The FDA has granted accelerated approval to a new treatment strategy for certain people with advanced breast cancer—one that can begin after a resistance mutation appears in a blood test but before imaging shows that the cancer has progressed. Etcamah, also known as camizestrant, was approved September 4 in combination with one of three CDK4/6 inhibitors: abemaciclib, palbociclib or ribociclib. The treatment is specifically for adults with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who develop an ESR1 mutation while being treated with an aromatase inhibitor and CDK4/6 inhibitor.
A Blood Test Can Detect the Resistance Mutation
ESR1 mutations can develop as breast cancer adapts to treatment with aromatase inhibitors, a common form of endocrine therapy. According to the FDA, fewer than 5% of patients have these mutations when they’re initially diagnosed with HR-positive metastatic breast cancer. After the disease progresses on an aromatase inhibitor, however, nearly 40% may have an ESR1 mutation.
Etcamah’s approval introduces an important difference in when doctors can act. Instead of waiting until scans show that the cancer is progressing, physicians can use an FDA-authorized blood test to look for an ESR1 resistance mutation in circulating tumor DNA, or ctDNA.
This Is the First FDA Approval of Its Kind
Circulating tumor DNA consists of small pieces of DNA shed by tumors into the bloodstream. Analyzing that material can allow doctors to detect certain molecular changes occurring in a tumor through a blood sample.
FDA says Etcamah marks the first approval of a cancer therapy guided by detection of a resistance mutation in ctDNA before imaging shows disease progression.
Alongside the drug approval, FDA authorized the Guardant360 CDx assay as a companion diagnostic for identifying eligible patients with ESR1 mutations. That doesn’t mean every patient with advanced breast cancer should receive Etcamah or undergo the same treatment change. The approval applies to a specific group of patients meeting the cancer type, current-treatment and mutation requirements.
Patients Went Longer Before Their Cancer Progressed
FDA based the accelerated approval on results from the SERENA-6 clinical trial involving 315 patients. Participants had ER-positive, HER2-negative locally advanced or metastatic breast cancer with ESR1 mutations detected through circulating tumor DNA while receiving first-line treatment with an aromatase inhibitor and CDK4/6 inhibitor.
Patients hadn’t yet experienced disease progression when they entered the randomized portion of the study. One group switched from its aromatase inhibitor to Etcamah while continuing a CDK4/6 inhibitor. The comparison group continued taking an aromatase inhibitor with its CDK4/6 inhibitor.
Median progression-free survival was 16 months with Etcamah compared with 9.2 months for the group continuing aromatase inhibitor therapy.
Accelerated Approval Means Another Question Still Needs an Answer
The 16-month versus 9.2-month result is encouraging, but there’s an important limitation. FDA granted Etcamah accelerated approval based on progression-free survival measured from the time the ESR1 mutation was detected.
It hasn’t yet been confirmed that changing treatment at molecular detection—rather than waiting until conventional disease progression—is confirmed—ultimately produces a meaningful long-term clinical benefit. Overall survival data weren’t mature when the progression-free survival results were analyzed.
FDA has therefore required confirmatory studies to verify and further describe Etcamah’s clinical benefit. Continued approval for this indication may depend on those confirmatory results.
Etcamah Comes With Important Safety Warnings
Etcamah is an oral medication, with an FDA-recommended dose of 75 milligrams once daily with or without food. Treatment is combined with abemaciclib, palbociclib or ribociclib, with the CDK4/6 inhibitor generally continued at the same dosage being used when the ESR1 mutation was detected.
Etcamah’s prescribing information includes a boxed warning involving the risk of an abnormal heart rhythm caused by QTc interval prolongation when the drug is used with certain other medications that can also prolong QTc. Warnings and precautions also address bradycardia, or an abnormally slow heart rate, and potential harm to an unborn baby.
Patients shouldn’t make treatment changes based simply on an ESR1 test result without discussing the result, existing medications and potential risks with their oncology team.
What Patients and Families Should Ask About Testing and Coverage
The approval creates new questions for patients already receiving an aromatase inhibitor and CDK4/6 inhibitor for advanced breast cancer. Patients may want to ask their oncologist whether circulating tumor DNA monitoring is appropriate in their situation, how often testing would be considered and what an ESR1-positive result would mean for their treatment.
Insurance coverage for the companion diagnostic, Etcamah and the CDK4/6 drug used with it may also be important because the new approach involves both molecular testing and ongoing combination therapy. Patients should verify coverage and potential out-of-pocket costs before assuming an FDA approval means every component of treatment will automatically be covered by a particular health plan.
For families already facing the financial burden of metastatic cancer care, asking about prior authorization, specialty-pharmacy requirements and available financial assistance can be an important part of treatment planning. The scientific shift, however, is significant: doctors now have an FDA-approved option for certain patients that responds to a molecular warning sign of treatment resistance before traditional imaging confirms that the cancer has begun progressing.
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