Camizestrant and continued remedy with CDK4/6 inhibition advantages sufferers who current with ESR1-mutated, ER+, HER2– superior breast most cancers: © inventory.adobe.com.
Amongst sufferers with sufferers with ESR1-mutated, estrogen receptor (ER)–constructive, HER2-negative superior breast most cancers, camizestrant plus continued remedy with CDK4/6 inhibition considerably improved progression-free survival outcomes in contrast with continued remedy with an aromatase inhibitor (AI) and CDK4/6 inhibitor when given previous to illness development on frontline remedy.
These findings have been derived from the part 3 SERENA-6 trial, information from which was shared in a press briefing on the 2025 ASCO Annual Assembly.
The median investigator-assessed progression-free survival was 16.0 months with camizestrant plus CDK4/6 inhibition (157 sufferers handled) versus 9.2 months with continued AI/CDK4/6 inhibition (158 sufferers handled). The 12- and 24-month progression-free survival charges within the camizestrant arm have been 60.7% and 29.7%, respectively, versus 33.4% and 5.4% within the continued AI/CDK4/6 inhibition arm.
“SERENA-6 is the primary international registrational part 3 examine to show the scientific utility of circulating tumor DNA [ctDNA] monitoring to detect and deal with rising resistance forward of illness development,” Dr. Nicholas C. Turner, lead examine creator and director of The Royal Marsden and Institute of Most cancers and Nationwide Institute for Well being and Care Analysis Biomedical Analysis Centre in London, United Kingdom, mentioned within the press briefing.
Echoing the importance of those findings, Dr. Eleonora Teplinsky,, acknowledged, “When sufferers progress on scans, we’re already behind. We’re switching remedy, and we’ve already misplaced management [of the disease]. What this examine does is [adopt] an early swap method earlier than we see illness development on imaging, permitting us to remain forward of the curve.” Teplinsky is head of Breast and Gynecologic Medical Oncology at Valley-Mount Sinai Complete Most cancers Care in Paramus, New Jersey, and a scientific assistant professor of medication at The Icahn Faculty of Drugs at Mount Sinai in New York, New York.
The Origin of the SERENA-6 Trial
Turner began the presentation by acknowledging the current unmet want for sufferers with ESR1-mutant, superior hormone receptor–constructive breast most cancers. Though uncommon at prognosis, comprising lower than 5% of superior circumstances, ESR1 mutations will develop in roughly 40% of circumstances, leading to illness development on frontline remedy with an AI and CDK4/6 inhibitor.
Nevertheless, ESR1 mutations could be remoted in ctDNA roughly 6 months earlier than development.
Camizestrant is a next-generation oral selective ER degrader and full ER antagonist that’s designed to inhibit and degrade the mutant and wild-type types of the ER. Beforehand, the FDA granted quick observe designation to the agent for the inhabitants enrolled in SERENA-6. By coupling the usage of ctDNA with early integration of camizestrant forward of illness development, investigators theorized they might delay the scientific good thing about frontline remedy.1
The randomized, double-blind, placebo-controlled SERENA-6 trial enrolled feminine and male sufferers with ER-positive, HER2-negative superior breast most cancers who had acquired no less than 6 months of an AI together with a CDK4/6 inhibitor as preliminary endocrine-based remedy for superior illness. Sufferers additionally wanted to have a detectable ESR1 mutation of their ctDNA with out proof of illness development.
A complete of three,325 sufferers who have been receiving frontline remedy with an AI and CDK4/6 inhibitor for no less than 6 months have been screened. ESR1 mutation testing (3,256 sufferers complete) was evaluated in ctDNA with the Guardant360 CDx assay each 2 to three months on the time of routine staging scans. A complete of 548 sufferers had detectable ESR1 mutations, 51% of whom have been constructive on the primary take a look at, 38% of whom have been constructive after two to 5 exams, and 11% of whom have been constructive after the fifth take a look at. A complete of 233 sufferers discontinued the examine resulting from screening failure (200 sufferers) or consent withdrawal, misplaced follow-up, or different causes (33 sufferers).
A complete of 315 sufferers have been randomly assigned to 75 milligrams (mg) of camizestrant each day plus continued CDK4/6 inhibition and placebo for the AI or continued AI with anastrozole or letrozole plus CDK4/6 inhibition and placebo for camizestrant. Remedy was continued till illness development, unacceptable toxicity, and affected person withdrawal or demise.
The first finish level was investigator-assessed progression-free survival by RECIST 1.1 standards. Secondary finish factors included time to second illness development or demise, general survival, security, and patient-reported outcomes.
Sufferers have been stratified by visceral illness (sure versus no), detection of ESR1 mutation (mutation detected at first take a look at versus a subsequent take a look at), time from initiation of CDK4/6 inhibition plus an AI to randomization (< 18 months versus ≥ 18 months), and selection of CDK4/6 inhibitor (Ibrance [Palbociclib] versus Kisqali [ribociclib] versus Verzenio [abemaciclib]).
Secondary Finish Factors and Trial Significance
Time to deterioration in international well being standing/high quality of life was additionally introduced. The median time to deterioration in line with the European Group for Analysis and Remedy of Most cancers 30-item high quality of life questionnaire was 23.0 months with camizestrant (107 sufferers) versus 6.4 months with continued AI/CDK4/6 inhibition (95 sufferers).
Turner famous that the camizestrant routine additionally had a low charge of remedy discontinuations ensuing from negative effects.
“[These data highlight the] potential for a brand new remedy technique in oncology to deal with creating resistance earlier than it causes development,” Turner mentioned in conclusion.
Elaborating on the novelty of the examine design, Teplinsky defined, “Permitting sufferers to stay on first-line endocrine remedy for hormone receptor–constructive, HER2-negative superior breast most cancers is essential, as a result of we all know that outcomes worsen with subsequent strains of remedy. Permitting that longer time on first-line endocrine remedy is critical, and it additionally improves high quality of life, as we’ve seen, and that’s an enormous a part of residing with metastatic breast most cancers. [The study] makes use of a know-how, [which] is a liquid biopsy, that doesn’t pose dangers of surgical biopsies, and it’s one thing that may be finished and is out there in our clinic now. Though camizestrant just isn’t but FDA authorised, this probably will pave the way in which for a brand new remedy technique in first-line hormone receptor–constructive, HER2-negative metastatic breast most cancers in sufferers with ESR1 mutations.”
Dr. Julie Gralow, chief medical officer and govt vice chairman at ASCO, added, “We’re utilizing these liquid biopsies [to detect] ctDNA. We’ve got complete periods at this assembly, taking a look at utilizing them in colon most cancers, however utilizing them to detect rising resistance earlier than we see proof of tumor development on scans is what’s novel about this examine.”
Reference
Turner N, Mayer E, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the remedy of emergent ESR1 mutations throughout first-line (1L) endocrine-based remedy (ET) and forward of illness development in sufferers (pts) with HR+/HER2– superior breast most cancers (ABC): Section 3, double-blind ctDNA-guided SERENA-6 trial. J Clin Oncol. 2025;43(suppl 17):LBA4. doi:10.1200/JCO.2025.43.17_suppl.LBA4
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