The lancet oncology
-
Over the past two decades, targeted therapies have become cornerstone treatments for numerous cancers with oncogene addiction. Unfortunately, their effectiveness reduces over time and most patients who receive targeted therapies relapse within 12 months. The emergence of drug-resistance mechanisms in tumours paved the way for next-generation inhibitors. ⋯ This scenario has led us to propose a new concept in clinical drug development: the late phase 1 study. The primary goal of this type of trial is to define an alternative MTD of a drug in patients who are chronically exposed and had an initial benefit from targeted therapy but subsequently progressed without an identified resistance alteration. Intrapatient dose escalation might increase drug concentration and restore drug activity or efficacy.
-
The lancet oncology · Oct 2021
Randomized Controlled Trial Multicenter StudyExtended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial.
The benefit of extending aromatase inhibitor therapy beyond 5 years in the context of previous aromatase inhibitors remains controversial. We aimed to compare extended therapy with letrozole for 5 years versus the standard duration of 2-3 years of letrozole in postmenopausal patients with breast cancer who have already received 2-3 years of tamoxifen. ⋯ For the Italian translation of the abstract see Supplementary Materials section.