 mutation without radiologic progression and were randomly assigned to switch to camizestrant or remain on an aromatase inhibitor. Both groups also received a CDK4/6 inhibitor. After a median follow-up of 12.6 months, median progression-free survival was 16.0 months with camizestrant and 9.2 months with the aromatase inhibitor. The trial schedule does not establish a routine-care testing interval.
On Sept. 4, the U.S. Food and Drug Administration (FDA) granted accelerated approval for camizestrant with abemaciclib, palbociclib or ribociclib for adults with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer. The ESR1 mutation must be detected during aromatase inhibitor and CDK4/6 inhibitor treatment using an FDA-authorized test. The agency also approved Guardant360 CDx as a companion diagnostic. At the progression-free-survival analysis, overall-survival follow-up was still immature. The FDA said confirmatory evidence of clinical benefit may be needed to maintain the accelerated approval.
The FDA approved vepdegestrant on May 1 for adults with ESR1-mutated, estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer after progression following at least one line of endocrine therapy.
Kirollos Hanna, director of pharmacy at Minnesota Oncology and an AMCP panelist, said oncology pathways and prior-authorization processes often use imaging results, while blood tests may identify mutations earlier. “The ideal future state is not more testing. It’s more purposeful testing connected to timely evidence-based action,” he said in an AMCP interview. The interview discussed potential burdens of repeat testing, including patients’ time and costs, and separately highlighted quality of life and independence as outcomes patients value.
AstraZeneca funded the AMCP program and sponsored the podcast interview. Co-author Carol Tweed disclosed consulting fees from AstraZeneca and participation in its U.S. camizestrant steering committee. The FDA identified confirmation of clinical benefit as a possible condition for continued approval but did not provide a timetable.
