Paolo Sala

Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer

Introduction Patients with high-grade serous ovarian cancer (HGSOC) have a poor prognosis, and current chemotherapy regimens for treating advanced disease are far from satisfactory. Prexasertib (LY2606368) is a novel checkpoint kinase inhibitor (CHK) under investigation for the treatment of HGSOC. Data from a recent phase II trial showed promising efficacy and safety results for treating wild-type BRCA HGSOC. Areas covered This article reviews the available data on the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of prexasertib in the treatment of HGSOC. Expert opinion Until now, prexasertib demonstrated clinical activity in phase I and II clinical trial for treating wild-type BRCA HGSOC, whereas its promising efficacy as monotherapy and combined with olaparib in BRCA-mutated HGSOC has been preliminary evidenced only in phase I studies. Compared to other drugs of the same class, prexasertib showed a better tolerability profile, causing moderate hematological toxicity. Further studies are needed to confirm efficacy and safety profiles of prexasertib in combined regimens. New early clinical trials may investigate prexasertib administered with programmed cell death ligand 1 (PD-L1) and PI3 K inhibitors due to the preclinical evidence of a synergic action.

Neoadjuvant Chemotherapy Followed by Radical Surgery versus Concurrent Chemo-Radiotherapy in the Treatment of Locally Advanced Cervical Cancer: A Multicenter Retrospective Analysis

This study aims to evaluate oncological outcomes in women affected by locally advanced cervical cancer (LACC) treated by neoadjuvant chemotherapy before radical surgery (NACT + RS) or concurrent chemo-radiotherapy (CCRT). This was a multicenter retrospective analysis of data related to women with LACC (FIGO stage IB2-IVA), who were treated by NACT + RS or CCRT between November 2006 and January 2018. The first endpoints were the evaluation of disease-free survival (DFS) and overall survival (OS); univariate and multivariate analyses were performed for identifying the prognostic factors independently associated with these oncological outcomes. Overall, 106 women were included in the analysis; 55 of them (51.9%) underwent NACT + RS and 51 (48.1%) CCRT, respectively. Patients in the NACT + RS group had a significant better five-year DFS and five-year OS than those in the CCRT group (77.4% vs. 33.4%, This retrospective study demonstrated an improved survival outcome for patients undergoing NACT + RS compared with those undergoing CCRT. Our findings seem to support the use of NACT before RS as an effective alternative option to CCRT standard therapy.