US Food and Drug Administration Approval Summary: Eflornithine for High-Risk Neuroblastoma After Prior Multiagent, Multimodality Therapy.

On December 13, 2023, the US Food and Drug Administration (FDA) approved eflornithine (IWILFIN, US WorldMeds) to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. The approval was based on an externally controlled trial (ECT) consisting of a single-arm trial, study 3(b), compared with an external control (EC) derived from a National Cancer Institute/Children's Oncology Group-sponsored clinical trial (Study ANBL0032) and supported by confirmatory evidence. In the protocol-specified primary analysis, the event-free survival hazard ratio (HR) was 0.

FDA Approval Summary: Atezolizumab as Adjuvant Treatment following Surgical Resection and Platinum-Based Chemotherapy for Stage II to IIIA NSCLC.

On October 15, 2021, the FDA approved atezolizumab as adjuvant therapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have programmed cell death ligand 1 (PD-L1) expression on ≥1% of tumor cells (TC), as detected by an FDA-approved test. The approval was based on results from the IMpower010 trial, in which 1,005 patients with NSCLC who had completed tumor resection and cisplatin-based adjuvant chemotherapy were randomly assigned 1:1 to receive atezolizumab for 16 cycles or best supportive care. The primary endpoint of disease-free survival (DFS) as assessed by investigator was tested hierarchically in the following analysis populations: stage II-IIIA NSCLC with PD-L1 expression on ≥1% of TCs (PD-L1 ≥ 1% TC); all randomly assigned patients with stage II-IIIA NSCLC; and the intent-to-treat population comprising all randomly assigned patients.

A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores.

Purpose: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk.

Methods: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included.

Subgroup Analyses in Oncology Trials: Regulatory Considerations and Case Examples.

Subgroup analyses are assessments of treatment effects based on certain patient characteristics out of the total study population and are important for interpretation of pivotal oncology trials. However, appropriate use of subgroup analyses results for regulatory decision-making and product labeling is challenging. Typically, drugs approved by the FDA are indicated for use in the total patient population studied; however, there are examples of restriction to a subgroup of patients despite positive study results in the entire study population and also extension of an indication to the entire study population despite positive results appearing primarily in one or more subgroups.

Adaptive group-sequential design with population enrichment in phase 3 randomized controlled trials with two binary co-primary endpoints.

The use of co-primary endpoints in drug development allows investigators to capture an experimental intervention's multidimensional effect more comprehensively than a single primary endpoint. We propose the theoretical basis and development of an adaptive population enrichment design with co-primary endpoints, provide stage-wise boundary values for futility and efficacy, and discuss power under different efficacy configurations, subgroup prevalence, and analysis times using a pre-specified decision criterion. We considered a two-arm, two-stage, parallel group design where population enrichment occurs at the interim analysis by dropping any non-responsive subgroups.

Genetic Counseling Referral Rates in Long-Term Survivors of Triple-Negative Breast Cancer.

Inherited gene mutations (pathogenic variants) cause 10% of breast cancers. pathogenic variants predispose carriers to triple-negative breast cancer (TNBC); around 30% of patients with TNBC carry pathogenic variants. The 2018 NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian recommend genetic counseling referrals for patients with TNBC diagnosed at age ≤60 years.

Determinants of Weight Gain During Adjuvant Endocrine Therapy and Association of Such Weight Gain With Recurrence in Long-term Breast Cancer Survivors.

Background: Weight gain is a negative prognostic factor in breast cancer (BC) patients. The risk factors for weight gain during adjuvant endocrine therapy (ET) and the extent to which such weight gain is associated with disease recurrence remain unclear.

Patients And Methods: We retrospectively identified a cohort of women with a diagnosis of stage I-III, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC from January 1997 to August 2008, who had received initial treatment at the MD Anderson Cancer Center, had completed 5 years of ET, and had remained free of locoregional or distant relapse or contralateral BC for ≥ 5 years after diagnosis.

Medication Regimen Complexity and Low Adherence in Older Community-Dwelling Adults With Substantiated Self-Neglect.

Objective: Determine whether medication regimen complexity predicts medication adherence levels in a sample of community-dwelling adults 65 years and older with Adult Protective Services-substantiated self-neglect.

Methods: A cross-sectional analysis of baseline data ( N = 31 participants) from a pilot intervention to increase medication adherence among the target group was performed. The Medication Regimen Complexity Index (MRCI) and the 8-item Morisky Medication Adherence Scale (MMAS-8)™ were the primary independent and dependent measures, respectively.

Larval infestation in a common Pariah Kite (Boddaert).

This paper describes a case of larval infestation in a common Pariah Kite (Boddaert). Examination on the larvae revealed that the larvae were of the family Sarcophagidae (Diptera).

Outcomes in patients with early-stage breast cancer who underwent a 21-gene expression assay.

Background: Invasive disease-free survival (IDFS) rates are excellent in patients with breast cancer (BC) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), axillary lymph node-negative (LN-) tumors with a 21-gene expression assay recurrence score (RS) of 0 to 10. However, to the authors' knowledge, the outcomes among patients with an RS of 11 to 25 who are treated with endocrine therapy alone are unknown.

Methods: In this retrospective single-institution study, the authors described the characteristics of patients with HR+, HER2-, LN- BC who underwent a 21-gene expression assay.

Mammographic breast density is associated with the development of contralateral breast cancer.

Background: Women with dense mammographic breast density (BD) have a 2-fold increased risk of developing primary breast cancer (BC). The authors hypothesized that dense mammographic BD also is associated with an increased risk of developing contralateral breast cancer (CBC).

Methods: Among female patients treated at The University of Texas MD Anderson Cancer Center for sporadic, AJCC stage I to stage III BC between January 1997 and December 2012, the authors identified patients who had developed metachronous CBC (cases) and selected 1:2 matched controls who did not develop CBC using incidence density sampling, matched on attainted age, year of diagnosis, and hormone receptor status of the first BC.

Location of Receipt of Initial Treatment and Outcomes in Long-Term Breast Cancer Survivors.

Purpose: Cancer outcomes differ depending on where treatment is received. We assessed differences in outcomes in long-term breast cancer survivors at a specialty care hospital by location of their initial treatment.

Methods: We retrospectively examined a cohort of women diagnosed with invasive early-stage breast cancer who did not experience recurrence for at least 5 years after the date of diagnosis and were evaluated at The University of Texas MD Anderson Cancer Center between January 1997 and August 2008.

Five-year all-cause mortality rates across five categories of substantiated elder abuse occurring in the community.

Elder abuse increases the likelihood of early mortality, but little is known regarding which types of abuse may be resulting in the greatest mortality risk. This study included N = 1,670 cases of substantiated elder abuse and estimated the 5-year all-cause mortality for five types of elder abuse (caregiver neglect, physical abuse, emotional abuse, financial exploitation, and polyvictimization). Statistically significant differences in 5-year mortality risks were found between abuse types and across gender.

Comparison of the global statistical test and composite outcome for secondary analyses of multiple coronary heart disease outcomes.

Multiple outcomes (or multiple endpoints), such as mortality and recurrent myocardial infarction, are increasingly common in clinical trials and are often of interest in secondary analyses. Traditionally, a clinical trial protocol is built around a single event as its primary outcome, with several secondary outcomes specified, the analyses for which lack the same level of power. To accommodate all the relevant outcomes and to increase the power of the comparison in trials evaluating the efficacy of treatments for coronary heart disease, investigators often chose to construct a composite outcome.