Therapeutic Advances in Medical Oncology

BACKGROUND AND AIMS: Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen (oxaliplatin plus fluorouracil and leucovorin) is a promising option for large hepatocellular carcinoma (HCC). However, post-HAIC prognosis can vary in different patients due to tumor heterogeneity. Herein, we established two nomogram models to assess the survival prognosis of patients after HAIC combination therapy. METHODS: A total of 1082 HCC patients who underwent initial HAIC were enrolled between February 2014 and December 2021...

BACKGROUND: Advanced triple-negative breast cancer (aTNBC) has a poor prognosis; thus, there is a need to identify novel biomarkers to guide future research and improve clinical outcomes. OBJECTIVES: We tested the prognostic ability of an emerging, complete blood count (CBC)-based inflammatory biomarker, the pan-immune-inflammation value (PIV), in patients with aTNBC treated with first-line, platinum-based chemotherapy. DESIGN: This was a retrospective, monocentric, observational study...

[This retracts the article DOI: 10.1177/1758835920965853.].

Breast cancer (BC) is the most commonly diagnosed cancer worldwide. Advanced BC with brain metastasis (BM) is a major cause of mortality with no specific or effective treatment. Therefore, better knowledge of the cellular and molecular mechanisms underlying breast cancer brain metastasis (BCBM) is crucial for developing novel therapeutic strategies and improving clinical outcomes. In this review, we focused on the latest advances and discuss the contribution of the molecular subtype of BC, the brain microenvironment, exosomes, miRNAs/lncRNAs, and genetic background in BCBM...

BACKGROUND: Epidermal growth factor receptor (EGFR) is a well-known target for cancer treatment. However, the authorized anti-EGFR monoclonal antibodies generally cause several toxic effects, especially severe cutaneous toxicities as well as infusion reactions, and the clinical indications are limited. Here we developed Ametumumab, a fully human recombinant anti-EGFR monoclonal antibody. OBJECTIVES: To assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity of Ametumumab...

BACKGROUND: The current model of clinical drug development in oncology displays major limitations due to a high attrition rate in patient enrollment in early phase trials and a high failure rate of drugs in phase III studies. OBJECTIVE: Integrating transcriptomics for selection of patients has the potential to achieve enhanced speed and efficacy of precision oncology trials for any targeted therapies or immunotherapies. METHODS: Relative gene expression level in the metastasis and normal organ-matched tissues from the WINTHER database was used to estimate in silico the potential clinical benefit of specific treatments in a variety of metastatic solid tumors...

BACKGROUND: To investigate the prognostic role of pretreatment squamous cell carcinoma antigen (SCCA) in early-stage cervical cancer (CC). METHODS: We enrolled 487 cases of pathology-proven early-stage [International Federation of Gynecology and Obstetrics (FIGO) I/II] squamous or adenosquamous CC that were treated from 2012 to 2015. Restricted cubic splines (RCS) with a full Cox regression model were used to evaluate the association between SCCA levels and survival outcomes...

Uterine sarcomas are very infrequent and heterogeneous entities. Due to its rarity, pathological diagnosis, surgical management, and systemic treatment are challenging. Treatment decision process in these tumors should be taken in a multidisciplinary tumor board. Available evidence is low and, in many cases, based on case series or clinical trials in which these tumors have been included with other soft tissue sarcoma. In these guidelines, we have tried to summarize the most relevant evidence in the diagnosis, staging, pathological disparities, surgical management, systemic treatment, and follow-up of uterine sarcomas...

Cervical cancer still represents a major public health problem, being the fourth most common cancer in incidence and mortality in women worldwide. These figures are unacceptable since cervical cancer, an human papillomavirus-related malignancy, is a largely preventable disease by means of well-established screening and vaccination programs. Patients with recurrent, persistent, or metastatic disease unsuitable for curative therapeutic approaches represent a dismal prognosis population. Until recently, these patients were only candidates for cisplatin-based chemotherapy plus bevacizumab...

High microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) phenotype is a distinct molecular signature across gastrointestinal cancers characterized by high tumor mutational burden and high neoantigen load. Tumors harboring dMMR are highly immunogenic and heavily infiltrated by immune cells; consequently, they are uniquely vulnerable to therapeutic strategies enhancing immune antitumor response such as checkpoint inhibitors. The MSI-H/dMMR phenotype arose as a powerful predictor of response to immune checkpoint inhibitors with evidence supporting significantly improved outcomes in the metastatic setting...

The advent of immune checkpoint inhibition has pushed the treatment paradigm for resectable non-small-cell lung cancer (NSCLC) toward neoadjuvant therapy. A growing number of promising trials have examined the utility of neoadjuvant immunotherapy, both alone and in combination with other modalities such as radiation therapy (RT) and chemotherapy. The phase II LCMC3 and NEOSTAR trials demonstrated a role for neoadjuvant immunotherapy in inducing meaningful pathologic responses, and another phase II trial established the feasibility of combining neoadjuvant durvalumab with RT...

Biliary tract cancers (BTCs) are rare and heterogeneous malignant tumours including cholangiocarcinoma and gallbladder cancer. They are very aggressive, often refractory to chemotherapy and associated with an overall poor prognosis. Surgical resection remains the only potentially curative treatment option but less than 35% present with resectable disease. Adjuvant treatments have been widely used but until recently, supportive data were limited to non-randomised, non-controlled retrospective studies. Recent evidence from the BILCAP trial has established adjuvant capecitabine as the standard of care...

BACKGROUND: Orally administrated agents play a key role in the management of prostate cancer, providing a convenient and cost-effective treatment option for patients. However, they are also associated with adherence issues which can compromise therapeutic outcomes. This scoping review identifies and summarizes data on adherence to oral hormonal therapy in advanced prostate cancer and discusses associated factors and strategies for improving adherence. METHODS: PubMed (inception to 27 January 2022) and conference databases (2020-2021) were searched to identify English language reports of real-world and clinical trial data on adherence to oral hormonal therapy in prostate cancer using the key search terms 'prostate cancer' AND 'adherence' AND 'oral therapy' OR respective aliases...

BACKGROUND: Chemotherapy options in patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of standard chemotherapies are limited. OBJECTIVES: We aimed to report the efficacy and safety of the leucovorin and 5-fluorouracil (LV5FU2) and carboplatin combination in this setting. DESIGN: We performed a retrospective study including consecutive patients with advanced PDAC who received LV5FU2-carboplatin between 2009 and 2021 in an expert center...

OBJECTIVES: The study aims to evaluate the efficacy and safety of thoracic radiotherapy in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-treated patients with stage IV non-small-cell lung cancer (NSCLC). METHODS: Patients with non-oligometastatic NSCLC harboring EGFR mutations were recruited. All patients received the first-generation TKI treatment with or without radiotherapy. The irradiated sites included primary and/or metastatic lesions...

Tebentafusp is a first-in-class immunotherapy agent that comprises an engineered T-cell receptor targeting a gp100 epitope presented by human leukocyte antigen-A*02:01 cells, fused to an anti-CD3 single-chain variable fragment. Tebentafusp is both the first bispecific T-cell engager to show efficacy in the treatment of advanced solid cancer and the first anti-cancer treatment to demonstrate an overall survival benefit in patients with uveal melanoma (UM). This review article will focus on the clinical development of tebentafusp, the mechanism of action and resultant evolution of the management of advanced UM...

Many patients with cancer search for and use alternative and complementary treatments, aiming to improve the effectiveness of their anticancer treatment and a reduction in treatment-associated side effects. Short-term fasting (STF) and fasting mimicking diets (FMDs) are among the most commonly used dietary interventions. In recent years, different trials have reported the promising results of dietary interventions in combination with chemotherapy, in terms of slowing down tumor growth and reduction in chemotherapy-related side effects...

BACKGROUND: Treatment of advanced or metastatic esophageal adenocarcinoma (EAC) follows the guidelines for gastroesophageal junction adenocarcinoma (GEJC) and gastric adenocarcinoma (GAC), but patients with EAC are often excluded from clinical studies of GEJC/GAC. OBJECTIVES: Here we describe treatment and survival of patients with advanced EAC, GEJC, and GAC to provide population-based evidence on distinctions and similarities between these populations. DESIGN: Retrospective cohort study of patients with unresectable advanced (cT4b) or metastatic (cM1) EAC, GEJC, or GAC (2015-2020) were selected from the Netherlands Cancer Registry...

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Kirsten rat sarcoma viral oncogene homolog mutations are observed in 25% of lung adenocarcinoma and 40% of these are G12C mutations. Historically, no approved targeted agents were available for patients with any KRAS mutation, and response rates to standard-of-care therapies were suboptimal. Newly developed inhibitors directed toward KRASG12C have been successful in clinical trials with overall response rates ranging between 32% and 46%, and two FDA approvals were granted in May 2021 and December 2022 as second-line or later monotherapies...