Roche's oral SERD comes good in 2nd-line breast cancer trial

Roche has staked a claim to use its oral selective oestrogen receptor degrader (SERD) giredestrant as a second-line therapy for breast cancer, regardless of a patient's ESR1 mutation status.

Top-line results from the evERA study showed that the combination of giredestrant 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 standard care plus everolimus.

There was also a "clear positive trend" to improved overall survival (OS) with giredestrant, said Roche, which is hoping to file for approval of the drug in this setting based on the data.

Crucially, the evERA result showed efficacy for the drug both in an ESR1-mutated patient population and in allcomers and, according to Roche, it is the first phase 3 trial of an all-oral SERD-containing therapy to better a standard-of-care combination.

Current second-line options include injectable SERD fulvestrant, as well as aromatase inhibitors like letrozole, anastrozole, or exemestane.

It's worth noting that the patient population in the trial was enriched for people with ESR1 mutations, so, for now, it is not clear if the overall intent-to-treat result will support an all-comer label if giredestrant is approved for marketing. There's no word yet on patients with wild-type ESR1.

The result marks something of a comeback for giredestrant, which failed the phase 2 acelERA trial in previously treated HR+/HER2- breast cancer in 2022. It also comes after another drug in the oral SERD category – Sanofi's amcenestrant – has been abandoned, while Arvinas and Pfizer are seeking to hand off their candidate vepdegestrant to another developer, after reporting disappointing clinical results.

One drug in the class – Menarini's Orserdu (elacestrant) – is already approved for second-line treatment of this type of breast cancer, though in ESR1-mutated patients only, and vepdegestrant is under FDA review for a similar indication, with a decision due next June.

Meanwhile, AstraZeneca recently reported encouraging first-line data with its oral SERD camizestrant in the SERENA-6 trial.

Roche is also gunning for a first-line all-comer indication for giredestrant in HR+/HER2- breast cancer based on the results of the persevERA study and adjuvant use in lidERA, with both trials due to read out next year. AZ is also looking at adjuvant treatment with camizestrant in the CAMBRIA-1 and CAMBRIA-2 studies, as is Menarini with its ELEGANT trial.

"Data from the evERA study will be submitted to health authorities with the view of bringing this potential treatment option to patients as soon as possible," said Roche in a statement.