Early progression on CDK4/6 regimen a ‘strong’ predictor of OS in breast cancer subset
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Key takeaways:
- The addition of fulvestrant or letrozole to palbociclib conferred similar efficacy.
- Progression during the first year of a CDK4/6 inhibitor-based regimen may be prognostic of less favorable outcomes.
SAN ANTONIO — The addition of either fulvestrant or letrozole to palbociclib conferred similar efficacy among patients with HER2-negative advanced breast cancer, according to data presented at San Antonio Breast Cancer Symposium.
Early disease progression within a year of initial treatment served as a predictor of shorter OS, results showed.
“Extended follow-up confirmed no differences between letrozole and fulvestrant when combined with palbociclib,” Antonio Llombart-Cussac, MD, PhD, chair of medical oncology at University Hospital Arnau de Vilanova in Spain, said during a presentation. “Results appeared consistent with data presented for other CDK4/6 inhibitors.”
Background and methods
The prospective phase 2 PARSIFAL study evaluated fulvestrant and letrozole as potential preferred endocrine partners for the CDK4/6 inhibitor palbociclib (Ibrance, Pfizer) for patients with untreated, endocrine-sensitive, hormone receptor-positive/HER2-negative advanced breast cancer.
Researchers randomly assigned patients 1:1 to palbociclib dosed at 125 mg daily in a 3-weeks-on, 1-week-off schedule for 28-day cycles plus either fulvestrant or letrozole.
Results showed no significant difference in PFS with letrozole or fulvestrant.
In the subsequent PARSIFAL-LONG study, researchers evaluated whether longer follow-up would show an OS benefit with either endocrine therapy. Secondary objectives included PFS, other post-progression efficacy outcomes, and the identification of potentially new prognostic and predictive markers.
The analysis included 389 patients, who accounted for 80.5% of the PARSIFAL study cohort.
Results and next steps
At median follow-up of 5 years (range, 0.1-7.3), researchers reported 241 PFS events and 213 OS events.
Researchers reported median PFS of 33.2 months (95% CI, 27.7-39.5) and median OS of 65.4 months (95% CI, 57.8-72).
Results showed no difference in PFS (HR = 1) or OS (HR = 0.94) between the fulvestrant and letrozole groups.
Among patients evaluated in PARSIFAL-LONG, 86 (22.1%) had median PFS shorter than 1 year, a group researchers characterized as “early progressors.”
In the early progressors subgroup, researchers reported median PFS of 7 months (95% CI, 5.6-8.3) and median OS of 24 months (95% CI, 17.3-30.1).
The other 303 patients in the long-term follow-up analysis remained progression free at 1 year. Among this group, researchers reported median PFS of 49.8 months (95% CI, 40.9-59.8) and median OS of 81.5 months (95% CI, 70.2 to not reached).
Achieving 12-month PFS appeared to be a strong predictor for median OS compared with early progressors (median, 27 months vs. 18 months; HR = 0.67; 95% CI, 0.51-0.9). It is possible the difference may widen moving forward, given 54.5% of patients who achieved 12-month PFS remained alive at data cutoff vs. 12.8% of early progressors.
“Early progression — less than 12 months — on a CDK4/6 inhibitor regimen is a strong clinical marker of a less favorable outcome,” Llombart-Cussac said.
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Llombart-Cussac J, et al. Abstract RF01-03. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2023; San Antonio.
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