Developing Story: The Camizestrant Vote — When Your Blood Test Knows Before Your Scan Does
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Live from Stage 4 | Episode #029 | 05/19/2026 | Developing Story
Panel
Lynda Weatherby -- living with MBC since 2013 after 2001 DCIS, a Seattle-based patient advocate and advocate founder of “The Project to End Postpartum Breast Cancer."
Ellen Landsberger, MD -- a retired OB/GYN from New York has lived with metastatic breast cancer for years, but it was the loss of a close friend to the disease that sparked her interest in using her voice to help educate others.
Jill Tirabassi, MD -- researcher and advocate, and another physician on our team, diagnosed with breast cancer during her second pregnancy at the age of 36, she now works part-time while raising her two young sons with her husband outside of Buffalo, New York
Abigail Johnston lives in Orlando, Florida and has been an attorney since 2002. In 2017, while tandem breastfeeding her boys (then 1 and 3), Abigail was diagnosed with de novo Stage IV Metastatic Breast Cancer (MBC) and soon thereafter discovered that she has a genetic mutation that predisposed her to developing cancer at ATM. Since her diagnosis, Abigail has focused her efforts on patient advocacy and supporting those people in the MBC Community through her experience and training, virtually and in person. She currently serves as the Director of Mentorship, Legal Clinics and financial services at Project Life, a founding member of the PIK3CA Pathbreakers, and volunteers with a variety of organizations including the MBC Alliance, FORCE, METAvivor, and many others. Connect with Abigail via her blog at NoHalfMeasures.blog.
Janice Cowden is a prominent American metastatic breast cancer (MBC) patient research advocate, key opinion leader, and retired pediatric nurse. Diagnosed with stage IV triple-negative breast cancer in 2016, she transitioned from a 20-year career in nursing and pharmaceutical sales into a powerful force in oncology advocacy. She focuses on bridging the knowledge gap between patients and healthcare teams, championing patient-centered dosing, and defending federal research funding
. Dr. Kelly Shanahan, M.D. is a prominent metastatic breast cancer patient advocate who serves as the President of the Board of Directors for METAvivor Research and Support. Diagnosed with widespread bone metastasis on her 53rd birthday in 2013, she transitioned from a successful career as an obstetrician-gynecologist to a full-time force in cancer advocacy after severe treatment-induced neuropathy forced her to stop practicing medicine
Quick Summary
In this episode, host Victoria Goldberg brings together six leading metastatic breast cancer patient advocates to unpack the FDA advisory committee's 6-3 vote against recommending camizestrant in the SERENA-6 trial setting. The panel makes clear that this was not a vote against the drug itself, but against the idea of switching therapy based on molecular progression alone before the evidence is strong enough to support it.
The conversation covers the trial's design flaws, the ongoing debate over progression-free survival versus overall survival as endpoints, and what the emergence of an ESR1 mutation on a liquid biopsy actually means for treatment decisions. The panel also digs into who has access to these tests, the wide gap between academic and community oncology, and why patient advocates need to be at the table when trials are designed, not after the fact.
The takeaway from every voice in this conversation is the same: camizestrant is a promising drug, the science of molecular progression is moving fast, and the field just needs more data, better trial design, and more patients in the room from the very beginning.
Key Topics Covered
What the ODAC 6-3 vote actually means for camizestrant and the SERENA-6 trial
Why this was a vote against early switching, not against the drug itself
Trial design flaws and the missing crossover arm
Progression-free survival vs. overall survival as endpoints
Molecular progression vs. radiologic progression and whether ctDNA alone should drive treatment decisions
The risk of burning through lines of therapy by switching too early
Quality of life data and why it should have been a primary endpoint
Insurance coverage gaps for liquid biopsy testing
The two-tier care system between academic and community oncologists
Why patient advocates need to be involved in trial design from the start, not after IRB approval
What comes next for camizestrant and the broader SERENA program
Terms Glossary
ODAC (Oncologic Drugs Advisory Committee) A panel of independent experts that advises the FDA on whether a drug should be approved. The FDA usually, but not always, follows their recommendations.
FDA Advisory Vote The formal vote by ODAC recommending for or against approval of a drug. In this case the committee voted 6-3 against recommending camizestrant for the specific use tested in SERENA-6.
Phase II vs. Phase III Trial Phase II trials are smaller, earlier-stage studies that test whether a drug shows enough promise to move forward. Phase III trials are larger, more definitive studies designed to confirm effectiveness. SERENA-6 was a Phase III trial.
Progression-Free Survival (PFS) How long a patient lives without their cancer growing or spreading. Used as a trial endpoint when overall survival data would take too long to collect.
Overall Survival (OS) How long a patient lives after starting treatment. Considered the gold standard endpoint but requires longer follow-up to measure.
PFS2 A secondary endpoint that measures how long a patient survives without progression through their next line of treatment after the trial drug. It was introduced in SERENA-6 to try to capture longer-term benefit.
Crossover When patients in the control arm of a trial are allowed to switch to the investigational drug after their disease progresses. The lack of a structured crossover in SERENA-6 was one of the panel's main criticisms of the trial design.
ESR1 Mutation A genetic change in the estrogen receptor gene that can develop during treatment with aromatase inhibitors. Its emergence on a liquid biopsy was the trigger for early switching in SERENA-6.
Molecular Progression When a biomarker like an ESR1 mutation appears or rises in a blood test, suggesting the cancer may be becoming resistant, even before any visible changes show up on imaging.
Radiologic Progression When cancer growth or spread is confirmed on a scan such as a CT or bone scan. Traditionally the standard for declaring that a treatment has failed.
Liquid Biopsy A blood test that detects tumor DNA circulating in the bloodstream. Used to identify mutations like ESR1 without requiring a tissue biopsy.
ctDNA (Circulating Tumor DNA) The fragment of tumor DNA found in a blood sample. Rising ctDNA levels or new mutations can signal that a cancer is changing or becoming resistant to treatment.
Tumor Allele Fraction The percentage of ctDNA in a blood sample that carries a specific mutation. A key detail discussed in the episode as more informative than simply knowing whether a mutation is present or absent.
Signatera A tumor-informed liquid biopsy test that requires a tissue sample to personalize what it looks for. Discussed in the episode in the context of insurance coverage and access limitations.
Guardant 360 and Guardant Reveal Liquid biopsy tests that do not require prior tissue. Guardant 360 is used primarily to detect mutations at progression. Guardant Reveal is more focused on minimal residual disease monitoring.
MRD (Minimal Residual Disease / Molecular Residual Disease) Tiny amounts of cancer remaining after treatment that are too small to detect on scans but can sometimes be found through sensitive blood tests.
PROs (Patient-Reported Outcomes) Data collected directly from patients about how they feel and function during a trial, including quality of life, side effects, and daily impact. The panel argued these should be primary endpoints, not secondary ones.
Primary vs. Secondary Endpoints A primary endpoint is the main question a trial is designed to answer. Secondary endpoints are additional measures tracked alongside it. Quality of life was only a secondary endpoint in SERENA-6, which the panel felt limited its weight in the ODAC decision.
IRB Approval (Institutional Review Board) The ethics review process a trial must pass before it can begin. Several panelists noted that patient advocates are often only consulted after IRB approval, which is too late to influence the core design.
SERENA-6, SERENA-2, PADA-1, SONIA Clinical trials referenced in the episode. SERENA-6 tested early switching to camizestrant based on ESR1 emergence. PADUA-1 tested a similar early switch concept using fulvestrant. SONIA examined whether adding a CDK4/6 inhibitor upfront is always necessary. SERENA-2 is an ongoing trial looking at camizestrant in combination with other agents.
CDK4/6 Inhibitors A class of drugs commonly used in hormone receptor-positive MBC, including palbociclib, ribociclib, and abemaciclib. The episode discusses what sequential use of these drugs means for patients and how that parallels the debate over sequential oral SERDs.
Oral SERDs (Selective Estrogen Receptor Degraders) A newer class of drugs that degrade the estrogen receptor, taken as a pill rather than an injection. Camizestrant, elacestrant, imlunestrant, and vepdestrant are all oral SERDs discussed in this episode.
Aromatase Inhibitors (AI) Drugs like letrozole and anastrozole that lower estrogen levels and are commonly used as first-line treatment in hormone receptor-positive MBC. SERENA-6 patients were on an AI plus a CDK4/6 inhibitor before the switch.
Clinical Trial Endpoints
Clinical endpoints are the "yardsticks" doctors use to see if a new cancer drug is safe and effective. While living longer (Overall Survival) is the most important goal, it takes a long time to measure. Because of this, researchers are increasingly using faster "stand-in" measures (surrogate endpoints) to get results sooner.
They are also looking at other factors, like how a patient feels (quality of life) and why a treatment might stop working. As new treatments like immunotherapy emerge, these measuring tools are evolving to give a more complete picture of how a drug helps a patient.
References
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics: Guidance for Industry
Clinical endpoints in oncology - a primer
Overall survival (OS)
Time from randomization or treatment start until death from any cause.
Considered the most definitive endpoint because it directly measures length of life.
Often the strongest basis for traditional approval when feasible, but it may be hard to use in some cancers because of long follow-up, crossover, or effective subsequent therapies.
Progression-free survival (PFS) / time to progression (TTP)
Measures how long a patient lives without tumor growth or worsening, or until documented progression.
Useful whenwaiting for OS would take too long or be confounded by later treatments.
Can support approval in settings where progression is closely linked to patient benefit, but the FDA treats itas a surrogate rather than a direct clinical benefit endpoint.
Objective response rate (ORR)
The proportion of patients whose tumors shrink by a predefined amount.
Especially important in single-arm studies and accelerated approval settings,where a substantial and durable response may indicate meaningful activity.
The guidance notes that low or modest response rates are generally not persuasive evidence of benefit.
Duration of response (DoR)
How long a confirmed tumor response lasts.
Important because response rate alone is not enough; durability helps show that the benefit is real and clinically meaningful.
Disease-free survival (DFS) / event-free survival (EFS)
Used mainly when the intent is to measure time until recurrence, relapse, or another defined event after treatment.
More common in settings such as adjuvant therapy rather than advanced disease.
These endpoints can support regulatory decisions when they reflect meaningful delay in clinically importantevents.
Time to treatment failure / symptom endpoints/ quality of life
Time to treatment failure captures stopping therapy for progression, toxicity, or death.
Symptom endpoints and patient-reported outcomes are important when a treatment’s valuedepends on relief of cancer-related symptoms or preservation of function.
The guidance treats these as valuable but methodologically challenging, and they require careful measurement.
Time to Drug Failure" (TDF) is not a standardized or universally recognized regulatory endpoint. Instead, it is typically used interchangeably with established time-to-event metrics, most commonly Time to Treatment Failure (TTF)
Clinical Studies Mentioned
SERENA-6, the central trial of this discussion. A Phase III randomized study by AstraZeneca testing camizestrant, an oral SERD in patients with HR-positive, HER2-negative metastatic breast cancer on first-line aromatase inhibitor therapy. Patients were randomized at the point of ESR1 mutation detection before radiographic progression to either continue standard care or switch early to camizestrant. The trial met its primary endpoint of PFS, showing a roughly six point eight months benefit. ODAC voted six-three not to recommend approval, citing concerns about trial design, the lack of overall survival data, and the absence of a structured crossover.
PADa-1, a French Phase II trial that also explored early switching based on ESR1 mutation emergence. Patients on palbociclib plus an aromatase inhibitor were monitored with liquid biopsy. Those who developed a rising ESR1 mutation were randomized to either switch to fulvestrant plus palbociclib or continue their current therapy until radiographic progression with crossover allowed. PADA-1 is smaller than SERENA-6, but is considered better designed in some respects precisely because of that crossover provision. It helped establish proof of concept for the early switch strategy, though its data on overall survival remains immature.
SONIA, a Dutch phase III trial that tested a different but related question: Does it matter whether you use a CDK4/6 inhibitor in the first line of treatment or the second? SONIA found that starting with an aromatase inhibitor alone and adding a CDK4/6 inhibitor as a second line produced similar overall survival to starting with both upfront, challenging the assumption that CDK4/6 inhibitors must always be part of the first-line therapy. Kelly referenced this as an evidence that the field has more confounding data than it realizes, and that the optimal sequencing of these drugs is still genuinely unsettled.
SERENA-2, an earlier phase II dose-finding and efficacy study for camizestrant in previously treated HR-positive, HER2-negative metastatic breast cancer. It established camizestrant's activity and helped determine the doses used in SERENA-6. Kelly references several ongoing SERENA trials as evidence that camizestrant's development continues despite the ODAC setback.
VERITAC-2: a Phase III study of vepdegestrant, a PROTAC ER degrader, versus fulvestrant in ER+/HER2- advanced breast cancer
