Roche’s giredestrant was shown to reduce the risk of breast cancer progression or death by 62% for a specific cohort of a phase 3 trial, as the pharma plans for the oral selective estrogen receptor degrader (SERD) to benefit “all comers.”
The evERA trial enrolled people with ER-positive, HER2-negative locally advanced or metastatic breast cancer who had previously received a CDK 4/6 inhibitor and endocrine therapy. Patients received the all-oral combination of giredestrant and Afinitor (everolimus) or standard of care.
Roche announced last month that the study hit its co-primary endpoints of demonstrating better progression-free survival (PFS) than standard of care in both the intention-to-treat (ITT) and ESR1-mutated populations. The Swiss pharma arrived at the European Society for Medical Oncology (ESMO) conference in Berlin this weekend armed with detailed data.
The findings tied giredestrant to 44% and 62% improvement in PFS for the ITT and ESR1 cohorts, respectively. Median PFS was 8.7 months in the ITT arm and 9.9 months in the ESR1-mutated population, compared to 5.4 months for the comparator arms.
While the most impressive data was from the ESR1-mutated patients, the pharma is confident that giredestrant will “work in all-comers,” according to Charles Fuchs, M.D., global head of oncology and hematology drug development.
“Our goal was—and still is—to make this drug available and useful for all-comers and across all settings of metastatic and curative settings of HR-positive breast cancer,” Fuchs told Fierce in an interview on the sidelines of the conference.
“When we look at overall survival, which is immature for the non-mutants, we see a hazard ratio and a trend that we think is clinically meaningful,” he added.
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It means that Fuchs and his team remain confident that giredestrant can take on the competition, such as AstraZeneca’s injectable SERD Faslodex, also known as fulvestrant.
“We think, in aggregate, the totality of the evidence says that giredestrant is better than fulvestrant, not only in the intent-to-treat and the mutants, but in the non-mutants,” he added. “And we believe this drug should be available in this setting, in this combination, for all patients.”
As part of this strategy, Roche is already evaluating giredestrant in four other late-stage breast cancer studies, including the persevERA trial for estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer, which is due to read out in the first half of next year.
Roche “feels good about” persevERA, according to Fuchs, who cited previous clinical evidence showing that “in a setting where the tumor is sensitive to ER, it does appear to be better.”
The data update at ESMO marks an ongoing return to favor for giredestrant after the drug contributed to a downturn in excitement about oral SERDs in 2022. That year, giredestrant failed a midphase breast cancer test, while Sanofi’s rival asset amcenestrant flunked a pivotal trial. The field has shifted again since then, with Menarini’s Orserdu coming to market in second-line patients and AstraZeneca’s camizestrant improving outcomes in first-line patients with emergent ESR1 mutations.
Looking back at that bump in the road for giredestrant, Fuchs described the failed breast cancer study as “really a high-risk bet in a population that was extremely endocrine-resistant.”
“So I think it was a useful phase 2 study,” he concluded. “We learned a lot from it … and we now have studies that I think are designed to test the right hypothesis.”
