Dr Sammons on the SONIA Trial of First-Line CDK4/6 Inhibitor Use in HR+/HER2– Breast Cancer

Sarah Sammons, MD, associate director, Metastatic Breast Cancer Program, Dana-Farber Cancer Institute, discusses whether CDK4/6 inhibitors should be considered a standard first-line treatment within hormone receptor (HR)–positive, HER2-negative advanced breast cancer according to primary results from the phase 3 SONIA trial (NCT03425838).

The investigator-initiated, randomized study was designed to evaluate the efficacy, safety, and cost-effectiveness of first- or second-line CDK4/6 inhibition in this population. The trial challenged the current trend of moving effective treatments like CDK4/6 inhibitors to earlier lines for the general patient population, and aimed to better inform the optimal sequencing of these agents, specifically palbociclib (Ibrance), Sammons begins.

Patients were randomly assigned 1:1 to receive a nonsteroidal aromatase inhibitor (AI) plus a CDK4/6 inhibitor or a nonsteroidal AI alone, Sammons details. Individuals who progressed on the CDK4/6 regimen went on to receive fulvestrant (Faslodex). Conversely, those who progressed on an AI alone went on to receive both fulvestrant and a CDK4/6 inhibitor, she states. Patients in the experimental arm were treated with either palbociclib, abemaciclib (Verzenio), or ribociclib (Kisqali) according to physician's choice. The majority of patients were treated with palbociclib, Sammons notes.

Results showed that use of CDK4/6 inhibitor plus endocrine therapy in the first-line setting did not significantly prolong time to progression on second-line therapy (PFS2) or overall survival (OS) compared with the regimen's employment in the second-line, Sammons reports. However, a progression-free survival (PFS) advantage was observed with first-line administration of the combination, with median PFS increasing by 16.5 months, she says.

Notably, patients who received a first-line CDK4/6 inhibitor had a median OS of 45.9 months vs 53.7 months with second-line CDK4/6 inhibitor treatment, Sammons adds. This is substantially lower than the median OS produced by first-line ribociclib or abemaciclib, she states.

Although these results were not practice changing, they indicate that first-line palbociclib is not superior to second-line use, Sammons explains. Accordingly, patients with toxicity concerns may consider starting with an AI alone before proceeding to second-line CDK4/6 inhibitor treatment, Sammons concludes.

Disclosures: Dr Sammons reports research funding from AstraZeneca, AbbVie, Bristol Myers Squibb, Eli Lilly, Seagen, and Sermonix; and consulting roles with Foundation Medicine, AstraZeneca, Daiichi Sankyo, Eli Lilly, Incyclix Bio, Merck, Pfizer, Seagen, Sermonix, and Novartis.