HRQOL the Same With CDK4/6 Inhibitors in 1st or 2nd Line

SAN ANTONIO — For patients with advanced hormone receptor-positive, HER2-negative breast cancer, health-related quality of life is the same whether they receive CDK4/6 inhibitors in the first or second line of therapy, according to investigators in the SONIA trial.

The health-related quality of life data come from a new analysis of a secondary endpoint of the phase 3 trial, reported in a scientific poster and oral poster spotlight session at the San Antonio Breast Cancer Symposium 2024.

As previously reported by Medscape Medical News, In the SONIA trial, 1050 patients were randomized to receive a CDK4/6 inhibitor of the treating physician’s choice in either the first or second line. The drugs were partnered with aromatase inhibitors when used in the first line and with fulvestrant (Faslodex) when used in the second line.

For the primary endpoint of progression-free survival (PFS) after the first line of therapy compared with PFS following the second line of therapy (PFS2), the investigators noted that they saw no significant difference in PFS with either treatment strategy. But they did see a significant increase in grade 3 or greater toxicities and increased costs when CDK4/6 inhibitors were given in the first line. 

The data suggests doctors should withhold giving CDK4/6 inhibitors until disease progression following first-line therapy, according to the authors.

QoL Analysis

At SABCS 2024, the SONIA investigators reported in a scientific poster the results of a secondary endpoint evaluating patient-reported health-related quality of life (HRQOL) of patients in the trial, as measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire.

The questionnaire was administered at baseline and at 12, 24, 48 and 72 weeks on both first- and second-line treatment, and at the time that patients discontinued treatment on trial.

The investigators, led by Noor Wortelboer, calculated both total FACT-B score and subscale scores for physical, social, emotional, and functional well-being, as well as the breast cancer subscale for all questionnaires completed within 2 months of treatment discontinuation. Wortelboer is a PhD candidate at Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands.

The researchers found that the differences between FACT-B total scores and subscale scores for patients treated with a CDK4/6 inhibitor in either the first or second line were close to zero at all time points.

“These data indicate that adding CDK4/6i in first-line compared to second-line does not result in improved HRQOL, providing further justification for deferring the use of CDK4/6i to second-line treatment,” the investigators wrote.

‘Incredibly Important’

“Overall health related quality of life is incredibly important for us to be looking at in metastatic breast cancer, especially as we’re seeing overall survival improved and prolonged durations on therapy, and SONIA indicates that there may be a population who could defer CDK4/6 inhibitors to the second line, with no compromise in PFS2 or health related quality of life,” commented Kari B. Wisinski, MD, professor of medicine at the University of Wisconsin Carbone Cancer Center, Wisconsin, in a poster spotlight session.

Wisinski, the invited discussant, said that some factors that may influence the quality of life results in SONIA include a fairly endocrine sensitive population, with 86% of patients being postmenopausal, and the fact that patients generally had favorable-risk disease, with either de novo breast cancer or a prolonged disease-free interval following adjuvant therapy. 

In addition, more than 90% of patients in the trial were prescribed palbociclib, which has a comparatively low toxicity profile, as evidenced by low rates of grade 3 or 4 adverse events, particularly in symptoms that may affect quality of life, and manageable grade 1 or 2 adverse events, she pointed out.

Regarding SONIA “it’s really unclear if these results are applicable beyond palbociclib, and we do have first-line data with ribociclib improving overall survival benefit, and abemaciclib having this clinically meaningful benefit. So, we really need to understand, does waiting to the second line with the CDK4/6 inhibitor continue to maintain that overall survival benefit?” Wisinski said.

The study was funded by the Dutch government and Dutch Health Insurers. Wortelboer reported no conflicts of interest. Wisinski disclosed consulting for Gilead, grant/research support from Pfizer and Novartis, honoraria from Loxo@Lilly, AstraZeneca, Gilead, and Stemline Therapeutics and contracted research for Pfizer, Novartis, Sanofi, Seagen, Jazz, AstraZeneca, Puma, Relay, and Genentech/Roche. 

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape Medical News.