FDA Approval Summary: Tremelimumab in Combination with Durvalumab for the Treatment of Patients with Unresectable Hepatocellular Carcinoma.

On October 21, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma. The approval was based on the results from the HIMALAYA study, in which patients with unresectable hepatocellular carcinoma who were naïve to previous systemic treatment were randomly assigned to receive one of three study arms: tremelimumab in combination with durvalumab (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The primary objective of improvement in overall survival (OS) for tremelimumab in combination with durvalumab compared with sorafenib met statistical significance with a stratified HR of 0.78 [95% confidence interval (CI), 0.66-0.92; P = 0.0035]. The median OS was 16.4 months (95% CI, 14.2-19.6) with tremelimumab in combination with durvalumab and 13.8 months (95% CI, 12.3-16.1) with sorafenib. Adverse reactions occurring in ≥20% of patients receiving tremelimumab in combination with durvalumab were rash, fatigue, diarrhea, pruritus, musculoskeletal pain, and abdominal pain. The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg, i.v., as a single dose in combination with durvalumab 1,500 mg at cycle 1/day 1, followed by durvalumab 1,500 mg, i.v., every 4 weeks. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg, i.v., as a single dose in combination with durvalumab 20 mg/kg, i.v., followed by durvalumab 20 mg/kg, i.v., every 4 weeks.

Duodenal Adenocarcinoma in a patient with Lynch Syndrome. A Case Report and Facts Related to Small Intestine Cancer.

Diagnosing small bowel cancer has been challenging due to its unusual presentation and inaccessibility on endoscopy. A 41-year-old male with a history of irritable bowel syndrome underwent esophagogastroduodenoscopy (EGD) for worsening fatigue and lightheadedness despite iron supplements therapy for low hemoglobin. Initial upper endoscopy showed esophagitis and non-bleeding duodenal bulb ulcer with exudate. Endoscopic ultrasound (EUS) with fine-needle aspiration was done due to persistent concern of malignancy and demonstrated moderately differentiated adenocarcinoma in the second portion of the duodenum. Endoscopic ultrasound with fine-needle aspiration may be a superior approach to diagnosing duodenal carcinoma than EGD alone. Small bowel cancer can be a part of the tumor spectrum of Lynch syndrome. Duodenal adenocarcinomas present at a late stage and portend a poor prognosis. We present a case of duodenal adenocarcinoma in an otherwise healthy individual emphasizing the importance of malignancy in the differential and genetic counseling in individuals with the family risk factor.

From Cancer Epidemiology to Policy and Practice: the Role of a Comprehensive Cancer Center.

Purpose of Review: Cancer incidence and mortality are decreasing, but inequities in outcomes persist. This paper describes the San Francisco Cancer Initiative (SF CAN) as a model for the systematic application of epidemiological evidence to reduce the cancer burden and associated inequities. Recent Findings: SF CAN is a multi-institutional implementation of existing evidence on the prevention and early detection of five common cancers (i.e., breast, prostate, colorectal, liver, and lung/tobacco-related cancers) accounting for 50% of cancer deaths in San Francisco. Five Task Forces follow individual logic models designating inputs, outputs, and outcomes. We describe the progress made and the challenges faced by each Task Force after 5 years of activity. Summary: SF CAN is a model for how the nation's Comprehensive Cancer Centers are ideally positioned to leverage cancer epidemiology for evidence-based initiatives that, along with genuine community engagement and multiple stakeholders, can reduce the population burden of cancer.

FDA Approval Summary: Lurbinectedin for the Treatment of Metastatic Small Cell Lung Cancer.

On June 15, 2020, the FDA granted accelerated approval to lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Approval was granted on the basis of the clinically meaningful effects on overall response rate (ORR) and duration of response (DOR), and the safety profile observed in a multicenter, open-label, multicohort clinical trial (PM1183-B-005-14, NCT02454972), referred to as Study B-005, in patients with advanced solid tumors. The trial included a cohort of 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. The confirmed ORR determined by investigator assessment using RECIST 1.1 in the approved SCLC patient population was 35% [95% confidence interval (CI): 26-45], with a median DOR of 5.3 (95% CI: 4.1-6.4) months. The drug label includes warnings and precautions for myelosuppression, hepatotoxicity, and embryo-fetal toxicity. This is the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC. Importantly, this approval includes an indication for patients who have platinum-resistant disease, representing an area of particular unmet need.

A Public Health Perspective on Screening for Psychosis Within General Practice Clinics.

Screening for major mental illness in adolescents and young adults has lagged behind screening for physical illness for a myriad of reasons. Existing pediatric behavioral health screening tools screen primarily for disorders of attention, disruptive behaviors, depression, and anxiety. A few also screen for substance use and suicide risk. Although it is now possible to reliably identify young people at imminent risk for a psychotic disorder, arguably the most severe of mental illnesses, general practitioners (GP) rarely screen for psychotic symptoms or recognize when to refer patients for a specialized risk assessment. Research suggests that barriers such as inadequate knowledge or insufficient access to mental health resources can be overcome with intensive GP education and the integration of physical and mental health services. Under the lens of two public health models outlining the conditions under which disease screening is warranted, we examine additional evidence for and against population-based screening for psychosis in adolescents and young adults. We argue that systematic screening within general health settings awaits a developmentally well-normed screening tool that includes probes for psychosis, is written at a sufficiently low reading level, and has acceptable sensitivity and, in particular, specificity for detecting psychosis and psychosis risk in both adolescents and young adults. As integrated healthcare models expand around the globe and psychosis-risk assessments and treatments improve, a stratified screening and careful risk management protocol for GP settings could facilitate timely early intervention that effectively balances the benefit/risk ratio of employing such a screening tool at the population level.

FDA Approval: Uridine Triacetate for the Treatment of Patients Following Fluorouracil or Capecitabine Overdose or Exhibiting Early-Onset Severe Toxicities Following Administration of These Drugs.

On December 11, 2015, the FDA approved uridine triacetate (VISTOGARD; Wellstat Therapeutics Corporation) for the emergency treatment of adult and pediatric patients following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, and of those who exhibit early-onset, severe, or life-threatening toxicity affecting the cardiac or central nervous system, and/or early onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration. Uridine triacetate is not recommended for the nonemergent treatment of adverse reactions associated with fluorouracil or capecitabine because it may diminish the efficacy of these drugs, and the safety and efficacy of uridine triacetate initiated more than 96 hours following the end of administration of these drugs has not been established. The approval is based on data from two single-arm, open-label, expanded-access trials in 135 patients receiving uridine triacetate (10 g or 6.2 g/m(2) orally every 6 hours for 20 doses) for fluorouracil or capecitabine overdose, or who exhibited severe or life-threatening toxicities within 96 hours following the end of fluorouracil or capecitabine administration. Ninety-six percent of patients met the major efficacy outcome measure, which was survival at 30 days or survival until the resumption of chemotherapy, if prior to 30 days. The most common adverse reactions were vomiting, nausea, and diarrhea. This article summarizes the FDA review of this New Drug Application, the data supporting approval of uridine triacetate, and the unique regulatory situations encountered by this approval. Clin Cancer Res; 22(18); 4545-49. ©2016 AACR.

Understanding and use of nicotine replacement therapy and nonpharmacologic smoking cessation strategies among Chinese and Vietnamese smokers and their families.

INTRODUCTION: Population-based studies have reported high rates of smoking prevalence among Chinese and Vietnamese American men. Although nicotine replacement therapy (NRT) is effective, recommended, and accessible without prescription, these populations underuse NRT for smoking cessation. The aim of this study was to assess understanding and use of NRT and nonpharmacologic treatments among Chinese and Vietnamese American male smokers and their families. METHODS: In-depth qualitative interviews were conducted with 13 smoker-family pairs, followed by individual interviews with each participant. A total of 39 interviews were conducted in Vietnamese or Chinese, recorded, translated, and transcribed into English for analysis. RESULTS: Four themes were identified: use and understanding of NRT, nonpharmacologic strategies, familial and religious approaches, and willpower. Both smokers and their family members believed strongly in willpower and a sense of personal responsibility as the primary drivers for stopping smoking. Lack of these 2 qualities keeps many Chinese and Vietnamese men from using NRT to quit smoking. Those who do use NRT often use it incorrectly, following their own preferences rather than product instructions. CONCLUSION: Our findings indicate the importance of culturally appropriate patient education about NRT. It may be necessary to teach smokers and their families at an individual level about NRT as a complementary approach that can strengthen their resolve to quit smoking. At a community level, public health education on the indication and appropriate use of evidence-based smoking cessation resources, such as NRT, would be an important component of effective tobacco control.

The efficacy of auriculotherapy for smoking cessation: a randomized, placebo-controlled trial.

BACKGROUND: Quitting smoking remains a challenge for almost one-third of the military veteran population. Alternatives to pharmacological therapies such as acupuncture, acupressure, and electrical stimulation have received minimal attention in research but have been widely reported to be popular and safe interventions for smoking cessation. METHODS: This randomized, double-blind, placebo-controlled clinical trial of 125 veterans was conducted to determine whether aural electrical stimulation (auriculotherapy) once a week for 5 consecutive weeks is associated with a higher rate of smoking abstinence are than observed with sham stimulation. RESULTS: Auriculotherapy was found to be safe and largely free from significant side effects. However, there was no difference in the rate of smoking cessation between those participants who received true auriculotherapy and those who received sham auriculotherapy. The auriculotherapy group achieved a rate of 20.9% abstinence versus 17.9% for the placebo arm after 6 weeks. CONCLUSION: The results of this randomized, controlled clinical trial do not support the use of auriculotherapy to assist with smoking cessation. It is possible that a longer treatment duration, more frequent sessions, or other modifications of the intervention protocol used in this study may result in a different outcome. However, based on the results of this study, there is no evidence that auriculotherapy is superior to placebo when offered once a week for 5 weeks, as described in previous uncontrolled studies.