Messaggi chiave
- PACE è uno studio randomizzato, multicentrico, di fase 2, che ha valutato il beneficio della prosecuzione del trattamento con CDK4/6 inibitori in associazione a endocrinoterapia oltre l’iniziale progressione in pazienti con carcinoma mammario metastatico HR+/HER2-.
- 220 pazienti sono state assegnate in rapporto 1:2:1 a fulvestrant (F), fulvestrant + palbociclib (F + P) o fulvestrant + palbociclib e avelumab (F + P + A). L’endpoint primario era la sopravvivenza libera da progressione (PFS) nel gruppo F rispetto a F + P.
- Dallo studio non è emerso alcun beneficio dall’aggiunta di palbociclib all’ormonoterapia (PFS mediana: 4,6 vs 4,8 mesi; p = 0,62), mentre è stato riscontrato un miglioramento non significativo degli esiti di sopravvivenza nel gruppo F + P + A rispetto a F (PFS mediana: 8,1 vs 4,8 mesi; p = 0,23), più accentuato nelle pazienti con alterazioni basali di ESR1 e PIK3CA e considerato dagli autori meritevole di ulteriori approfondimenti.
Abstract
Purpose
- Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting.
Methods
- The randomized multicenter phase II PACE trial enrolled patients with hormone receptor-positive/HER2- MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy.
- Patients were randomly assigned 1:2:1 to receive fulvestrant (F), fulvestrant plus palbociclib (F + P), or fulvestrant plus palbociclib and avelumab (F + P + A).
- The primary end point was investigator-assessed progression-free survival (PFS) in patients treated with F versus F + P.
Results
- Overall, 220 patients were randomly assigned between September 2017 and February 2022. The median age was 57 years (range, 25-83 years).
- Most patients were postmenopausal (80.9%), and 40% were originally diagnosed with de novo MBC.
- Palbociclib was the most common previous CDK4/6i (90.9%). The median PFS was 4.8 months on F and 4.6 months on F + P (hazard ratio [HR], 1.11 [90% CI, 0.79 to 1.55]; P = 0.62).
- The median PFS on F + P + A was 8.1 months (HR v F, 0.75 [90% CI, 0.50 to 1.12]; P = 0.23).
- The difference in PFS with F + P and F + P + A versus F was greater among patients with baseline ESR1 and PIK3CA alterations.
Conclusion
- The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor-positive/HER2- MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.
Note: Funded by Dana-Farber Cancer Institute; PACE ClinicalTrials.gov number, NCT03147287