Insight From A Leading Clinician

  • As data from multiple trials continue to accumulate, Dr. Erica Mayer—an internationally recognized leader in breast cancer research and a co-author of the SERENA-6 trial evaluating the investigational oral SERD camizestrant—believes oral SERDs may represent not just an incremental advance, but a fundamentally stronger endocrine therapy with the potential to replace aromatase inhibitors and tamoxifen in select settings.
  • Dr. Sheheryar Kabraji, a breast oncologist and clinical researcher at Roswell Park Comprehensive Cancer Center, adds that oral SERDs have shown consistent improvements over prior endocrine therapies, particularly in endocrine-resistant disease, but that their activity as single agents remains modest.

How are breast oncologists using the new wave of oral medications to try and suppress estrogen, what has the field learned, and what’s next for this medication class?

In conversation with SurvivorNet, Dr. Erica Mayer, one of the nation’s leading clinical researchers and a breast oncologist at Dana-Farber Cancer Institute in Boston, shared her views on why enthusiasm around oral selective estrogen receptor degraders (SERDs) continues to build—and how emerging data suggest these agents may reshape endocrine therapy across the breast cancer spectrum.

Consistent Efficacy Across Multiple Trials

“The category of medicines called oral SERDs is really exciting because we are now seeing repetitively in multiple studies–EMERALD, EMBER-3, evERA and most recently in the early stage setting, lidERA—that oral SERDs are an effective treatment strategy, certainly for patients whose cancers have ESR-1 resistance mutations,” Dr. Mayer told SurvivorNet.

Across studies, Dr. Mayer explained, oral SERDs have demonstrated meaningful activity in patients with ESR-1 resistance mutations, while also showing promise in cancers without those mutations—particularly when paired with targeted agents. “We do expect or hope that we will have more FDA approvals of oral SERDs, and these will penetrate both the metastatic as well as the early stage setting,” she said.

Possible Benefits Beyond ESR-1–Mutated Disease

New data presented at the San Antonio Breast Cancer Symposium may further expand that role. Dr. Mayer highlighted results from the lidERA Breast Cancer (BC), a phase III adjuvant study of giredestrant vs. physician’s choice of endocrine therapy in early-stage disease. “Patients receiving giredestrant had a 30% improvement in preventing risk of disease recurrence,” she said, highlighting it as a striking finding in a population where ESR-1 mutations are uncommon.

A Broader Rethinking of Endocrine Therapy

Taken together, Mayer suggested the results may point to a broader conclusion: “Perhaps, what [these results] are telling us is the oral SERD is just a better drug than an aromatase inhibitor or tamoxifen.”

With multiple additional trials underway in both early and extended adjuvant settings, Mayer said more clarity is coming. “It’s going to be very exciting,” she said. “There are multiple other studies looking at oral SERDs in the early stage setting that we await results from both used upfront, such as in lidERA, as well as offered to patients during the extended period of time after they’ve been on endocrine therapy for a few years. So, there’s a lot more data to come in the early stage setting that will help refine and help us understand what role the oral SERDs will have.”


WATCH: Dr. Sheheryar Kabraji On The Limits, Efficacy And Future Directions Of Oral SERDs

Unlocking the Full Potential of Oral SERDs

Dr. Kabraji emphasized the importance of keeping expectations for oral SERDs grounded, highlighting that the use of oral SERDs as monotherapies has only delayed the progression of disease by  roughly three months. Where the field appears to be moving, he said, is toward combination strategies. “What we’re mostly seeing is that these oral SERDs when combined with other drugs are probably getting better disease control,” he said.

That evolution, Kabraji suggested, could ultimately reshape treatment sequencing in ER-positive metastatic breast cancer. “You’ll see third-based combinations becoming the sort of treatment of choice,” he said, describing a future in which endocrine backbones evolve earlier. “Instead of a standard endocrine therapy like Tamoxifen or an AI, they actually had that first-line therapy with SERD plus a CDK-4-6 inhibitor. And, then, subsequently we’ll have a targeted therapy with a second generation or advanced SERD.”

Ultimately, he explained, the aim is not simple substitution, but strategic repositioning. “That’s how we change the overall benefit of this class of drugs is not sort of keeping things static as they are, but continually sort of finding ways to bring our most effective treatments potentially earlier so that they can potentially control disease more effectively and for longer.”

“While it’s very attractive to have a monotherapy option for patients, those are fewer patients,” said Dr. Komal Jhaveri, a breast medical oncologist at Memorial Sloan Kettering Cancer Center and an author of the EMBER-3 trial of imlunestrant, speaking with SurvivorNet and adding context. “Not very many patients will be somebody with slowly progressing disease who are very endocrine sensitive who have this ESR-1 mutation.”