Menarini is late to go early with Orserdu

Menarini’s Orserdu remains the only oral SERD to be approved, in second-line ER-positive, HER2-negative breast cancer, but it is only just entering phase 3 in adjuvant disease, well behind its SERD rivals. Roche, Lilly and AstraZeneca are all active here, with the Swiss group leading the pack. Roche is also ahead in the front line, with the Persevera study of its contender, giredestrant, set to read out next year. While Orserdu is approved for ESR1 mutants only, and other second-line failures have been put down to a focus on all-comers, Roche believes that in early lines it will be able to show a benefit regardless of ESR1 mutation status. The company has said that in early-stage disease tumours are still ER dependent, with ER activity comparable to that seen in second-line ESR1m patients. Still, Sanofi’s SERD amcenestrant flunked the first-line Ameera-5 trial in 2022, spurring that group to discontinue the whole programme, including an adjuvant study. Menarini has also so far made no move into first-line disease. The next big events for SERDs will be readout of two second-line phase 3 trials: Lilly’s Ember-3 and Arvinas/Pfizer’s Veritac-2. However, neither appears to be enriched for ESR1 mutants.

Oral SERDs in phase 3 development for adjuvant breast cancer

Note: All projects vs standard endocrine therapy; primary endpoint for all trials is invasive disease-free survival. Source: OncologyPipeline & clinicaltrials.gov.