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BackgroundFinancial costs from cancer treatment are increasingly recognized, but what has historically been underrecognized is the time cost of therapy. We sought to estimate the time burden of anti-cancer drugs approved based on comparisons to best supportive care (BSC), with the assumption that without this drug, a patient could have been treated with observation, home palliative care or hospice services, with minimal time seeking medical care.MethodsWe searched all FDA approvals (2009 - March 2022) for randomized trials that used BSC as a treatment option for an anti-tumor drug in the metastatic setting and abstracted data on treatment related activities. We then estimated time spent on these activities using previously calculated times.ResultsOf the 13 drugs tested against BSC, nine studies demonstrated an improvement in median OS (median 2.1 months). The median monthly time spent for patients in the intervention arm of BSC trials was 15.8 h.ConclusionTime is a valuable resource for people who have cancer, but especially for patients who may have few to no remaining treatment options, and yet, we found that patients can spend up to 16 h in anti-cancer drug related activities per month.Policy summaryBecause survival outcomes are variable for patients being treated in later lines of therapy, time resources are a valuable consideration in the treatment plan.

BackgroundIdentifying ineffective practices that have been used in oncology is important in reducing wasted resources and harm. We sought to examine the prevalence of practices that are being used but have been shown in RCTs to be ineffective (medical reversals) in published oncology studies.MethodsWe cross-sectionally analyzed studies published in three high-impact oncology medical journals (2009-2018). We abstracted data relating to the frequency and characterization of medical reversals.ResultsOf the 64 oncology reversals, medications (44%) represented the most common intervention type (39% were targeted). Fourteen (22%) were funded by pharmaceutical/industry only and 56% were funded by an organization other than pharmaceutical/industry. The median number of years that the practice had been in use prior to the reversal study was 9 years (range 1-50 years).ConclusionHere we show that oncology reversals most often involve the administration of medications, have been practiced for years, and are often identified through studies funded by non-industry organizations.

BackgroundDetermination of the comparative efficacy of one therapy over another for hepatocellular carcinoma (HCC) can be challenging. Application of a recognized value framework to published studies could objectively compare the potential benefit across available therapies.Materials and methodsAn umbrella review of phase III trials for HCC therapies was performed. ASCO Value Framework Net Health Benefit Score version 2 (ASCO-NHB v2) scores, the primary analysis, and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 scores, the secondary analysis, were computed using selected drug registration trials. Both scores were compared between drugs that were Food and Drug Administration (FDA)-approved by 2020 and those that were not.ResultsOf the 22 studies identified, nine were FDA-approved and 13 were not. Across 22 trials, the median overall survival (OS) was 9.2 months (range, 1.9-16.4 months), with a median gain of 0.35 month (range, 2.3-3.3 months). HCC therapies that were FDA-approved showed longer OS (median 10.7 v 7.9 months, P < .01) and higher ASCO NHB scores (+18.4 v -5.7 scores, P < .01). The median gain in OS was 2.2 months in the approved treatments compared with -0.3 months in the unapproved group, with no difference in progression-free survival between the two groups.ConclusionThe nine FDA-approved therapies for HCC have higher mean NHB score than those that were not FDA-approved. The application of ASCO-NHB v2 and other proposed value frameworks could examine data of future therapies for HCC through a patient-oriented approach.

IntroductionKaplan-Meier survival analysis, the cornerstone of evaluating efficacy of oncology drugs in randomised controlled trials (RCTs), assumes censored patients are neither healthier nor sicker than those followed. We sought to examine whether censoring patterns differ between the control and experimental arms in one oncology journal that mandates the reporting of the number of patients censored.MethodsIn this retrospective review, proportion of censoring and study design data were gathered from RCTs published in The Lancet Oncology that reported Kaplan-Meier curves between May 2018 and August 2019. Differential censoring rates were analysed at the 1st, 3rd, 6th, and overall time points in each study. Analysis was stratified by curves reporting progression-free survival (PFS) or overall survival (OS) end-points.ResultsOf the 160 articles reviewed, 29 studies with 51 Kaplan-Meier curves were eligible. In both OS (N = 25) and PFS curves (N = 26), the absolute weighted difference in censoring between the control and experimental arms was initially positive, indicating more censoring in the control arm (first time point OS: 0.32%; PFS: 2.00%). The absolute difference then became negative, indicating more censoring in the experimental arm as time progressed (end-of-study OS: -7.54%; PFS: -9.09%).ConclusionDifferences in censoring between control and experimental arms of cancer RCTs suggest that there could be systematic bias present at various study time points that may influence key results. Further investigation is needed, as possible reasons include study assignment disappointment, inappropriate follow-up length, lack of efficacy, or intolerable toxicity, each predominant at specific time points after randomisation.

Aims patients & methodsIn this retrospective review, we sought to estimate the proportion of patients in the USA with advanced or metastatic cancer who are eligible for and may respond to recommended first-line cytotoxic chemotherapy based on National Comprehensive Cancer Network treatment guidelines.ResultsAmong 609,640 patients, we estimate 479,823 (78.7%, 95% CI: 78.6-78.8%) may be eligible for cytotoxic chemotherapy while 189,159 out of 609,640 patients (31.0%, 95% CI: 30.9-31.1%) may have achieved treatment response. The average objective response rate from these regimens was 48.6% (range 9.2 to 90.6%).ConclusionGiven the large role of cytotoxic agents in cancer, drug development in this space may remain of interest in specific cancer types, and regulatory approval of novel oncology drugs may justify head-to-head comparisons against cytotoxic regimens.

Key Clinical Message: Immunotherapy is considered first line in patients with dMMR metastatic colorectal cancer (CRC). Recent studies have also shown promising results with neoadjuvant immunotherapy in locally advanced CRC. We report a case in which neoadjuvant immunotherapy with pembrolizumab resulted in complete pathologic response at time of resection as well as saved the patient the morbidity associated with a hepatectomy. We also completed a scoping review of the literature which suggests promising tumor responses with treatment in dMMR CRC. Further randomized control trials to determine the magnitude of response and optimal regimen are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment for advanced and metastatic esophagogastric malignancies has historically required time-intensive multi-agent chemotherapy regimens, where patients spend time away from home to engage in therapy administrations and supportive care. With the addition of immunotherapies to the standard of care, the authors completed this study to estimate the time spent in health care across various systemic treatment regimens. The authors estimated the time toxicity, or the days spent in health care facilities, due to cancer diagnosis and treatment with immunotherapy- and chemotherapy-based treatment regimens for esophagogastric cancers. (1) Background: The purpose of this study was to evaluate the time toxicity, or time spent in health care, of immunotherapy- versus chemotherapy-based regimens for metastatic esophageal and gastric cancers. (2) Methods: A literature search was conducted, and 18 phase III clinical trials of immune checkpoint inhibitors were selected for analysis. Health care days were calculated based on the number of days associated with receiving therapy and the adverse events reported in the clinical trials. Both the number of health care days and the median overall survival were compared among chemotherapy-only, immunotherapy-only, and chemo-immunotherapy regimens across this cohort of drug registration trials. (3) Results: The estimated median number of health care days was 37 (range of 7–52) days, or 1.2 (range of 0.2–1.7) months, compared to a median survival of 10.2 months across these 18 studies. For the chemotherapy-only regimens, the median number of health care days was 39 (range of 21–51) days, and for chemo-immunotherapy, it was 39 (range of 30–52) days. The immunotherapy-only regimens had fewer days, a median of 28 (range of 24–41), p < 0.05, compared to the other two arms. (4) Conclusions: The chemo-immunotherapy regimens did not add time toxicity compared to chemotherapy alone. The immunotherapy-only regimens had lower time toxicity compared to chemotherapy alone. In the setting of decreased time toxicity and improved overall survival, further development of immunotherapy-based regimens could improve outcomes in advanced esophageal and gastric cancers. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant treatment with nab‐paclitaxel and gemcitabine for potentially operable pancreatic adenocarcinoma has not been well studied in a prospective interventional trial and could down‐stage tumors to achieve negative surgical margins. Methods: A single‐arm, open‐label phase 2 trial (NCT02427841) enrolled patients with pancreatic adenocarcinoma deemed to be borderline resectable or clinically node‐positive from March 17, 2016 to October 5, 2019. Patients received preoperative gemcitabine 1000 mg/m2 and nab‐paclitaxel 125 mg/m2 on Days 1, 8, 15, every 28 days for two cycles followed by chemoradiation with 50.4 Gy intensity‐modulated radiation over 28 fractions with concurrent fluoropyrimidine chemotherapy. After definitive resection, patients received four additional cycles of gemcitabine and nab‐paclitaxel. The primary endpoint was R0 resection rate. Other endpoints included treatment completion rate, resection rate, radiographic response rate, survival, and adverse events. Results: Nineteen patients were enrolled, with the majority having head of pancreas primary tumors, both arterial and venous vasculature involvement, and clinically positive nodes on imaging. Among them, 11 (58%) underwent definitive resection and eight of 19 (42%) achieved R0 resection. Disease progression and functional decline were primary reasons for deferring surgical resection after neoadjuvant treatment. Pathologic near‐complete response was observed in two of 11 (18%) resection specimens. Among the 19 patients, the 12‐month progression‐free survival was 58%, and 12‐month overall survival was 79%. Common adverse events were alopecia, nausea, vomiting, fatigue, myalgia, peripheral neuropathy, rash, and neutropenia. Conclusion: Gemcitabine and nab‐paclitaxel followed by long‐course chemoradiation represents a feasible neoadjuvant treatment strategy for borderline resectable or node‐positive pancreatic cancer. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma is a lethal malignancy of the biliary epithelium that can arise anywhere along the biliary tract. Surgical resection confers the greatest likelihood of long‐term survivability. However, its insidious onset, difficult diagnostics, and resultant advanced presentation render the majority of patients unresectable, highlighting the importance of early detection with novel biomarkers. Developing liver‐directed therapies and emerging targeted therapeutics may offer improved survivability for patients with unresectable or advanced disease. In this article, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options. In this study, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options. [ABSTRACT FROM AUTHOR]