A phase 3 trial of Roche’s giredestrant in first-line breast cancer patients has missed its primary endpoint, tarnishing the record of a drug that hit the mark in adjuvant and second-line settings.
Last year, Roche reported phase 3 victories for its oral selective estrogen receptor degrader (SERD) in a previously treated population of breast cancer patients and when used as an adjuvant in people with a certain form of early-stage breast cancer. TD Cowen analysts said in a note to investors in January that the adjuvant win could be interpreted as strongly suggesting first-line success for giredestrant.
Yet Roche reported Monday that progression-free survival (PFS) was statistically no better on giredestrant than on the active control regimen in the phase 3 persevERA trial. The study randomized people with ER-positive, HER2-negative, locally advanced or metastatic breast cancer to receive giredestrant or the aromatase inhibitor letrozole in combination with Pfizer’s CDK4/6 inhibitor Ibrance.
Roche said it saw a numerical improvement in PFS. Adverse events on giredestrant and Ibrance were manageable and consistent with the known safety profiles of each individual treatment, the pharma added.
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Despite the setback, Roche Chief Medical Officer Levi Garraway, M.D., Ph.D., said in a statement that the company is confident in the potential of giredestrant to become a standard-of-care endocrine therapy in early and advanced ER-positive breast cancer. Roche has filed for FDA approval based on the second-line trial and plans to submit the adjuvant data to the agency in the coming weeks.
The Swiss drugmaker continues to test giredestrant in another first-line setting. While the failed trial enrolled endocrine-sensitive patients, the ongoing pionERA is targeting patients with endocrine-resistant breast cancer. The company expects to release pionERA data next year.
Roche’s failure raises questions about the efficacy of oral SERDs in first-line patients. AstraZeneca hailed a first-line win for its oral SERD camizestrant one year ago, but the trial used a novel design that switched patients to the drug candidate if a mutation was detected before disease progression. Another phase 3 trial testing camizestrant plus Ibrance as a first-line treatment is scheduled to deliver data this year.
TD Cowen analysts said front-line metastatic success would add meaningfully to the opportunity open to oral SERDs. Before Roche’s phase 3 flop, the analysts forecast giredestrant sales would hit 5 billion Swiss francs ($6.4 billion) in 2030. The analysts forecast camizestrant sales of $2 billion in 2030.
