Atezolizumab plus bevacizumab as first-line treatment of unresectable hepatocellular carcinoma: interim analysis results from the phase IIIb AMETHISTA trial.

Background: The treatment of advanced hepatocellular carcinoma (HCC) with atezolizumab and bevacizumab led to significant improvements in overall survival (OS), progression-free survival (PFS), and response rate compared with sorafenib in the phase III IMbrave150 trial. The etiology of background liver disease can differ between Eastern and Western populations, leading to a potentially different impact of systemic therapies; therefore the unequal representation must be considered in the IMbrave150 trial. To provide further data on the safety and effectiveness of atezolizumab and bevacizumab, the phase IIIb AMETHISTA (Atezolizumab plus bevacizumab in METastatic HCC Italian Safety TriAl) ran in a Western (Italian) population of patients with advanced HCC.

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

Impact of Treatment With Trifluridine/Tipiracil in Combination With Bevacizumab on Health-Related Quality of Life and Performance Status in Refractory Metastatic Colorectal Cancer: An Analysis of the Phase III SUNLIGHT Trial.

Background: The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared to FTD/TPI for treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. This analysis of SUNLIGHT investigated the impact of treatment with FTD/TPI + bevacizumab on patient quality of life (QoL) and Eastern Cooperative Oncology Group performance status (ECOG PS).

Methods: Questionnaires (EORTC QLQ-C30 and EQ-5D-5L) and ECOG PS assessments were conducted at baseline and on Day 1 of each treatment cycle.

Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients.

Background: The Hormonal Bone Effects (HOBOE) study tested whether adjuvant triptorelin plus either letrozole (L) or zoledronic acid (Z) plus L (ZL) was more effective than tamoxifen (T) in premenopausal patients with hormone receptor-positive (HR+) early breast cancer (BC). Here we report the long-term follow-up analysis.

Patients And Methods: HOBOE (ClinicalTrials.

Paclitaxel for second-line treatment of squamous cell carcinoma of the head and neck: A multicenter retrospective Italian study.

Background: Squamous cell carcinoma of the head and neck (SCCHN) accounts for 3% of all malignant tumors in Italy. Immune checkpoint inhibitors combined with chemotherapy is first-line treatment for SCCHN; however, second-line treatment options are limited. Taxanes are widely used for combination therapy of SCCHN, as clinical trials have shown their efficacy in patients with this disease, particularly in patients with prior therapy.

Discovery of -substituted-2-oxoindolin benzoylhydrazines as c-MET/SMO modulators in EGFRi-resistant non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), the leading cause of cancer-related mortality worldwide, poses a formidable challenge due to its heterogeneity and the emergence of resistance to targeted therapies. While initially effective, first- and third-generation EGFR-tyrosine kinase inhibitors (TKIs) often fail to control disease progression, leaving patients with limited treatment options. To address this unmet medical need, we explored the therapeutic potential of multitargeting agents that simultaneously inhibit two key signalling pathways, the mesenchymal-epithelial transition factor (c-MET) and the G protein-coupled receptor Smoothened (SMO), frequently dysregulated in NSCLC.

Neoadjuvant Immunotherapy in Head and Neck Cancers: A Paradigm Shift in Treatment Approach.

Checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in the treatment of numerous solid tumors, including head and neck cancer. Their inclusion in the therapeutic paradigm in metastatic lines of treatment has certainly improved the outcomes of these patients. Starting from this assumption, numerous studies have been conducted on ICIs in other earlier disease settings, including studies conducted in patients in neoadjuvant settings.

Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial.

The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. A greater understanding of biomarkers predictive of response to Enco+Cetux±Bini treatment is of clinical relevance. In this prespecified, exploratory biomarker analysis of the BEACON CRC study, we characterize genomic and transcriptomic correlates of clinical outcomes and acquired resistance mechanisms through integrated clinical and molecular analysis, including whole-exome and -transcriptome tissue sequencing and circulating tumor DNA genomic profiling.

Comprehensive genomic profiling by liquid biopsy captures tumor heterogeneity and identifies cancer vulnerabilities in patients with RAS/BRAF wild-type metastatic colorectal cancer in the CAPRI 2-GOIM trial.

Background: Emerging evidence supports tumor tissue-based comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC). Data on liquid biopsy-based circulating tumor DNA (ctDNA) CGP are scarce and mainly retrospective. Prospective comparison between the two tests is not currently available.

Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma.

Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed.

Psychometric properties of patient-reported outcomes Common Terminology Criteria for adverse events (PRO-CTCAE®) in breast cancer patients: The prospective observational multicenter VIP study.

Patients' self-reporting is increasingly considered essential to measure quality-of-life and treatment-related side-effects. However, if multiple patient-reported instruments are used, redundancy may represent an overload for patients. Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) are a tool allowing direct patients' reporting of side-effects.

Inverse FASN and LDHA correlation drives metabolic resistance in breast cancer.

Background: Breast cancer manifests as a heterogeneous pathology marked by complex metabolic reprogramming essential to satisfy its energy demands. Oncogenic signals boost the metabolism, modifying fatty acid synthesis and glucose use from the onset to progression and therapy resistant-forms. However, the exact contribution of metabolic dependencies during tumor evolution remains unclear.

Temozolomide based treatment in glioblastoma: 6 vs. 12 months.

The Stupp regimen remains the standard treatment for newly diagnosed glioblastomas, although the prognosis remains poor. Several temozolomide alternative schedules have been studied, with extended adjuvant treatment (>6 cycles of temozolomide) frequently used, although different trials have indicated contrasting results. Survival data of 87 patients who received 6 ('6C' group) or 12 ('12C' group) cycles of temozolomide were collected between 2012 and 2022.

TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-β signaling plays a crucial role in various cellular processes, including growth, differentiation, apoptosis, epithelial-mesenchymal transition (EMT), regulation of the extracellular matrix, angiogenesis, and immune responses. TGF-β signals through SMAD proteins, which are intracellular molecules that transmit TGF-β signals from the cell membrane to the nucleus.

Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?

Colorectal carcinoma (CRC) with deficiency of the deficient mismatch repair (dMMR) pathway/microsatellite instability (MSI) is characterized by a high mutation load and infiltration of immune cells in the tumor microenvironment. In agreement with these findings, clinical trials have demonstrated a significant activity of immune checkpoint inhibitors (ICIs) in dMMR/MSI metastatic CRC (mCRC) patients and, more recently, in CRC patients with early disease undergoing neoadjuvant therapy. However, despite high response rates and durable clinical benefits, a fraction of mCRC patients, up to 30%, showed progressive disease when treated with single agent anti-programmed cell death 1 (PD-1) antibody.

Plain language summary of SUNLIGHT: trifluridine/tipiracil and bevacizumab for refractory metastatic colorectal cancer.

What Is This Summary About?: This is a summary describing the results from a phase 3 clinical trial called SUNLIGHT. The study looked at treatment with orally administered trifluridine/tipiracil plus intravenously administered bevacizumab in people with metastatic colorectal cancer (mCRC) that is refractory to treatment.This study included people whose cancer had grown or spread beyond its original location after no more than two previous treatments.

Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial.

Background: CAVE is a single arm, Phase 2 trial, that demonstrated anti-tumor activity of cetuximab rechallenge plus avelumab in patients with RAS wild type (wt) metastatic colorectal cancer (mCRC).

Objective: We conducted a post hoc analysis to identify potential radiomic biomarkers for patients with CRC liver metastasis (LM).

Patients And Methods: Patients with LM that could be measured by enhanced contrast phase computed tomography (CT) imaging at baseline and at first response evaluation were included.

Targeting the EGFR signalling pathway in metastatic colorectal cancer.

Epidermal growth factor receptor (EGFR) and its activated downstream signalling pathways play a crucial role in colorectal cancer development and progression. After four decades of preclinical, translational, and clinical research, it has been shown that blocking the EGFR signalling pathway at different molecular levels represents a fundamental therapeutic strategy for patients with metastatic colorectal cancer. Nevertheless, the efficacy of molecularly targeted therapies is inescapably limited by the insurgence of mechanisms of acquired cancer cell resistance.