Roche delivers its data reveal for adjuvant giredestrant

Roche has revealed the data that has it excited about oral SERD giredestrant in early-stage breast cancer, which could put the drug on course to add to the options for adjuvant therapy.

The results of the lidERA trial in patients with HR-positive, HER2-negative early breast cancer – previewed last month and revealed in full at the San Antonio Breast Cancer Symposium (SABCS) – show that giredestrant achieved a 30% reduction in invasive disease-free survival (iDFS) compared to standard-of-care endocrine therapy.

Roche said that giredestrant is the only oral SERD to achieve that in a phase 3, adjuvant setting trial, and represents "the first significant endocrine therapy advance in over 20 years" for patients with this type of breast cancer.

There was also a trend towards improved overall survival (OS) with giredestrant, with 92.4% of patients taking the oral SERD still alive at three years compared to 89.6% of the endocrine therapy group, but that data remains immature and has not reached statistical significance.

HR-positive breast cancer accounts for around 70% of breast cancer cases, added the company, and up to a third of patients see a recurrence on or after adjuvant endocrine therapy treatment.

The new result could allow Roche to position giredestrant in an earlier treatment setting than other drugs in the class. As it stands, there are two oral SERDs on the market – Menarini/Stemline's Orserdu (elacestrant) and Eli Lilly's Inluriyo (imlunestrant) – which are currently approved as second-line treatments for advanced HR+/HER2- breast cancer with ESR1 mutations, and in late-stage testing for adjuvant use.

It's noteworthy that lidERA started before two CDK4/6 inhibitors – Eli Lilly's Verzenio (abemaciclib) and Novartis' Kisqali (ribociclib) – have now been approved for adjuvant use in HR+/HER2- breast cancer and also outperformed endocrine therapy in their phase 3 trials.

$5 billion-a-year blockbuster Verzenio – currently approved for node-positive disease only – has already been shown to improve OS by a statistically significant 15.8% when added to endocrine therapy in the monarchE trial.

Meanwhile, Kisqali did not show a significant improvement in OS in the NATALEE trial, but has been growing fast, with sales reaching $3 billion last year, thanks to its approval in both node-positive and node-negative patients.

If approved, giredestrant's place in the adjuvant treatment will likely depend on multiple factors, including side effects – all three drugs have different safety profiles – and whether patients are considered high, intermediate, or low risk of recurrence, according to discussion of the results at SABCS.