Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer
Mené sur 106 patientes atteintes d'un cancer du sein ER+ HER2- à haut risque de récidive (durée médiane de suivi : 40,4 mois), cet essai de phase II évalue l'efficacité, du point de vue de la survie globale et de la survie spécifique, et la toxicité d'un traitement néoadjuvant combinant létrozole et palbociclib par rapport à une chimiothérapie de troisième génération
Background : Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, randomised phase 2 NEOPAL trial showed that the letrozole-palbociclib combination led to clinical and pathological responses equivalent to sequential anthracycline-taxanes chemotherapy. Secondary objectives included survival outcomes. Methods : Secondary end-points of NEOPAL included progression-free survival (PFS) and invasive-disease free survival (iDFS) in the intent-to-treat population. Exploratory end-points were overall survival (OS) and breast cancer specific survival (BCSS) in the intent-to-treat population, as well as iDFS, OS and BCSS according to the administration of chemotherapy. Results : Hundred and six patients were randomised. Pathological complete response rates were 3.8% and 5.9%. Twenty-three of the 53 patients in the letrozole-palbociclib arm received postoperative adjuvant chemotherapy. At a median follow-up of 40.4 months [0–56.6], 11 progressions have been observed, of which three were in the letrozole-palbociclib and 8 in the control arm. PFS (HR = 1.01; [95%CI 0.36–2.90], p = 0.98) and iDFS (HR = 0.83; [95%CI 0.31–2.23], p = 0.71) did not differ between both arms. The 40 months PFS rate was 86.7% [95%CI 78.0–96.4] and 89.9% [95%CI 81.8–98.7] in letrozole-palbociclib and control arms, respectively. Outcomes of patients who did not receive chemotherapy were not statistically different from those who received it. Conclusions : NEOPAL suggests that a neoadjuvant letrozole-palbociclib strategy may allow sparing chemotherapy in some patients with luminal breast cancer while allowing good long-term outcomes. Larger confirmatory studies are needed.