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.

Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial.

KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS-MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC.

Transcriptomic subtyping of malignant peripheral nerve sheath tumours highlights immune signatures, genomic profiles, patient survival and therapeutic targets.

Background: Malignant peripheral nerve sheath tumour (MPNST) is an aggressive orphan disease commonly affecting adolescents or young adults. Current knowledge of molecular tumour biology has been insufficient for development of rational treatment strategies. We aimed to discover molecular subtypes of potential clinical relevance.

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study.

Background: The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers.

Methods: Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Characterization of the T cell receptor repertoire and melanoma tumor microenvironment upon combined treatment with ipilimumab and hTERT vaccination.

Background: This clinical trial evaluated a novel telomerase-targeting therapeutic cancer vaccine, UV1, in combination with ipilimumab, in patients with metastatic melanoma. Translational research was conducted on patient-derived blood and tissue samples with the goal of elucidating the effects of treatment on the T cell receptor repertoire and tumor microenvironment.

Methods: The trial was an open-label, single-center phase I/IIa study.

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.

Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials.

Background: Therapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple indications. Although telomerase is a near-universal tumor target, different treatment combinations applied across indications may affect the induced immune response.

Improving public cancer care by implementing precision medicine in Norway: IMPRESS-Norway.

Background: Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tissue. Targeted therapies interfering with cancer specific pathways have been developed and approved for subgroups of patients.

Circulating tumour DNA and its clinical utility in predicting treatment response or survival in patients with metastatic colorectal cancer: a systematic review and meta-analysis.

Background: We investigate the current knowledge on circulating tumour DNA (ctDNA) and its clinical utility in predicting outcomes in patients with metastatic colorectal cancer (mCRC).

Methods: PubMed, Embase, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials were searched. Last search 16/12/2020.

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.

Survival Trends of Right- and Left-Sided Colon Cancer across Four Decades: A Norwegian Population-Based Study.

Background: Patients with right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ clinically and molecularly. The main objective was to investigate stage-stratified survival and recurrence of RCC and LCC across four 10-year periods.

Methods: Patients diagnosed from 1977 to 2016 with colon adenocarcinoma were included from the Cancer Registry of Norway.

Ipilimumab in a real-world population: A prospective Phase IV trial with long-term follow-up.

Ipilimumab was the first treatment that improved survival in advanced melanoma. Efficacy and toxicity in a real-world setting may differ from clinical trials, due to more liberal eligibility criteria and less intensive monitoring. Moreover, high costs and lack of biomarkers have raised cost-benefit concerns about ipilimumab in national healthcare systems and limited its use.

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.

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial.

Aim: To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma.

Material And Methods: The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.

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.

Patient-Derived Organoids from Multiple Colorectal Cancer Liver Metastases Reveal Moderate Intra-patient Pharmacotranscriptomic Heterogeneity.

Purpose: Molecular tumor heterogeneity may have important implications for the efficacy of targeted therapies in metastatic cancers. Inter-metastatic heterogeneity of sensitivity to anticancer agents has not been well explored in colorectal cancer.

Experimental Design: We established a platform for pharmacogenomic profiling of patient-derived organoids (PDO) from resected colorectal cancer liver metastases.