Exploring the feasibility of treating newly diagnosed HR+/HER2- breast cancer patients with investigational endocrine agents — opening a path to more effective, less toxic care for women historically excluded from neoadjuvant chemotherapy trials.
In newly diagnosed breast cancer patients, women with certain HR+/HER2- tumors derive little benefit from neoadjuvant chemotherapy. Rates of pathologic complete response (pCR) are very low in this subtype, so patients with HR+/HER2- disease and chemo-resistant features are excluded from the I-SPY 2 breast cancer trial.
While there is no standard consensus treatment for this group — some receive chemotherapy, others endocrine therapy, others go directly to surgery — there is evidence that neoadjuvant endocrine therapy (NET) may effectively downstage tumors.
The I-SPY Endocrine Optimization Pilot (EOP) is a substudy of the I-SPY 2 trial that explores the feasibility of treating these women with investigational endocrine agents. Feasibility is defined as at least 75% of randomized patients completing at least 75% of assigned protocol therapy. Secondary endpoints include safety, efficacy, and exploratory biomarker endpoints — including Ki67, modified preoperative endocrine prognostic index (mPEPI), ctDNA, and MRI.
As a platform trial, EOP participants are treated with neoadjuvant amcenestrant (an oral SERD, or selective estrogen receptor degrader), given alone or in combination with one of several novel experimental endocrine therapies.
Multiple experimental agents can be efficiently and independently evaluated in parallel. Using a master protocol, agents can enter and leave the trial with a simple amendment.
A wide-ranging exploratory effort accompanies the study, with a goal of identifying new biomarkers to guide personalized treatment and contribute to the development of an early endpoint.
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Neoadjuvant chemo or targeted therapy is rarely successful in women with this type of early breast cancer. More effective, less toxic treatments are desperately needed.
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Patients newly diagnosed with stage II or III early breast cancer that is resistant to chemotherapy and may benefit from endocrine therapy — defined as HR+/HER2- and meeting one of the following:
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The SET index is an accurate and precise measure of the endocrine transcriptional activity in breast cancers.
EOP is open at I-SPY 2 sites across the United States. Talk to your doctor or contact a study coordinator at the site nearest you.
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