SABCS 2025 – Roche mounts its early breast cancer challenge

Roche’s oral SERD giredestrant has shown a statistically significant and clinically meaningful benefit in adjuvant breast cancer, with a 30% reduction in the likelihood of a patient developing invasive disease versus standard of care.

The results from the Lidera trial, presented on Wednesday at the San Antonio Breast Cancer Symposium, led to the investigators heralding the project as a “potentially new standard” in adjuvant ER-positive, HER2-negative breast cancer.

However, Lidera compared giredestrant against physician’s choice of endocrine therapy, such as Tamoxifen or Femara, rather than versus more recently approved CDK4/6 inhibitors like Novartis’s Kisqali or Lilly’s Verzenio.

Source: Dr Aditya Bardia & SABCS.

Presenting the results at a SABCS press briefing, UCLA’s Dr Aditya Bardia noted that Lidera began before CDK4/6 inhibitors were approved for adjuvant disease.

On a cross-trial basis giredestrant looks similar to the CDK4/6 inhibitors: the MonarchE trial of Verzenio and the Natalee study of Kisqali reported 35% and 25% respective reductions in risk of an iDFS event when these agents were combined with endocrine therapy, versus endocrine therapy alone.

Still, the trials aren't completely comparable. Lidera enrolled patients with stage I-III disease, while MonarchE and Natalee focused on stage II and III disease. Stage I is the earliest, so this might have worked in favour of giredestrant. Meanwhile, both Lidera and MonarchE homed in on node-positive patients, while Natalee included both node-positive and negative disease.

Decisions

Assuming that giredestrant goes on to be approved here, Bardia said the decision about which drug to use could come down to a tradeoff between efficacy and toxicity. 

The most common side effects with giredestrant were arthralgia and asymptomatic bradycardia, while he called out liver enzyme increases and QTc prolongation with Kisqali, and diarrhoea and myelosuppression with Verzenio.

One disadvantage for Roche might be a lack of a statistically significant survival benefit. Lidera showed a trend towards an improvement in OS, with a hazard ratio of 0.79, but the data are only 31% mature, and the trial will continue to analyse OS.

Source: Dr Aditya Bardia & SABCS.

Lilly reported an OS win at this year’s ESMO meeting with Verzenio in MonarchE; at the last analysis, OS data from Kisqali’s Natalee trial were immature, with a hazard ratio of 0.80.

Verzenio was FDA approved for node-positive, high-risk early breast cancer in 2021; Kisqali’s 2024 nod also covered node-negative disease.

The Lidera trial also includes a substudy testing giredestrant plus Verzenio, but data from this portion aren’t yet available.

Other oral SERD developers are also taking aim at early breast cancer, with AstraZeneca’s camizestrant being tested in the Cambria-1 and 2 trials, Lilly’s Inluriyo in the Ember-4 study, and Menarini’s Ordserdu in the Elegant trial.

Giredestrant also recently prevailed in second-line breast cancer, with an FDA filing expected next year. The next big readout for the project will be from the first-line Persevera trial, delayed from 2025 to 2026.

Cross-trial comparison in adjuvant ER-positive, HER2-negative breast cancer

Notes: *data cutoff 8 Aug 2025; AI=aromatase inhibitor; iDFS=invasive disease-free survival. Source: SABCS 2025 & product labels.