Early progression on CDK4/6 regimen including palbociclib is 'strong' predictor of OS in breast cancer subgroup

Adding fulvestrant or letrozole to palbociclib treatment has similar efficacy in patients with HER2-negative advanced breast cancer, according to data published in one study. Results showed that early disease progression within one year of initial treatment was a predictor of shorter overall survival (OS). Long-term follow-up confirmed no difference between letrozole and fulvestrant when combined with palbociclib, and the results appear to be consistent with data from other CDK4/6 inhibitors.

Prospective The phase 2 PARSIFAL study evaluated fulvestrant and letrozole as potential first-choice endocrine partners of the CDK4/6 inhibitor palbociclib in patients with untreated, endocrine-sensitive, hormone receptor-positive/HER2-negative advanced breast cancer. The researchers randomly assigned patients in a 1:1 ratio to a daily dose of 125 mg of palbociclib, which was taken continuously for 3 weeks with a 1-week break in a 28-day cycle, along with fulvestrant or letrozole. The results showed no significant difference in progression-free survival (PFS) between letrozole or fulvestrant.

In the subsequentPARSIFAL-LONG study, researchers evaluated whether long-term follow-up would show an OS benefit from either endocrine therapy. Secondary objectives include PFS, other post-progression efficacy outcomes, and the identification of potential new prognostic and predictive markers. The analysis included 389 patients, representing 80.5% of the PARSIFAL study cohort. During a median follow-up of 5 years (range0.1-7.3), researchers reported 241 PFS events and 213 OS events. The median PFS was 33.2 months (95% CI, 27.7-39.5), and the median OS was 65.4 months (95% CI, 57.8-72). The results showed no difference in PFS (HR=1) or OS (HR=0.94) between the fulvestrant and letrozole groups.

Among the patients evaluated by PARSIFAL-LONG, 86 (22.1%) had a median PFS of less than 1 year, which one group of researchers termed "early progressors" In the early progression subgroup, researchers reported a median PFS of 7 months (95% CI, 5.6-8.3) and a 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. In this group of patients, the researchers reported a median PFS of 49.8 months (95% CI, 40.9-59.8) and a median OS of 81.5 months (95% CI, 70.2 to not reached).

Achieving PFS of 12 months appeared to be a strong predictor of median OS compared with early progressors (median, 27 months vs. 18 months; HR = 0.67; 95% CI, 0.51-0.9). This difference may widen further given that 54.5% of patients achieving 12-month PFS were still alive at data cutoff compared with 12.8% of early progressors.