Determinants of activity and efficacy of anti-PD1/PD-L1 therapy in patients with advanced solid tumors recruited in a clinical trials unit: a longitudinal prospective biomarker-based study.

Immune-checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of cancer. However, optimal patient selection is still an unmet need. One-hundred-forty-six patients with metastatic cancer candidates to ICI at the Hospital Clinic of Barcelona Clinical Trials Unit were prospectively recruited in this observational study.

Glutamine and Cholesterol Plasma Levels and Clinical Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Taxanes.

Altered metabolism is a hallmark of cancer. Malignant cells metabolise glutamine to fulfil their metabolic needs. In prostate cancer, androgen receptor signalling promotes glutamine metabolism, which is also involved in cholesterol homeostasis.

Encephalitis Associated With Immune Checkpoint Inhibitor Treatment in Patients With Melanoma.

Since the approval of immune checkpoint anti-programmed cell death protein 1 antibodies (pembrolizumab and nivolumab) and anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) in combination or monotherapy, significant advances have been made in the treatment of metastatic melanoma. The nonspecific immune stimulation resulting from these drugs can case a wide range of side effects in many organs including the nervous system, named immune-related adverse events. Few immune-related encephalitis associated with these antibodies have been described in the literature.

Molecular characterization of advanced non-small cell lung cancer patients by cfDNA analysis: experience from routine laboratory practice.

Background: Analysis of circulating free DNA (cfDNA) by the real-time PCR cobas EGFR Mutation Test v2 (cobas EGFR Test) is a diagnostic approach used in clinical practice for the characterization of advanced non-small cell lung cancer (NSCLC) patients. The test additionally outputs a semiquantitative index (SQI) which reflects the proportion of mutated versus wild-type copies of the gene in cfDNA with potential use as a biomarker. CfDNA concentration and cfDNA fragmentation pattern have also shown potential utility as biomarkers for cancer patients.

A first-in-human phase I/Ib dose-escalation clinical trial of the autophagy inducer ABTL0812 in patients with advanced solid tumours.

Background: ABTL0812 is an autophagy inducer that promotes cancer cell death by activation of cytotoxic autophagy selectively in tumour cells. ABTL0812 induces endoplasmic reticulum stress and blocks the Akt-mTOR axis; both actions converge to activate a robust and sustained autophagy leading to cancer cell death. Preclinical data supported the initiation of clinical trials in patients with cancer.

Cell Plasticity-Related Phenotypes and Taxanes Resistance in Castration-Resistant Prostate Cancer.

The prostatic tumor cells plasticity is involved in resistance to hormone-therapy, allowing these cells to survive despite androgen receptor inhibition. However, its role in taxanes resistance has not been fully established. Gene expression of plasticity-related phenotypes such as epithelial-mesenchymal transition (EMT), stem cell-like and neuroendocrine (NE) phenotypes was studied , , in circulating tumor cells (CTCs) (=22) and in tumor samples (=117) from taxanes-treated metastatic castration-resistant prostate cancer (mCRPC) patients.

Androgen Receptor and Its Splicing Variant 7 Expression in Peripheral Blood Mononuclear Cells and in Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer.

Androgen receptor (AR) signaling remains crucial in castration-resistant prostate cancer (CRPC). Since it is also essential in immune cells, we studied whether the expression of AR full-length and its splicing variant in peripheral blood mononuclear cells (PBMC) predicts systemic treatment response in mCRPC in comparison with circulating-tumor cells (CTC). We measured and mRNA in PBMC and CTC from patients prior to receiving abiraterone (AA), enzalutamide (E), or taxanes by a pre-amplification plus quantitative reverse-transcription PCR.

The influence of treatment sequence in the prognostic value of TMPRSS2-ERG as biomarker of taxane resistance in castration-resistant prostate cancer.

TMPRSS2-ERG expression in blood has been correlated with low docetaxel benefit in metastatic castration-resistant prostate cancer (mCRPC). This multicenter study aimed to prospectively asses its role as a taxane-resistance biomarker in blood and retrospectively in tumors, exploring also the impact of prior abiraterone/enzalutamide (A/E) in patients and in vitro. TMPRSS2-ERG was tested by quantitative reverse-transcription PCR.

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study.

Objectives: In the EXTREME trial, a combination of cisplatin or carboplatin plus 5-fluorouracil (5-FU) and cetuximab was superior to cisplatin/carboplatin plus 5-FU for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). With the aim of improving fluoropyrimidine-related tolerance without decreasing its efficacy, the safety and efficacy of carboplatin plus the oral fluoropyrimidine tegafur and cetuximab were investigated.

Methods: A retrospective analysis of 104 patients with recurrent or metastatic HNSCC was conducted.

Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer.

Background: Although chemotherapy is the cornerstone treatment for patients with metastatic colorectal cancer (mCRC), acquired chemoresistance is common and constitutes the main reason for treatment failure. Monoclonal antibodies against insulin-like growth factor-1 receptor (IGF-1R) have been tested in pre-treated mCRC patients, but results have been largely deceiving.

Methods: We analysed time to progression, overall survival, and the mutational status of RAS, BRAF and nuclear p-IGF-1R expression by immunohistochemistry, in 470 metastatic CRC patients.

Immune-Related Gene Expression Profiling After PD-1 Blockade in Non-Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma.

Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor specimens from 65 patients with melanoma, lung nonsquamous, squamous cell lung or head and neck cancers who were treated with the approved PD1-targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS).

Motor polyradiculopathy during pembrolizumab treatment of metastatic melanoma.

Introduction: Pembrolizumab, a monoclonal antibody directed against the immune checkpoint programmed cell death-1 receptor (PD-1), has improved survival in patients with advanced melanoma. Neuromuscular immune-mediated side effects have been rarely reported.

Methods: We describe a 44-year-old man with metastatic melanoma who presented with progressive muscle weakness after 23 doses of pembrolizumab.

Life-threatening colitis and complete response with ipilimumab in a patient with metastatic BRAF-mutant melanoma and rheumatoid arthritis.

Immune checkpoint inhibitors, such as ipilimumab (an anti-CTLA4 antibody), have become a commonly used therapy in cancer. To date, safety data of patients with underlying autoimmune disease is limited. We present a case of a patient with rheumatoid arthritis who was diagnosed of a BRAF-mutant metastatic melanoma.

Ipilimumab after progression on anti-PD-1 treatment in advanced melanoma.

Aim: While both efficacy and safety of anti-PD-1 agents seem to be independent of previous treatment with anti-CTLA-4, limited data exist of efficacy and toxicity of ipilimumab after progression on anti-PD-1 therapy. This retrospective analysis describes the efficacy and safety of sequential therapy with ipilimumab in patients with metastatic melanoma who progressed on anti-PD-1 antibody.

Methods: Nine patients who progressed on anti-PD-1 therapy received four cycles of ipilimumab 3 mg/kg every 3 weeks.

Pembrolizumab in a BRAF-mutant metastatic melanoma patient following a severe immune-related adverse event with ipilimumab.

Currently, limited data exist on the safety of pembrolizumab in patients with metastatic melanoma who have developed severe immune-related adverse events following treatment with ipilimumab. We report a 45-year-old male patient with BRAF-mutant metastatic melanoma who discontinued treatment with ipilimumab due to treatment-related grade 3 colitis and was subsequently treated with the anti-programmed cell death 1 protein (PD-1) antibody pembrolizumab. He has been on treatment with pembrolizumab for more than 20 months with no major toxicities and has achieved an objective partial response, which is ongoing.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation.

Aim: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy.

Methods: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk.