Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival.

The immune checkpoint inhibitor ipilimumab provides long term survival in some metastatic melanoma patients, but the majority has no benefit, and may experience serious side effects. Here, we investigated the dynamics of plasma cytokine concentrations and their potential utility for predicting treatment response, adverse events and overall survival (OS) in patients with metastatic melanoma undergoing ipilimumab monotherapy. A cohort of 148 patients was examined, with plasma samples collected prior to treatment initiation and at the end of the first and second treatment cycles.

Health-Related Quality of Life in Colorectal Cancer Patients Treated With Liver Transplantation Compared to Chemotherapy.

Liver transplantation (LT) for patients with non-resectable colorectal liver metastases (CRLM) offers improved survival and has gained increased interest internationally the last years. The aim of this study was to describe the health-related quality of life (HRQoL) in patients with non-resectable CRLM receiving LT and how baseline HRQoL factors affect overall survival (OS). HRQoL data in the SECA (SEcondary CAncer) LT cohort was compared to data obtained from colorectal cancer patients starting first-line chemotherapy for metastatic disease in a clinical trial and data from a Norwegian normal population.

Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study.

Background: Outcomes in advanced anal squamous cell carcinoma are poor, with few treatment options and controlled clinical trials. We evaluated the efficacy and safety of pembrolizumab in patients with advanced anal squamous cell carcinoma (cohort A) from the phase 2 KEYNOTE-158 study.

Methods: Eligible patients enrolled in the ongoing non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study, which was done across 38 centres worldwide, were aged 18 years or older; had histologically or cytologically confirmed advanced or metastatic anal squamous cell carcinoma; had previous failure of or intolerance to standard therapy or no standard therapy options; and had a PD-L1-evaluable tissue sample.

First-in-human phase 1 dose-escalation study of CAN04, a first-in-class interleukin-1 receptor accessory protein (IL1RAP) antibody in patients with solid tumours.

Background: Interleukin-1 (IL-1) signalling is involved in various protumoural processes including proliferation, immune evasion, metastasis and chemoresistance. CAN04 is a first-in-class monoclonal antibody that binds IL-1 receptor accessory protein (IL1RAP), required for IL-1 signalling. In this first-in-human phase 1 study, we assessed safety, recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of CAN04 monotherapy.

Combining a Universal Telomerase Based Cancer Vaccine With Ipilimumab in Patients With Metastatic Melanoma - Five-Year Follow Up of a Phase I/IIa Trial.

Background: Ipilimumab improves survival for patients with metastatic malignant melanoma. Combining a therapeutic cancer vaccine with ipilimumab may increase efficacy by providing enhanced anti-tumor immune responses. UV1 consists of three synthetic long peptides from human telomerase reverse transcriptase (hTERT).

Clinicopathological factors associated with tumour-specific mutation detection in plasma of patients with RAS-mutated or BRAF-mutated metastatic colorectal cancer.

Detection of tumour-specific circulating cell-free DNA in plasma (ctDNA) fails in a significant number of cases depending on the clinical context. The primary aim was to investigate clinicopathological factors associated with detection of ctDNA in patients with RAS-/BRAF-mutated metastatic colorectal cancer (mCRC) prior to first-line therapy. A secondary aim was to evaluate the prognostic impact of ctDNA compared to other biomarkers.

Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study.

Background: Malignant pleural mesothelioma (MPM) has few treatment options. Pembrolizumab showed preliminary clinical benefit in programmed death ligand 1 (PD-L1)-positive MPM. We evaluated the efficacy and safety of pembrolizumab monotherapy in patients with previously treated MPM irrespective of PD-L1 status in the KEYNOTE-158 study.

Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study.

Purpose: BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with V600E-mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, binimetinib plus cetuximab (ENCO/BINI/CETUX; triplet) and encorafenib plus cetuximab (ENCO/CETUX; doublet) regimens improved overall survival (OS) and objective response rate (ORR; by blinded central review) versus standard of care. The purpose of this analysis was to report updated efficacy and safety data.

Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer.

Unlabelled: Human telomerase reverse transcriptase (hTERT) is a target antigen for cancer immunotherapy in patients with non-small cell lung cancer (NSCLC). We have tested a novel hTERT vaccine, UV1, designed to give high population coverage. UV1 is composed of three synthetic long peptides containing multiple epitopes identified by epitope spreading data from long-term survivors from previous hTERT vaccination trials.

Transplant oncology: assessment of response and tolerance to systemic chemotherapy for metastatic colorectal cancer after liver transplantation - a retrospective study.

Solid organ recipients have a 2-5 fold increased risk of malignancy compared to the general population. Because of the broader indications for transplantation, it is anticipated that an increasing number of organ graft recipients will present with malignancy. There are limited data about responses and tolerance to chemotherapy in solid organ transplanted patients.

Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome.

Background: Mutation status of RAS and BRAF, as well as serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), are biomarkers used in clinical management of patients with gastrointestinal cancers. This study aimed to examine the prognostic role of these biomarkers in a patient population that started first-line chemotherapy for unresectable metastatic colorectal cancer (mCRC) in the NORDIC-VII study.

Methods: CEA and CA 19-9 were measured in serum samples from 545 patients obtained before the start of chemotherapy.

Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer.

Claudin-2 is a trans-membrane protein-component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome.

Health-related quality of life in patients with metastatic colorectal cancer, association with systemic inflammatory response and RAS and BRAF mutation status.

Background: The aim of this study was to evaluate the effect of cetuximab on health-related quality of life (HRQoL) in the NORDIC-VII trial on metastatic colorectal cancer (mCRC), and to assess HRQoL in relation to RAS and BRAF mutation status and inflammatory biomarkers.

Patient And Methods: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, after every fourth cycle of chemotherapy, and at the end of treatment. HRQoL during 12 cycles of chemotherapy was evaluated over time, compared between treatment arms, and assessed for association with tumour mutation status and inflammatory markers.

Cetuximab in treatment of metastatic colorectal cancer: final survival analyses and extended RAS data from the NORDIC-VII study.

Background: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis.

Methods: A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study.

Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer.

Objectives: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status.

Results: High levels of pretreatment serum IL-6 or CRP were associated with impaired outcome, in terms of reduced PFS and OS. Patients with low versus high serum IL-6 levels had median OS of 26.

Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer.

Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown.Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC).

Is Liver Transplantation an Option in Colorectal Cancer Patients with Nonresectable Liver Metastases and Progression on All Lines of Standard Chemotherapy?

Background: About 50 % of patients with metastatic colorectal cancer (CRC) will develop metastatic disease with liver as primary metastatic site. The majority of CRC patients has nonresectable disease and receives palliative chemotherapy. Overall survival (OS) from time of progression on last line of chemotherapy in metastatic CRC is about 5 months.