evERA Trial: What To Know
- The evERA breast cancer trial marks a turning point: an oral SERD-based combination that clearly outperforms standard endocrine + everolimus after CDK4/6 inhibitor therapy, particularly in tumors with ESR1 mutations.
- For patients, it means that when cancer has already outsmarted one line of hormone therapy, there may now be a new option, an all-oral regimen.
- The benefits compared to the standard are modest: median PFS was 8.77 months with giredestrant + everolimus vs. 5.49 months with standard endocrine therapy + everolimus. Still, it’s a welcome new option for a difficult to treat disease.
For people living with estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer, the pattern of treatment follows a very common path, typically starting on a hormone pill plus a CDK4/6 inhibitor. Things may go well for a while, and then the scans may show that cancer has grown again. At that point, many patients move to older endocrine drugs or combinations like exemestane plus everolimus — these options work, but often only for a limited time.
The evERA breast cancer trial is an important study testing something different: an all-oral, next-generation hormone strategy using giredestrant plus everolimus. Results show that this combination can keep the cancer controlled significantly longer than standard endocrine therapy plus everolimus in people whose disease has already progressed on a CDK4/6 inhibitor.
While experts SurvivorNet Connect spoke to do not consider this data groundbreaking, it’s a welcome new option for a difficult to treat disease.
“They’re still pretty modest benefits … but I do think it’s great to have more therapeutic options for our patients, particularly oral options,” Dr. Heather McArthur, Clinical Director of the Breast Cancer Program at Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, explains.
What Did evERA Find?
evERA is a phase 3, global, randomized trial in people with ER+, HER2- locally advanced or metastatic breast cancer. The patients had already been treated with a CDK4/6 inhibitor plus endocrine therapy (either in the metastatic or adjuvant setting) and their cancer had progressed on that treatment.
A total of 373 patients were randomized to either:
- Giredestrant + everolimus (all oral)
- Standard endocrine therapy (physician’s choice) + everolimus
Standard endocrine therapy typically meant an aromatase inhibitor like exemestane or other guideline-accepted options.
Giredestrant is an oral selective estrogen receptor degrader (SERD), a newer class of drugs that not only blocks the estrogen receptor but also marks it for destruction, which may help in tumors that have become resistant to older hormone pills.
The main outcome evERA looked at was progression-free survival (PFS). The trial showed:
- Median PFS was 8.77 months with giredestrant + everolimus vs. 5.49 months with standard endocrine therapy + everolimus.
- This translates to a 44% reduction in the risk of progression or death.
- In tumors with ESR1 mutations (a common resistance mutation after aromatase inhibitors) median PFS was 9.99 months in the giredestrant group vs. 5.45 months with standard endocrine + everolimus. That’s a 62% reduction in the risk of progression or death.
For patients whose cancer has already “broken through” a CDK4/6 inhibitor, evERA shows that an oral SERD-based regimen can almost double the time before the next progression, especially if the tumor carries an ESR1 mutation (one of the toughest resistance patterns we see).
Overall survival (OS) is still being followed. Early analyses show a “clear positive trend” favoring giredestrant + everolimus, but the data are not yet mature.
Still, the strong PFS improvement, especially in ESR1-mutant disease, is a big signal that this regimen is doing something clinically meaningful in a setting where options are limited.
Side Effects: What To Watch For
Because evERA added a new SERD but kept everolimus, the side-effect profile looks very similar to what we already know about everolimus-based regimens, with no new safety signals reported.
Common issues with everolimus-containing therapy include:
- Mouth sores (stomatitis)
- Fatigue
- Diarrhea
- Rash
- High blood sugar or high cholesterol
- Low blood counts
Giredestrant, as an endocrine drug, tends to carry side effects familiar from hormone therapy, such as hot flashes, joint aches, and mild GI symptoms, and was generally well tolerated with a safety profile consistent with prior endocrine therapies.
In evERA:
- The rates of adverse events were similar between arms
- No new or unexpected toxicities emerged
The combination was described as “well tolerated” in presentations and press materials.
For patients, this means the main trade-off is not about brand-new dangers, but about whether the added benefit in cancer control is worth accepting the known day-to-day burdens of an everolimus-based regimen (lab monitoring, mouth care, managing fatigue, and GI effects).
When To Offer This Regimen
When considering giredestrant + everolimus for a patient whose ER+/HER2– cancer has progressed on a CDK4/6 inhibitor, some questions are key, such as:
- Has this patient already had everolimus? evERA specifically studied people in the post-CDK4/6 setting, where everolimus is a common next step. For someone who hasn’t yet tried everolimus, the trial provides a strong rationale to use it with giredestrant rather than an older endocrine partner.
- Does the tumor carry an ESR1 mutation? Because the benefit was particularly large in ESR1-mutant disease (PFS ~10 vs ~5.5 months), patients whose circulating tumor DNA or tissue testing shows ESR1 mutations might be considered as candidates.
- Does an all-oral regimen fit the patient’s life? For many, the ability to avoid injections or infusions, travel less to infusion centers, and take pills at home is a real quality-of-life advantage, especially for people working, caregiving, or living far from major cancer centers.
