Phase II study of neratinib in older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer.

OBJECTIVE: The tolerability and efficacy of targeted therapy in older adults with cancer has not been adequately studied. Neratinib is a novel HER1, HER2, HER4 tyrosine kinase inhibitor that has recently been granted FDA approval for treatment of breast cancer. The major toxicity of neratinib is diarrhea, which affects up to 90% of patients. This phase II trial evaluates the safety and tolerability of neratinib in adults ≥60. METHODS: Patients aged 60 or older with histologically proven metastatic breast cancer and HER2 amplification (defined by ASCO/CAP guideline) or HER2/HER3 activating mutation were enrolled to receive neratinib at 240 mg daily in 28-day cycles. The association between tolerability, defined as dose reduction and number of completed courses, and log2 Cancer and Aging Research Group (CARG) toxicity risk score was assessed using a Student's t-test and linear regression, respectively. Response rate, progression free survival, and overall survival were also evaluated. RESULTS: 25 patients were enrolled with median age of 66 (range 60-79). Seventy-six percent of patients were white, 16% Asian, and 8% African-American. Seventy-six percent were patients with hormone receptor (HR) positive metastatic breast cancer (MBC) and 24% were patients with HR negative MBC. Median number of prior lines of metastatic therapy were 3 (range 0-11). 20/25 (80%) had worst grade toxicities ≥2. A total of 9/25 (36%) had grade 3 toxicities including 5/20 (20%) diarrhea, 2/20 (8%) vomiting, and 2/20 (8%) abdominal pain. There were no grade 4 or 5 toxicities. A total of 9/25 (36%) had dose reduction, and 2/25 (8%) discontinued therapy due to toxicity. The association between dose reductions and CARG toxicity score reached borderline statistical significance suggesting a trend with participants with higher CARG toxicity risk scores being more likely to require a dose modification (p = 0.054). 1/25 (4%) had a partial response, 11/25 (44%) had stable disease, 12/25 (48%) had progression of disease, and 1/25 (4%) was not assessed. Median progression free survival (PFS) was 2.6 months (95% CI [2.56-5.26]), and median overall survival (OS) was 17.4 months (95% CI [10.3, NA]). CONCLUSIONS: Neratinib was safe in this population of older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer (BC). Higher CARG toxicity risk score may be associated with greater need for dose adjustments. Future studies are needed to confirm this finding.

Implementing Lung Cancer Screening and Prevention in Academic Centers, Affiliated Network Offices and Collaborating Care Sites.

Lung cancer is one of the deadliest and yet largely preventable neoplasms. Smoking cessation and lung cancer screening are effective yet underutilized lung cancer interventions. City of Hope Medical Center, a National Cancer Institute (NCI)- designated comprehensive cancer center, has 27 community cancer centers and has prioritized tobacco control and lung cancer screening throughout its network. Despite challenges, we are implementing and monitoring the City of Hope Tobacco Control Initiative including 1) a Planning and Implementation Committee; 2) integration of IT, e.g., medical records and clinician notification/prompts to facilitate screening, cessation referral, and digital health, e.g., telehealth and social media; 3) clinician training and endorsing national guidelines; 4) providing clinical champions at all sites for site leadership; 5) Coverage and Payment reform and aids to facilitate patient access and reduce cost barriers; 6) increasing tobacco exposure screening for all patients; 7) smoking cessation intervention and evaluation-patient-centered recommendations for smoking cessation for all current and recent quitters along with including QuitLine referral for current smokers and smoking care-givers; and 8) establishing a Tobacco Registry for advancing science and discoveries including team science for basic, translation and clinical studies. These strategies are intended to inform screening, prevention and treatment research and patient-centered care.

A phase 3 trial of armodafinil for the treatment of cancer-related fatigue for patients with multiple myeloma.

PURPOSE: Fatigue is a common problem among multiple myeloma (MM) patients. Armodafinil is a drug known to promote wakefulness, which is related to modafinil, a compound that improves fatigue in some cancer patients treated with chemotherapeutic agents. We investigated whether armodafinil could reduce cancer-related fatigue in MM patients. METHODS: This double-blind, placebo-controlled phase 3 trial evaluated the efficacy of armodafinil in MM patients with evidence of moderate fatigue. Patients were randomized to one of two arms: treatment-only, with armodafinil given at 150 mg/daily for 56 days, or placebo-first, with placebo given on days 1-28, followed by armodafinil administered at 150 mg daily on days 29-56. Fatigue was measured on days 1 (pre-dose: baseline), 15, 28, 43, and 56 using seven separate assessments, including four patient-reported outcomes of fatigue and related quality of life measures, as well as three objective measures of cognitive function. RESULTS: Overall toxicities were similar between treatment groups. No significant differences were observed between the placebo-first and the treatment-only arms after 28 days. Treatment with armodafinil for 28 additional days did not produce responses. Both placebo-first and treatment-only patients showed similar significant improvements in three patient-reported measures and one objective task at day 28 compared to baseline. Placebo-first patients improved on eight additional measures (one patient-reported measure, six subscales, and one objective task), suggesting a strong placebo effect in this patient population. CONCLUSIONS: Evaluation and treatment of cancer-related fatigue continues to be challenging; a clear definition of this symptom and better assessment tools are needed.

Prognostic factors and jaw and renal complications among multiple myeloma patients treated with zoledronic acid.

Few studies have evaluated prognostic factors among patients with multiple myeloma (MM) since new therapies have become available. Monthly zoledronic acid (ZOL) has been incorporated into many treatment regimens to reduce skeletal-related events (SREs), but outcomes among patients receiving this bisphosphonate have not been well-defined. The aim of this retrospective study was to determine baseline and on-treatment prognostic factors in these patients. Data were collected from the date of diagnosis on 300 consecutive MM patients treated with ZOL. Median duration of ZOL was 18 months (range 1-121 months). The skeletal morbidity rate was 0.116 events per patient year. Five-year overall survival (OS) was 69%. Risk factors for shortened OS included SREs, increased serum creatinine, and International Staging System (ISS) Stage II or III. Thirty-four (11%) patients showed worsening renal function. In 28 of these patients, ZOL was discontinued and restarted in half of these patients following a brief delay. Only 5 of the 34 patients showed worsening of their renal function. Fourteen patients (4.7%) developed osteonecrosis of the jaw (ONJ). All patients with ONJ are in remission or with stable disease except one patient who died of a myocardial infarction while in remission. Only two patients showed some worsening of ONJ despite of ongoing monthly ZOL. Overall, these results suggest that skeletal complications are an important prognostic factor for MM. Although ONJ and renal deterioration may infrequently occur with ZOL, most patients do not experience worsening of these conditions with ongoing treatment with this bisphosphonate.