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Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Intermittent androgen deprivation therapy (ADT) involves cycling ADT, allowing hormonal recovery during off-treatment periods. This could lead to a better quality of life during off-treatment periods and could delay progression to castration resistance. Safety and feasibility of intermittent ADT have been shown but tolerability and health-related quality of life improvement have been suggested but questioned by others. Results from randomized trials, including relapsing or mixed populations, have suggested intermittent ADT to be as effective as continuous ADT. In this study of only metastatic patients, no statistical difference in either overall survival or progression-free survival was shown between intermittent and continuous ADT and suggests that intermittent might be as safe as continuous castration. It could be an option in highly responding and well-informed metastatic patients even if no clear benefit in health-related quality of life was shown. This intermittent modality could be of interest in metastatic patients with significant treatment-induced side-effects. OBJECTIVE To compare intermittent androgen deprivation therapy (ADT) and continuous ADT after 6 months of induction of ADT in patients with metastatic prostate cancer (PCa)., PATIENTS AND METHODS This is an open-label randomized multi-centre study conducted in 58 centres in Europe., Patients with metastatic PCa and prostate-specific antigen (PSA) level >20 ng/mL at selection were randomized after 6 months of induction of ADT (leuprorelin and flutamide) if PSA level had decreased below 4 ng/mL., Patients received either continuous or intermittent ADT. All patients were treated until signs of disease progression under treatment or until study end with a monthly central PSA determination and follow-up visits were performed every 3 months., The primary endpoint was overall survival. Secondary endpoints included progression-free survival, health-related quality of life (QLQ C30 questionnaire) and safety criteria., RESULTS Of 383 selected patients, 173 had a PSA level below 4 ng/mL after 6 months of induction of ADT and were randomized. Median overall survival (52 vs 42 months, P= 0.75) and median progression-free survival (15.1 vs 20.7 months, P= 0.74) were not significantly different between continuous and intermittent ADT., Although some differences in quality of life were observed, most of the functional and symptom scales showed no significant difference between the two groups., Significantly fewer treatment-emergent adverse events occurred in the intermittent group ( P= 0.042), with the incidence of headache and hot flushes also lower., CONCLUSIONS This first randomized trial comparing continuous with intermittent ADT in metastatic PCa suggests that intermittent ADT might be as safe as continuous ADT., It could be an option in highly responding and well-informed patients even if no clear benefit in health-related quality of life was shown. [ABSTRACT FROM AUTHOR]

Introduction Lung cancer kills approximately 1 million people every year worldwide and is the leading cause of death by cancer in the world. Lung cancer consists of 2 main types: [...], EGFR-mutated lung adenocarcinoma patients treated with gefitinib and osimertinib show a therapeutic benefit limited by the appearance of secondary mutations, such as [EGFR.sup.T790M] and [EGFR.sup.C7975]. It is generally assumed that these secondary mutations render EGFR completely unresponsive to the inhibitors, but contrary to this, we uncovered here that gefitinib and osimertinib increased STAT3 phosphorylation (p-STAT3) in [EGFR.sup.T790M] and [EGFR.sup.C7975] tumoral cells. Interestingly, we also found that concomitant Notch inhibition with gefitinib or osimertinib treatment induced a p-STAT3-dependent strong reduction in the levels of the transcriptional repressor HES1. Importantly, we showed that tyrosine kinase inhibitor-resistant tumors, with [EGFR.sup.T790M] and [EGFR.sup.C7975] mutations, were highly responsive to the combined treatment of Notch inhibitors with gefitinib or osimertinib, respectively. Finally, in patients with EGFR mutations treated with tyrosine kinase inhibitors, HES1 protein levels increased during relapse and correlated with shorter progression-free survival. Therefore, our results offer a proof of concept for an alternative treatment to chemotherapy in lung adenocarcinoma osimertinib- treated patients after disease progression.