Syed Zafar

PURPOSE: Insured patients with cancer face high treatment-related, out-of-pocket (OOP) costs and often cannot access financial assistance. We conducted a randomized, controlled trial of Bridge, a patient-facing app designed to identify eligible financial resources for patients. We hypothesized that patients using Bridge would experience greater OOP cost reduction than controls. METHODS: We enrolled patients with cancer who had OOP expenses from January 2018 to March 2019. We randomly assigned patients 1:1 to intervention (Bridge) versus control (financial assistance educational websites). Primary and secondary outcomes were self-reported OOP costs and subjective financial distress 3 months postenrollment. In post hoc analyses, we analyzed application for and receipt of financial assistance at 3 months postenrollment. We used chi-square, Mann-Whitney tests, and logistic regression to compare study arms. RESULTS: We enrolled 200 patients. The median age was 57 years (IQR, 47.0-63.0). Most patients had private insurance (71%), and the median household income was $62,000 in US dollars (USD) (IQR, $36,000-$100,000 [USD]). Substantial missing data precluded assessment of primary and secondary outcomes. In post hoc analyses, patients in the Bridge arm were more likely than controls to both apply for and receive financial assistance. CONCLUSION: We were unable to test our primary outcome because of excessive missing follow-up survey data. In exploratory post hoc analyses, patients who received a financial assistance app were more likely to apply for and receive financial assistance. Ultimately, our study highlights challenges faced in identifying measurable outcomes and retaining participants in a randomized, controlled trial of a mobile app to alleviate financial toxicity.

BACKGROUND Patients with cancer are at risk for both objective and subjective financial distress. Financial distress during treatment is adversely associated with physical and mental well-being. Little is known about whether patients' subjective financial distress changes during the course of their treatment.method This is a cross-sectional study of insured adults with solid tumors on anti-cancer therapy for ≥1 month, surveyed at a referral center and three rural oncology clinics. The goal was to investigate how financial distress varies depending on where patients are in the course of cancer therapy. Financial distress (FD) was assessed via a validated measure; out-of-pocket (OOP) costs were estimated and medical records were reviewed for disease/treatment data. Logistic regression was used to evaluate the potential association between treatment length and financial distress.RESULTS Among 300 participants (86% response rate), median age was 60 years (range 27-91), 52.3% were male, 78.3% had stage IV cancer or metastatic recurrence, 36.7% were retired, and 56% had private insurance. Median income was $60,000/year and median OOP costs including insurance premiums were $592/month. Median FD score (7.4/10, SD 2.5) corresponded to low FD with 16.3% reporting high/overwhelming distress. Treatment duration was not associated with the odds of experiencing high/overwhelming FD in single-predictor (OR = 1.01, CI [.93, 1.09], P = .86) or multiple predictor regression models (OR = .98, CI [.86, 1.12], P = .79). Treatment duration was not correlated with FD as a continuous variable (P = .92).LIMITATIONS This study is limited by its cross-sectional design and generalizability to patients with early-stage cancer and those being treated outside of a major referral center.CONCLUSION Severity of cancer treatment-related financial distress did not correlate with time on treatment, indicating that patients are at risk for FD throughout the treatment continuum. Screening for and addressing financial distress should occur throughout the course of cancer therapy.

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. METHODS: We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. RESULTS: The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group. CONCLUSIONS: Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).

TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT02008383 Sponsor: Duke University Principal Investigator: John H. Strickler IRB Approved: Yes LESSONS LEARNED: Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted. BACKGROUND: The epidermal growth factor receptor (EGFR) antibody panitumumab is active in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), but nearly all patients experience resistance. MET amplification is a driver of panitumumab resistance. Cabozantinib is an inhibitor of multiple kinases, including vascular endothelial growth factor receptor 2 (VEGFR2) and c-MET, and may delay or reverse anti-EGFR resistance. METHODS: In this phase Ib clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of cabozantinib and panitumumab. We then treated an expansion cohort to further describe the tolerability and clinical activity of the RP2D. Eligibility included patients with KRAS WT mCRC (later amended to include only RAS WT mCRC) who had received prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab. RESULTS: Twenty-five patients were enrolled and treated. The MTD/RP2D was cabozantinib 60 mg p.o. daily and panitumumab 6 mg/kg I.V. every 2 weeks. The objective response rate (ORR) was 16%. Median progression free survival (PFS) was 3.7 months (90% confidence interval [CI], 2.3-7.1). Median overall survival (OS) was 12.1 months (90% CI, 7.5-14.3). Five patients (20%) discontinued treatment due to toxicity, and 18 patients (72%) required a dose reduction of cabozantinib. CONCLUSION: The combination of cabozantinib and panitumumab has activity. Dose reductions of cabozantinib improve tolerability.