Concurrent or sequential letrozole with adjuvant breast radiotherapy: Final results of the CO-HO-RT phase II randomized trial
Mené sur 150 patientes ménopausées atteintes d'un cancer du sein de stade I à II (durée médiane de suivi : 74 mois), cet essai de phase II évalue, en fonction du schéma thérapeutique, la toxicité du létrozole en combinaison avec une radiothérapie adjuvante
Background : We present here final clinical results of the COHORT trial and both translational sub-studies aiming at identifying patients at risk of radiation-induced subcutaneous fibrosis (RISF): (i) radiation-induced lymphocyte apoptosis (RILA) and (ii) candidates of certain single nucleotide polymorphisms (SNP). Patients and methods : Postmenopausal patients with stage I–II breast cancer (n=150) were enrolled and assigned to either concurrent (arm A) or sequential radiotherapy-letrozole (arm B). Among them, 121 were eligible for RILA and SNP assays. Grade ≥2 RISF were the primary endpoint. Secondary endpoints were lung and heart events and carcinologic outcome. RILA was performed to predict differences in RISF between individuals. A genome-wide association study was performed to identify SNPs associated with RILA and RISF. Analyses were done by intention to treat. Results : After a median follow-up of 74 months, 5 patients developed a grade ≥2 RISF. No significant difference was observed between arms A and B. Neither grade ≥2 lung nor symptomatic cardiac toxicity was observed. Median RILA value of the five patients who had grade ≥2 RISF was significantly lower compared to those who developed grade ≤1 RISF (6.9% vs 13%, p=0.02). Two SNPs were identified as being significantly associated with RILA: rs1182531 (p=4.2x10−9) and rs1182532 (p=3.6x10−8); both located within the PHACTR3 gene on chromosome 20q13.33. Conclusions : With long-term follow-up, letrozole can safely be delivered concomitantly with adjuvant breast radiotherapy. Translational sub-studies showed that high RILA values were correlated with patients who did not develop RISF.