Optimizing the clinical management of EGFR-mutant advanced non-small cell lung cancer: a literature review

BACKGROUND AND OBJECTIVE: Despite several steps forward in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), however there are still pending issues and upcoming challenges requiring adequate addressing in order to optimize the clinical management of metastatic patients harboring molecular alterations within the EGFR gene. This review aims to summarize the most recent findings regarding the diagnostic testing and therapeutic strategies of EGFR-mutant advanced NSCLC. METHODS: Literature search was conducted using MEDLINE/PubMed, EMBASE, Scopus and Cochrane Library databases, up to December 2021. Relevant studies in English language published between 2004 and 2021 were selected. KEY CONTENT AND FINDINGS: The increased detection of uncommon EGFR mutations in the real-word practice along with the clinical development of novel selective inhibitors, highlighted the issue of an adequate selection of the best EGFR-tyrosine-kinase inhibitor (TKI) to the right patient mutation. The advent of osimertinib in first-line has dramatically changed the spectrum of molecular mechanisms underlying both innate and acquired resistance to the EGFR-TKI therapy, accelerating the clinical investigation of novel genomic-driven sequential strategies as well as upfront targeted combinations. The recent approval of potent, selective inhibitors targeting the EGFR exon-20 insertions, renewed interest toward this patients’ subset, questioning the diagnostic accuracy of old-standard genomic sequencing technologies and pushing the implementations of next-generation sequencing (NGS)-based molecular profiling in the real word practice scenario. CONCLUSIONS: This review provides evidence-based answers to the aforementioned challenges aiming to optimize the clinical management of metastatic patients harboring molecular alterations within the EGFR gene

Adjuvant chemotherapy for resected triple negative breast cancer patients: A network meta-analysis

The current standard of care for resected early-stage triple negative breast cancer (TNBC) patients who did not receive systemic preoperative therapy is adjuvant anthracycline- and taxane-based chemotherapy (CT). A network meta-analysis (NMA) of randomized controlled trials (phase III) enrolling patients with resected stage I-III TNBC comparing adjuvant regimens was performed. Overall survival (OS) and disease-free survival (DFS) data were extracted. A total of 27 phase III clinical trials were selected including 15,242 TNBC patients. This NMA showed an OS benefit from the incorporation of capecitabine into classic anthracycline/taxane-based combinations compared to anthracyclines with or without taxanes alone

Retrospective study testing next generation sequencing of selected cancer-associated genes in resected prostate cancer

PURPOSE: Prostate cancer (PCa) has a highly heterogeneous outcome. Beyond Gleason Score, Prostate Serum Antigen and tumor stage, nowadays there are no biological prognostic factors to discriminate between indolent and aggressive tumors. The most common known genomic alterations are the TMPRSS-ETS translocation and mutations in the PI3K, MAPK pathways and in p53, RB and c-MYC genes. The aim of this retrospective study was to identify by next generation sequencing the most frequent genetic variations (GVs) in localized and locally advanced PCa underwent prostatectomy and to investigate their correlation with clinical-pathological variables and disease progression. RESULTS: Identified non-synonymous GVs included TP53 p.P72R (78% of tumors), two CSFR1 SNPs, rs2066934 and rs2066933 (70%), KDR p.Q472H (67%), KIT p.M541L (28%), PIK3CA p.I391M (19%), MET p.V378I (10%) and FGFR3 p.F384L/p.F386L (8%). TP53 p.P72R, MET p.V378I and CSFR1 SNPs were significantly associated with the HI risk group, TP53 and MET variations with T≥T2c. FGFR3 p.F384L/p.F386L was correlated with T≤T2b. MET p.V378I mutation, detected in 20% of HI risk patients, was associated with early biochemical recurrence. EXPERIMENTAL DESIGN: Nucleic acids were obtained from tissue samples of 30 high (HI) and 30 low-intermediate (LM) risk patients, according to D'Amico criteria. Genomic DNA was explored with the Ion_AmpliSeq_Cancer_Hotspot_Panel_v.2 including 50 cancer-associated genes. GVs with allelic frequency (AF) ≥10%, affecting protein function or previously associated with cancer, were correlated with clinical-pathological variables. CONCLUSION: Our results confirm a complex mutational profile in PCa, supporting the involvement of TP53, MET, FGFR3, CSF1R GVs in tumor progression and aggressiveness