ESMO: Clear air emerges between Roche SERD and its rivals

Roche has taken a lead in the oral SERD category of breast cancer therapies with the presentation of new data at ESMO showing that the drug works as a second-line treatment for breast cancer, regardless of a patient's ESR1 mutation status.

Oncologists got the first opportunity for a look at the figures from the evERA study, toplined last month, which revealed that giredestrant given with everolimus improved progression-free survival (PFS) in patients with HR-positive, HER2-negative advanced breast cancer previously treated with CDK4/6 inhibitors and hormonal therapies compared to everolimus and standard care.

The combination reduced PFS by 44% and 62%, respectively, in the total study population and in the ESR1-mutated cohort, with a "clear positive trend" to increased overall survival in both groups.

"Resistance to standard-of-care therapies is common in the post-CDK inhibitor setting, and the results from evERA validate using a combination to address this challenge," said Dr Erica Mayer of the Dana-Farber Cancer Institute, who presented the results at ESMO.

"The clinically meaningful benefit observed with the giredestrant and everolimus all-oral combination is impressive and speaks to its potential to improve outcomes for patients in need of new treatment options."

That activity in the wild-type, non-mutated ESR1 population differentiates giredestrant from rivals in the oral SERD category, including the only FDA-approved representatives, Menarini's Orserdu (elacestrant) and Eli Lilly's Inluriyo (imlunestrant), which are labelled as monotherapies for use in ESR1-mutated patients only.

Arvinas and Pfizer's vepdegestrant – now shelved while a new partner is sought to take it forward – also failed to move the needle in wild-type ESR1 patients in the EMBER-3 trial.

"This is the first positive head-to-head phase 3 trial investigating a SERD-containing regimen versus a standard-of-care combination," said Roche in a statement that did not indicate whether the company anticipates getting an all-comer label from regulators.

The big question mark over the study is that it was enriched for ESR1 patients, accounting for more than half (55%) of recruited subjects, so it remains to be seen if the overall result will be considered strong enough for a broad label by regulators.

"A particularly high unmet need remains for people who become resistant to endocrine therapies and CDK inhibitors," said Roche's chief medical officer, Levi Garraway. "These study results support the potential for the giredestrant combination to become a new standard-of-care for all patients in this setting."

The company said that the evERA data will be shared with health authorities "with the aim of bringing this potential treatment option to people as soon as possible."