Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.

Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti­programmed cell death 1 (anti­PD-1)­based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ­positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.

Women in oncology pharmacy leadership: A white paper.

Gender disparity exists in leadership roles within healthcare. While the majority of the healthcare workforce is comprised of women, significantly fewer women occupy leadership positions, particularly at executive and board levels. As the field of oncology pharmacy continues to rapidly expand and evolve, an assessment of the current state of women in oncology pharmacy leadership roles is vital to the growth and development of the profession. In the fall of 2017, the Hematology/Oncology Pharmacy Association (HOPA) hosted a summit to explore leadership issues facing women in oncology pharmacy which have the potential to affect our membership and our profession. This meeting included invited participants from across the fields of oncology and pharmacy and was part of HOPA's strategic leadership initiative developed through the work of the HOPA Leadership Development Committee in 2016. This promotes a primary goal of HOPA, which is to support oncology pharmacists as they assume leadership roles within their practices and within healthcare to assure oncology pharmacy is integrated into cancer care. The purpose of this white paper is to (1) summarize key issues that were identified through a membership survey; (2) review ongoing efforts to address the needs of female oncology pharmacists in leadership development; (3) serve as a call to action for individuals and professional organizations to assist with and disseminate these efforts and highlight available resources, and (4) to provide practical steps to meet the needs of individuals, training programs, and institutions/employers.

Elucidating somatization in a dimensional model of psychopathology across medical settings.

Research using a categorical-polythetic classification system for mental illness has raised concern regarding the validity of categorical classification systems. Recent efforts suggest psychopathology is better understood from a dimensional framework, though there has been varying evidence of a somatization factor. The current investigation seeks to produce and validate a dimensional model of psychopathology, with a particular emphasis on the placement of somatization, across three nonoverlapping medical samples. Using a bariatric surgery seeking sample (n = 1,268), a spine surgery/spinal cord stimulator seeking sample (n = 1,711), and a chronic pain treatment seeking sample (n = 1,388), a dimensional model of psychopathology was replicated across all three samples using a dimensional measure of psychopathology (the Minnesota Multiphasic Personality Inventory-2-Restructured Form [MMPI-2-RF]). Clear evidence of a separate somatization factor was found in addition to broad internalizing, externalizing, and social detachment factors. Constructs assessable with the model yielded good convergent and discriminant validity coefficients with external criteria, and further supported the presence of a higher-order somatization construct. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Correction to: Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis.

Following publication of the original article [1], the authors reported an error in their listed affiliations.

Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis.

BACKGROUND: Immune-related enterocolitis (irEC) is the most common serious complication from checkpoint inhibitors (CPIs). The current front-line treatment for irEC, high-dose corticosteroids (CS), have significant side effects and prolonged therapy may reduce CPI-anti-tumor activity. Early addition of TNF-α inhibitors such as infliximab (IFX) may expedite symptom resolution and shorten CS duration. Thus, we conducted the first retrospective study, to our knowledge, evaluating symptom resolution in patients with irEC treated with and without IFX. METHODS: Data were collected from the medical records of patients diagnosed with irEC. The primary endpoint was time to symptom resolution for irEC for cases managed with IFX plus CS (IFX group) versus CS alone (CS group). Duration of CS, overall survival (OS), and time to treatment failure (TTF) were secondary endpoints. RESULTS: Among 75 patients with irEC, 52% received CS alone, and 48% received IFX. Despite higher grade colitis in the IFX group (grade 3/4: 86% vs. 34%; p < 0.001), median times to diarrhea resolution (3 vs. 9 days; p < 0.001) and to steroid titration (4 vs. 13 days; p < 0.001) were shorter in the IFX group than in the CS group without a negative impact on TTF or OS. Total steroid duration (median 35 vs. 51 days; p = 0.150) was numerically lower in the IFX group. CONCLUSIONS: Despite higher incidence of grade 3/4 colitis, IFX added to CS for the treatment of patients with irEC was associated with a significantly shorter time to symptom resolution. The data suggest that early introduction of IFX should be considered for patients with irEC until definitive prospective clinical trials are conducted.

A practical guide for the safe implementation of early phase drug development and immunotherapy program in gynecologic oncology practice.

The success of targeted and immune therapies in other malignancies has led to an exponential increase in the number of active and pending clinical trials using these therapeutic approaches in patients with gynecologic cancers. These novel investigational agents are associated with unique and potentially life-threatening toxicities and many require special multidisciplinary logistical considerations. The objective of this review is to describe a practical approach for the safe implementation of targeted and immune therapies in academic gynecologic oncology practices based on our experience at M.D. Anderson Cancer Center.

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma.

OBJECTIVE: To summarize the clinical development of avelumab and its clinical relevance in metastatic Merkel cell carcinoma (MCC). DATA SOURCES: An English-language literature search using PubMed was performed using the terms avelumab, anti-PD-1, anti-PD-L1, and MCC from January of 1950 to March 2018. Data were also obtained from package inserts, meeting abstracts, and clinical registries. STUDY SELECTION/DATA EXTRACTION: All relevant published articles of avelumab were reviewed. Clinical trial registries and meeting abstracts were used for information about ongoing trials. DATA SYNTHESIS: Avelumab is a fully human monoclonal antibody that inhibits programmed death ligand-1, which reverses T-cell exhaustion and induces antitumor responses. Avelumab is safe and effective in previously treated metastatic MCC based on a phase II trial of previously treated patients with objective response rates in 28 of 88 patients, including 10 complete responses and 19 partial responses. Median overall survival (OS) was 12.9 months, and 1-year progression-free survival and OS were 30% and 52%, respectively. Grade 3 treatment-related side effects included lymphopenia (2 patients), serum creatine phosphokinase increase (1 patient), aminotransferase elevation (1 patient), and serum cholesterol increase (1 patient). Relevance to Patient Care and Clinical Practice: This review outlines the pharmacology and clinical trial data for avelumab in metastatic MCC and guides clinicians on avelumab's place in therapy. CONCLUSIONS: Avelumab is the first Food and Drug Administration-approved medication for metastatic MCC and provides an advantage of durable responses and possibly improved tolerability compared with traditional platinum-based chemotherapy. Clinical trials are under way to expand its utility into the adjuvant and frontline settings.

Immunotherapy for uveal melanoma.

Uveal melanoma (UM) is a rare cancer with a high mortality rate. In comparison to cutaneous melanoma, UM has unique immunological features. Arising in the immune suppressive environment of the eye, it maintains immune resistance once metastatic. This is considered a major obstacle for successful immunotherapy in UM. However, a growing body of evidence suggests strategies that may abrogate resistance and enhance antitumor immunity in UM. Recently, three new immune agents have been approved for melanoma. While these drugs demonstrate durable clinical responses with long-term remissions in metastatic cutaneous melanoma, only limited data exist in metastatic UM. In this review, immunological aspects of UM and data from clinical studies of immunotherapeutic agents and regimens for UM will be discussed.

Anti-programmed cell death-1 (PD-1) monoclonal antibodies in treating advanced melanoma.

The anti-programmed cell death-1 (PD-1) monoclonal antibodies pembrolizumab and nivolumab have been contingently approved for the treatment of patients with advanced melanoma based on their durable response, high response rate, and favorable safety profile. Mature survival data from randomized phase III trials are eagerly awaited to confirm their position as the standard-of-care frontline or second-line therapy in advanced melanoma management algorithm. The immune-related adverse events associated with these novel agents are somewhat different than those of ipilimumab, considering the manifestation of pneumonitis and acute renal failure. Active research is ongoing to identify biomarkers predictive of clinical benefit to the anti-PD1 monoclonal antibodies, to expand their utility in other disease settings, and to explore their safety and efficacy in combination with other therapeutic agents. Unanswered questions concerning optimal dosing schedule, treatment duration, and therapy sequencing will also need to be addressed in future investigations.

Tools to expedite the development of treatment plans.

Quality improvement strategies can be used to modify existing health care processes to reduce patient wait times. We undertook a quality improvement project to reduce the time between new patients' initial visits and the finalization of their treatment plans. Initiation of treatment of new patients at the MD Anderson Sarcoma Medical Oncology Clinic can take up to 2 weeks from their initial consultation. Treatment delays result in increased costs and anxiety for the patient, adversely affecting the quality of care provided. We performed detailed process mapping and a cause-and-effect analysis to identify and prioritize opportunities for improvement. Process improvements addressed 2 key causes of delay to develop a finalized treatment plan: (1) insufficient data for decision making at the time of new patient visit and (2) delays in obtaining diagnostic imaging. After implementing our process improvements, the median time to develop a treatment plan decreased by 89% from 70.5 to 7.6 hours. Our process changes involved minimal additional work and had the secondary outcome of resulting in time savings for the clinic team.

New and emerging therapies for advanced or metastatic soft tissue sarcoma.

Soft tissue sarcomas include a rare variety of tumors, which require a multidisciplinary approach to treatment. Patients with advanced or metastatic disease are typically treated with anthracycline-based therapy, but these chemotherapy regimens are associated with poor response rates and average survival duration of one year. Much attention has been turned toward overexpressed gene pathways, and utilizing targeted therapies to inhibit tumor growth. Many new and approved targeted therapies and chemotherapy agents are currently in clinical and preclinical studies for soft tissue sarcoma. As the results of these studies are reported, we hope to see improved response rates and less toxicity, both in the frontline setting and for patients with advanced disease. This article will review the available data for some of the more promising therapies for advanced or metastatic soft tissue sarcomas.

Dabrafenib therapy for advanced melanoma.

OBJECTIVE: To summarize the clinical development of dabrafenib and to highlight the clinically relevant distinct characteristics of dabrafenib in contrast to vemurafenib. DATA SOURCE: An English-language literature search of MEDLINE/PubMed (1966-June 2013), using the keywords GSK2118436, dabrafenib, vemurafenib, selective BRAF inhibitor, and advanced melanoma, was conducted. Data were also obtained from package inserts, meeting abstracts, and clinical registries. STUDY SELECTION AND DATA EXTRACTION: All relevant published articles on dabrafenib and vemurafenib were reviewed. Clinical trial registries and meeting abstracts were used for information about ongoing studies. DATA SYNTHESIS: BRAF(V600E) mutation confers constitutive BRAK kinase activation in melanoma cells, promoting tumor growth. This discovery led to the development of BRAF kinase inhibitors like vemurafenib and dabrafenib. Dabrafenib has been approved to treat patients with BRAF(V600E)-positive unresectable or metastatic melanoma based on its clinical benefit demonstrated in a randomized phase III study. It has also been shown to be safe and effective in patients with BRAF mutant advanced melanoma involving the brain. Dabrafenib is well tolerated, with the most common adverse effects being hyperkeratosis, headache, pyrexia, and arthralgia. Currently, there is no evidence to suggest that one BRAF inhibitor is superior to the other. With similar efficacy, therapy selection will likely be influenced by differential tolerability and cost. CONCLUSIONS: Dabrafenib joins vemurafenib to confirm the superior clinical outcome of the BRAF inhibitors when compared with dacarbazine in patients with BRAF(V600E)-positive advanced melanoma. Active research is ongoing to expand its utility into the adjuvant setting and to circumvent rapid emergence of drug resistance.

Labile iron in parenteral iron formulations: a quantitative and comparative study.

BACKGROUND: Evidence of iron-mediated oxidative stress, neutrophil dysfunction and enhanced bacterial growth after intravenous (IV) iron administration has been ascribed to a labile or bioactive iron fraction present in all IV iron agents. METHODS: To quantify and compare the size of the labile fraction in several classes of IV iron agents, we examined iron donation to transferrin (Tf) in vitro. We added dilutions of ferric gluconate, iron sucrose and each of two iron dextran preparations to serum in vitro, passed the resulting samples through alumina columns to remove iron agent and free organic iron, and measured Tf-bound iron in the resulting eluates. Comparing results to serum samples without added iron, we calculated delta Tf-bound iron for each agent at each concentration. Finally, we compared delta Tf-bound iron to the concentration of added agent and calculated the percent iron donation to Tf. RESULTS: We found that Tf-bound iron increased with added iron concentration for each agent: delta Tf-bound iron was directly related to the concentration and type of iron agent (P<0.001). Mean percent iron donation to Tf ranged from 2.5 to 5.8% with the following progression: iron dextran-Dexferrum