Safety and tolerability of mirvetuximab soravtansine monotherapy for folate receptor alpha-expressing recurrent ovarian cancer: An integrated safety summary.

Objective: Mirvetuximab soravtansine-gynx (MIRV) is a novel antibody-drug conjugate targeting folate receptor alpha (FRα), which is overexpressed in epithelial ovarian cancer (EOC), with limited expression on normal tissues. This integrated safety summary sought to characterize the safety profile of MIRV monotherapy in participants with FRα-expressing recurrent EOC.

Methods: Safety data were retrospectively analyzed from 4 clinical studies (phase 1 trial [NCT01609556], phase 3 FORWARD I [NCT02631876], phase 2 SORAYA [NCT04296890], phase 3 MIRASOL [NCT04209855]) that evaluated participants with FRα-expressing recurrent EOC who received ≥1 dose of MIRV 6 mg/kg adjusted ideal body weight every 3 weeks.

Breast cancer outcomes in a private hospital appear better than national outcomes in a country with a mixed public/private healthcare model.

Background: Ireland has a mixed model of healthcare delivery with a public healthcare system funded by general taxation and a large private healthcare insurance system, covering 43% of the population in 2012 and 2016. We set out to examine disparities in outcomes among patients with breast cancer treated in a private hospital compared to national outcomes over a comparable period.

Methods: Medical records of patients diagnosed with early (Stage 1-3 as per AJCC version 5) breast cancer between 2010 and 2015 at Bon Secours Hospital, Cork, Ireland were reviewed.

Cancer-related fatigue and self-care agency: A multicentre survey of patients receiving chemotherapy.

Aims And Objectives: To measure cancer-related fatigue (CRF), self-care agency (SCA) and fatigue self-care strategies, and to explore the relationship between CRF and SCA.

Background: Cancer-related fatigue has been consistently rated as the most elusive, common and severe of symptoms that patients with cancer undergoing chemotherapy experience. Despite its frequency and severity, CRF is poorly managed.

The Role of CDK4/6 Inhibitors in Breast Cancer.

Oral inhibitors of CDK4/6 have been shown to increase response rates and prolong disease control when combined with endocrine therapy in hormone-responsive (HR+) HER2-negative advanced breast cancer. Palbociclib, ribociclib and abemaciclib are all approved in combination with non-steroidal aromatase inhibitors in first-line therapy for post-menopausal women, with a 40-45% improvement in progression-free survival seen with the addition of any of these CDK4/6 inhibitors. Additional approved indications, including first- and second-line combination therapy for pre-menopausal women, combination with fulvestrant and use as monotherapy, vary with each agent and are reviewed fully in the subsequent texts.

Patients with colorectal lung oligometastases (L-OMD) treated by dose adapted SABR at diagnosis of oligometastatic disease have better outcomes than patients previously treated for their metastatic disease.

Aim: To evaluate the clinical outcomes of patients with OMD from a CRC primary, who underwent SABR either as first treatment at diagnosis of metachronous oligometastatic disease to lung or at progression in lung after prior treatments for metastatic disease.

Methods: This is a retrospective review of 60 patients with 85 lung oligometastases treated by SABR at two institutions, between May 2009 and September 2014. Local control (LC), overall survival (OS), progression - free survival (PFS), and toxicity were evaluated.

PARP Inhibitors in Clinical Use Induce Genomic Instability in Normal Human Cells.

Poly(ADP-ribose) polymerases (PARPs) are the first proteins involved in cellular DNA repair pathways to be targeted by specific inhibitors for clinical benefit. Tumors harboring genetic defects in homologous recombination (HR), a DNA double-strand break (DSB) repair pathway, are hypersensitive to PARP inhibitors (PARPi). Early phase clinical trials with PARPi have been promising in patients with advanced BRCA1 or BRCA2-associated breast, ovary and prostate cancer and have led to limited approval for treatment of BRCA-deficient ovary cancer.

Endocrine resistance in hormone-responsive breast cancer: mechanisms and therapeutic strategies.

The majority of breast cancers may be considered hormone responsive due to expression of hormone receptors (HR+). Although endocrine therapy is always considered for advanced HR+ breast cancer, the emergence of resistance is inevitable over time and is present from the start in a proportion of patients. In this review, we explore the mechanisms underlying de novo and acquired resistance to endocrine therapy.

CDK4/6 inhibitors in breast cancer.

Deregulation of the cyclin-dependent kinase (CDK) 4/6-retinoblastoma (RB) axis can occur through a number of mechanisms and contributes towards the unrestrained growth witnessed in a variety of cancers including breast cancers. Recent years have seen the development of selective CDK4/6 inhibitors, which have delivered promising preclinical and clinical results in breast cancer and other tumours. A number of trials assessing antitumour efficacy in various disease settings and combinations are ongoing.

Prognostic significance of prospectively detected bone marrow micrometastases in esophagogastric cancer: 10-year follow-up confirms prognostic significance.

We have previously reported that most patients with esophagogastric cancer (EGC) undergoing potentially curative resections have bone marrow micrometastases (BMM). We present 10-year outcome data of patients with EGC whose rib marrow was examined for micrometastases and correlate the findings with treatment and conventional pathologic tumor staging. A total of 88 patients with localized esophagogastric tumors had radical en-bloc esophagectomy, with 47 patients receiving neoadjuvant (5-fluorouracil/cisplatin based) chemoradiotherapy (CRT) and the remainder being treated with surgery alone.

The Role of CDK4/6 Inhibition in Breast Cancer.

Imbalance of the cyclin D and cyclin-dependent kinase (CDK) pathway in cancer cells may result in diversion away from a pathway to senescence and toward a more proliferative phenotype. Cancer cells may increase cyclin D-dependent activity through a variety of mechanisms. Therapeutic inhibition of CDKs in tumors to negate their evasion of growth suppressors has been identified as a key anticancer strategy.

Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study.

Background: Breast cancer brain metastases (BCBM) are challenging complications that respond poorly to systemic therapy. The role of the blood-tumor barrier in limiting BCBM drug delivery and efficacy has been debated. Herein, we determined tissue and serum levels of capecitabine, its prodrug metabolites, and lapatinib in women with BCBM resected via medically indicated craniotomy.

Recent advances in novel targeted therapies for HER2-positive breast cancer.

The monoclonal antibody trastuzumab has improved the outcomes of patients with breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2). However, despite this advancement, many tumors develop resistance and novel approaches are needed. Recently, a greater understanding of cellular biology has translated into the development of novel anti-HER2 agents with varying mechanisms of action.

Limited overall survival in patients with brain metastases from triple negative breast cancer.

Patients with breast cancer, which lacks ER, PR, and HER2; "triple negative" (TNBC), are at increased risk of brain metastases (BMs). However, the impact of modern therapy on the risk of BMs and outcomes remains largely unknown. In this retrospective, single-institution study we assessed the incidence of BMs, the therapeutic options, and overall survival, in a recent cohort of patients with TNBC.

HER2-positive breast cancer: beyond trastuzumab.

The outlook for patients with HER2-positive breast cancer was revolutionized by the development of trastuzumab (Herceptin), a humanized murine monoclonal antibody. Use of this agent led to improved overall survival when it was added to chemotherapy for the treatment of metastatic breast cancer. Improved understanding of mechanisms of resistance to trastuzumab has facilitated the development of novel agents for HER2-positive breast cancer, and also resulted in superior outcomes when added to chemotherapy in the adjuvant setting.

BRCA gene structure and function in tumor suppression: a repair-centric perspective.

Germline mutations in the BRCA1 and BRCA2 genes are characterized by deficient repair of DNA double-strand breaks by homologous recombination. Defective DNA double-strand break repair has been not only implicated as a key contributor to tumorigenesis in mutation carriers but also represents a potential target for therapy. The transcriptional similarities between BRCA1-deficient tumors and sporadic tumors of the basal-like subtype have led to the investigation of homologous recombination repair-directed therapy in triple-negative tumors, which demonstrates overlap with the basal-like subtype.

HER2 breast cancer therapies: a review.

Amplification of the HER2 gene and/or overexpression of its protein product have been found in up to 25% to 30% of human breast cancers and have been shown to be associated with poorer outcomes compared to 'HER2 normal' breast cancer. Research has focused on developing therapies directed to the HER2 receptor and its pathway. These include the monoclonal antibody trastuzumab, which has improved outcomes when used in patients with both advanced and early breast cancer.

Evolving approaches to metastatic breast cancer previously treated with anthracyclines and taxanes.

Despite major advances in the adjuvant treatment of breast cancer, many women will develop metastatic disease, either de novo or following optimal adjuvant therapy. Further effective therapeutic options are needed for women who progress following anthracycline- and taxane-containing regimens. Capecitabine is approved by the US Food and Drug Administration as monotherapy in this setting.