Camizestrant: A Better Option?
- Switching to a new drug combination — camizestrant plus a CDK4/6 inhibitor — soon after a blood test shows an emerging ESR1 mutation can keep metastatic HR+ breast cancer under control longer than the standard, new data shows.
- Camizestrant is beneficial for patients in other ways, too, as it is a small pill taken daily, reducing the need for patients to come in for treatment.
- “[The SERENA-6 trial] is a really important study in that it’s the first global, randomized phase III study that utilizes ctDNA guidance to direct therapy for patients,” Dr. Nancy Chan, director for breast cancer clinical research at NYU Langone Perlmutter Cancer Center, tells SurvivorNet Connect.
Good news for women and men facing hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer surfaced at the 2025 American Society of Clinical Oncology (ASCO) annual meeting in Chicago this week.
Researchers reported that switching to a new drug combination — camizestrant plus a CDK4/6 inhibitor — soon after a blood test shows an emerging ESR1 mutation can keep the cancer under control longer than the current standard approach with aromatase inhibitors and the same CDK4/6 backbone.
The promising findings came from the phase III SERENA-6 study, a clinical trial that enrolled people who had not yet experienced obvious progression on their first-line hormone therapy. The combination reduced the risk of disease progression or death by 56% in patients with HR+ breast cancer and an emerging ESR1 mutation — and SERENA-6 was the first study to demonstrate the value of closely monitoring circulating tumor DNA so cancer can be treated before progression shows up on scans.
Why The Data Matters
About 70% of patients with advanced breast cancer have hormone receptor positive disease. For these patients, the standard has been to start with an aromatase inhibitor such as letrozole or anastrozole, add a CDK4/6 inhibitor like palbociclib, then watch and wait — hoping the cancer stays quiet. Unfortunately, many tumors eventually outsmart aromatase inhibitors by picking up a change in the estrogen-receptor gene ESR1.
About one in three people on prolonged aromatase-inhibitor therapy will develop an ESR1 mutation.
Before the SERENA-6 trial, there was no proof that acting on the mutation early — as soon as a blood test detects the ESR1 mutation — would help patients live longer without disease progression. The trial offers the first high-level evidence that it does.
“SERENA-6 is a really important study in that it’s the first global, randomized phase III study that utilizes ctDNA guidance to direct therapy for patients,” Dr. Nancy Chan, director for breast cancer clinical research at NYU Langone Perlmutter Cancer Center, tells SurvivorNet Connect.
“… This trial actually implemented 8-week monitoring of a liquid biopsy, so it is monitoring the disease for a mutation called ESR1 every two months and should a patient develop an ESR1 mutation, then the therapy can change to an oral selective estrogen receptor degrader.”
Dr. Chan describes the approach as “staying ahead of changes at a mutational level in the blood and using that to guide early changes or interventions in therapy.”
Camizestrant: A Next-Generation SERD
Fulvestrant is an injectable SERD that has been used for many years after first-line treatment fails. Fulvestrant works well, but must be given as a monthly intramuscular shot, and its large-molecule design limits how much reaches metastatic sites such as the liver or lungs.
Camizestrant is different in several ways, including:
- It is a small pill taken once daily, so no clinic visits for injections.
- In laboratory models it was 50 to 100 times more potent at degrading both normal and mutant estrogen receptors.
- Early-phase trials hinted that camizestrant plus a CDK4/6 inhibitor could postpone tumor growth in people whose cancers already carried an ESR1 mutation.
