AbstractBackground.The loss of muscle mass, known as sarcopenia, is a natural process of aging that is associated with adverse health outcomes regardless of age. Because cancer is a disease of aging, interest in sarcopenia and its potential impact in multiple cancer populations has increased significantly. Bioelectrical impedance analysis (BIA) is a guideline‐accepted method for sarcopenia detection. This systematic review assesses the literature pertaining to BIA use in the detection of sarcopenia in adults with cancer.Materials and Methods.In this systematic review, a search of the literature for randomized controlled trials and observational studies was conducted using MEDLINE, Cochrane CENTRAL, and EMBASE, through July 15, 2019. The study is registered at Prospero (CRD 42019130707). For study inclusion, patients had to be aged 18 years or older and diagnosed with solid or hematological neoplasia, and BIA had to be used to detect sarcopenia.Results.Through our search strategy, 5,045 articles were identified, of which 24 studies were selected for inclusion in the review (total number of 3,607 patients). In five studies, BIA was rated comparable to axial computed tomography (CT) scan, calf circumference, or grip strength for sarcopenia screening. In 14 studies, BIA‐identified sarcopenia was associated with adverse clinical outcomes.Conclusion.BIA is an accurate method for detecting sarcopenia in adults with cancer prior to treatment and is a viable alternative to CT, dual‐energy x‐ray absorptiometry, and magnetic resonance imaging in oncology clinical practice.Implications for Practice.Bioelectrical impedance analysis (BIA) is an attractive method for identifying sarcopenic patients in clinical practice because it provides an affordable, noninvasive test that can be completed within a few minutes during a clinic visit. BIA does not require highly skilled personnel, and results are immediately available. This systematic review summarizes the literature pertaining to BIA assessment of sarcopenia in adults with cancer, with a focus on its use in diverse cancer populations.
AbstractBackground.Somatostatin analogs (SSAs) are the mainstay of neuroendocrine tumor (NET) treatment. Biliary stone disease is reported as a common side effect of SSAs, with a frequency ranging from 10% to 63%. Studies on SSA‐treated patients for acromegaly report an increased incidence of biliary stone disease compared with the general population, whereas data on patients with NETs are few. Guidelines are based on weak evidence, thus resulting in conflicting recommendations. The aim of the study is to evaluate biliary stone disease incidence, complications, and risk factors in a large population of SSA‐treated patients with NETs.Materials and Methods.A retrospective analysis of a prospectively collected database was performed. Patients with a diagnosis of NET in seven dedicated centers from 1995 to 2017 were included at the time of SSA start.Results.A total of 754 SSA‐treated patients were evaluated. Patients with history of cholecystectomy or with known biliary stone disease were excluded; 478 patients were included. Among them, 118 patients (24.7%) received prophylactic ursodeoxycholic acid (UDCA). During the study period, 129 patients (27.0%) developed biliary stone disease; of them, 36 (27.9%) developed biliary complications. On multivariate analysis, primary gastrointestinal (GI)‐NET (hazard ratio [HR] 1.76) and related surgery (HR 1.58) were independent risk factors for biliary stone disease.Conclusion.We report a high incidence of biliary stone disease particularly in GI‐NET or GI surgery. UDCA prophylaxis does not seem to have a protective role. Our data suggest that all patients with primary GI‐NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy; no conclusion could be drawn on the indication of prophylactic cholecystectomy in patients with primary pancreatic or thoracic NET for whom abdominal surgery is not planned.Implications for Practice.The results of this study confirm an increased rate of gallstones development and related complications in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs (SSAs). NETs of the gastrointestinal (GI) tract and related surgery are independent risk factors for biliary stone disease development. Therefore, all patients with primary GI‐NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy. Data on other subgroups are not exhaustive, and management also evaluating additional clinical features (life expectancy, surgical and anesthesiological risks) should be considered. Prophylactic treatment with ursodeoxycholic acid does not seem to be a protective factor for SSA‐related biliary stone disease.
AbstractBackground.Somatic alterations in circulating tumor DNA (ctDNA) may be associated with treatment response or prognosis in prostate cancer (PCa). The goal was to characterize androgen receptor gene (AR) amplifications and mutations detected in ctDNA from patients with PCa and to further understand the somatic genetic heterogeneity of advanced prostate cancer.Patients and Methods.This study included a heterogeneous group of 892 patients with advanced PCa (predominantly castrate‐resistant prostate cancer) with AR alterations detected in ctDNA that underwent next‐generation sequencing of 54 to 73 genes via Guardant360 testing (Guardant Health, Inc., Redwood City, CA). Distribution and summary of AR alterations detected, the association of AR alterations with other genes, and a pathway analysis are reported.Results.The median absolute plasma copy number of AR amplifications was 3.3 (range, 1.2–165.2). Many patients had multiple AR mutations; a total of 112 unique mutations were identified in AR, including L702H (25%), T878A (14%), H875Y (11%), W742C (8%), W742L (4%), F877L (2%), and T878S (2%). Other ctDNA gene alterations in the Guardant assays included TP53 (50%), MYC (34%), BRAF (32%), PIK3CA (29%), MET (25%), CDK6 (26%), EGFR (24%), FGFR1 (21%), and APC (12%). Many of these non‐AR alterations are not tissue verified in other studies. AR amplification cosegregated with alterations in MYC (p < .001), BRAF (p < .001), PIK3CA (p < .001), MET (p < .001), CDK6 (p < .001), EGFR (p < .001), FGFR1 (p = .391), and more. Alterations in APC were significantly associated with mutations in AR (p < .001).Conclusion.Several AR alterations and concomitant non‐AR alterations that associate with drug resistance were detected. These findings provide additional insights into the heterogeneity of advanced prostate cancer.Implications for Practice.The goal was to characterize androgen receptor gene (AR) amplifications and mutations detected in circulating tumor DNA (ctDNA) from patients with prostate cancer in relation to non‐AR gene alterations detected in the ctDNA landscape. The study included 892 patients with prostate cancer with AR alterations in ctDNA. AR alterations were significantly associated with other gene alterations detected in ctDNA. The common AR mutations found are linked to resistance to abiraterone, enzalutamide, or bicalutamide. Characterization of the circulating AR landscape and gene alterations provides potential additional insight into the somatic genetic heterogeneity of advanced prostate cancer.
AbstractBackground.Anti‐programmed cell death 1 antibody is a standard therapy for advanced non‐small cell lung cancer (NSCLC). However, immune‐related adverse events (irAEs), such as skin reactions, are frequently observed. Although skin reactions are associated with clinical efficacy in melanoma, this association in advanced NSCLC and predictors of irAEs remain unclear. Accordingly, this study identified potential correlations of skin reactions with clinical efficacy and clinical predictors of development of skin reactions.Subjects, Materials, and Methods.We retrospectively surveyed patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital (n = 155) during January 2016 to April 2018. Treatment efficacy was evaluated in patients with and without skin reactions, and associated predictive markers were determined. A 6‐week landmark analysis was conducted to assess the clinical benefit of early skin reactions.Results.Skin reactions were observed in 51 patients with a median time to onset of 6.4 weeks. The overall response rate (ORR) was significantly higher in patients with skin reactions (57% vs. 19%, p < .001). Median progression‐free survival (PFS) durations of 12.9 and 3.5 months and overall survival durations of not reached and 11.4 months were observed in patients with and without skin reactions, respectively. In the 6‐week landmark analysis, the ORR was significantly higher in patients with skin reactions, and skin reactions were significantly associated with increased PFS. A multivariate analysis identified pre‐existing rheumatoid factor (RF) as an independent predictor of skin reactions.Conclusion.Skin reactions appeared beneficial in patients treated with nivolumab/pembrolizumab for advanced NSCLC and could be predicted by pre‐existing RF. Further large‐scale validations studies are warranted.Implications for Practice.This single‐institutional medical record review that included 155 patients with advanced non‐small cell lung cancer who were treated with nivolumab or pembrolizumab monotherapy revealed that overall response rate and progression‐free survival were significantly better in patients with skin reactions. Pre‐existing rheumatoid factor was an independent predictor of skin reactions.
AbstractBackground.Delirium, a neuropsychiatric syndrome that occurs throughout medical illness trajectories, is frequently misdiagnosed. The Memorial Delirium Assessment Scale (MDAS) is a commonly used tool in palliative care (PC) settings. Our objective was to establish and validate the Memorial Delirium Assessment Scale‐Thai version (MDAS‐T) in PC patients.Materials and Methods.The MDAS was translated into Thai. Content validity, inter‐rater reliability, and internal consistency were explored. The construct validity of the MDAS‐T was analyzed using exploratory factor analysis. Instrument testing of the MDAS‐T, the Thai version of the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU‐T), and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition as the gold standard was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff score. The duration of each assessment was recorded.Results.The study enrolled 194 patients. The content validity index was 0.97. The intraclass correlation coefficient and Cronbach's α coefficient were 0.98 and 0.96, respectively. A principal component analysis indicated a homogeneous, one‐factor structure. The area under the ROC curve was 0.96 (95% confidence interval [CI], 0.93–0.99). The best combination of sensitivity and specificity (95% CI) of the MDAS‐T were 0.92 (0.85–0.96) and 0.90 (0.82–0.94), respectively, with a cutoff score of 9, whereas the CAM‐ICU‐T yielded 0.58 (0.48–0.67) and 0.98 (0.93–0.99), respectively. The median MDAS‐T assessment time was 5 minutes.Conclusion.This study established and validated the MDAS‐T as a good and feasible tool for delirium screening and severity rating in PC settings.Implications for Practice.Delirium is prevalent in palliative care (PC) settings and causes distress to patients and families, thereby making delirium screening necessary. This study found that the MDAS‐T is a highly objective and feasible test for delirium screening and severity monitoring in PC settings and can greatly improve the quality of care for this population.
AbstractBackground.Biliary tract cancers (BTCs) are highly fatal malignancies that make up less than 1% of all cancers. BTC is often diagnosed at an unresectable stage; surgical resection remains the only definitive treatment. Brain metastases (BMs) from BTC are extremely rare, and few studies on patients with BMs from BTC exist. The aim of this study was to identify clinical characteristics associated with poor prognosis for patients with BMs from BTC.Materials and Methods.We performed a retrospective review of electronic medical records for patients with BMs from BTC managed at Mount Sinai Hospital from 2000 to 2017. Data on patient characteristics, magnetic resonance imaging findings, treatment regimens, and clinical outcomes were analyzed.Results.We identified 1,910 patients with BTC. Nine patients developed BMs, with an incidence of 0.47%. Of these nine patients, six had intrahepatic cholangiocarcinoma, two had extrahepatic cholangiocarcinoma, and one had gallbladder cancer. Six (66.7%) patients had one BM, one (11.1%) patient had two BMs, and two (22.2%) patients had three or more BMs. Four (44.4%) patients underwent BM resection, and seven (77.8%) received BM radiation. Median overall survival from time of BM diagnosis was 3.8 months (95% confidence interval 0.1–16.9).Conclusion.Development of BMs from BTC is rare; however, prognosis is less than 4 months. BM diagnosis can occur within 2 years of primary diagnosis. As targeted therapeutics emerge, future studies ought to focus on identifying genomic BM markers associated with BTC subtypes.Implications for Practice.In the largest retrospective study of biliary tract cancer brain metastases, the clinical presentation and outcomes are reported of nine patients with an extremely rare clinical entity. The genomic literature and potential therapeutic targets for these patients with limited treatment options is comprehensively and exhaustively discussed.
AbstractOncologic treatment is being revolutionized by a burgeoning number of immune checkpoint inhibitors (ICPis). To date, seven ICPis have received Food and Drug Administration approval, targeting cytotoxic T‐lymphocyte antigen, programmed cell death, or programmed cell death ligand. Adverse events associated with checkpoint inhibition have been described in the literature. Guidelines exist for the most common of these, but as the use of ICPis becomes more common, the number of patients presenting with rare events will increase. This article reviews the diagnosis and management of rare ocular, hematological, luminal gastrointestinal, and rheumatological toxicities arising from ICPi treatment.Key Points.As the use of immune checkpoint inhibitors (ICPis) becomes more common, the number of rare immune‐related adverse events (irAEs) will increase. A high level of suspicion is required to identify and treat these toxicities.Although it can be difficult to definitively attribute rare irAEs to ICPis, a temporal and mechanistic relationship and the absence of other etiologies should make the treating physician suspicious for a rare irAE.Certain rare irAEs, such as celiac disease, do not require treatment with glucocorticoids. Thus, differentiating this irAE from other gastrointestinal irAEs has important implications for treatment.
AbstractThymomas comprise a group of rare epithelial neoplasms of the anterior mediastinum. Whereas localized disease carries a favorable prognosis, the majority of patients with metastatic thymomas experience progression or recurrence over a 10‐year period. Although targeted therapies have become standard of care in many malignancies, no clinically actionable mutations have consistently been identified in metastatic thymomas. Here, we describe a patient with an aggressive thymoma complicated by extensive pleural metastases. Over a 16‐year period, she progressed on multiple treatment regimens. To identify additional treatment options, tissue from a pleural metastasis was sent for next‐generation sequencing, revealing mutations in BRCA2, tyrosine kinase 2, and SET domain containing 2. Based on supporting evidence for poly (ADP‐ribose) polymerase (PARP) inhibition in other BRCA‐mutated tumors, the patient was started on the PARP inhibitor olaparib. She derived significant clinical benefit from treatment, with imaging showing overall stabilization of her disease. Here, we review the genotyping results of her tumor and discuss the functional and clinical significance of the mutations in her cancer as well as implications for managing patients with advanced BRCA‐mutant thymomas.Key Points.Targeted therapy has yet to enter the standard clinical management of metastatic thymomas.Patients with BRCA2‐mutant thymomas may benefit from poly (ADP‐ribose) polymerase inhibition.
AbstractBackground.Health‐related quality of life (HRQoL) has been shown to be a prognostic factor for cancer survival in randomized clinical trials and observational “real‐world” cohort studies; however, it remains unclear which HRQoL domains are the best prognosticators. The primary aims of this population‐based, observational study were to (a) investigate the association between the novel European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core30 (QLQ‐C30) summary score and all‐cause mortality, adjusting for the more traditional sociodemographic and clinical prognostic factors; and (b) compare the prognostic value of the QLQ‐C30 summary score with the global quality of life (QoL) and physical functioning scales of the QLQ‐C30.Materials and Methods.Between 2008 and 2015, patients with cancer (12 tumor types) were invited to participate in PROFILES disease‐specific registry studies (response rate, 69%). In this secondary analysis of 6,895 patients, multivariate Cox proportional hazard regression models were used to investigate the association between the QLQ‐C30 scores and all‐cause mortality.Results.In the overall Cox regression model including sociodemographic and clinical variables, the QLQ‐C30 summary score was associated significantly with all‐cause mortality (hazard ratio [HR], 0.77; 99% confidence interval [CI], 0.71–0.82). In stratified analyses, significant associations between the summary score and all‐cause mortality were observed for colon, rectal, and prostate cancer, non‐Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma. The QLQ‐C30 summary score had a stronger association with all‐cause mortality than the global QoL scale (HR, 0.82; 99% CI, 0.77–0.86) or the physical functioning scale (HR, 0.81; 95% CI, 0.77–0.85).Conclusion.In a real‐world setting, the QLQ‐C30 summary score has a strong prognostic value for overall survival for a number of populations of patients with cancer above and beyond that provided by clinical and sociodemographic variables. The QLQ‐C30 summary score appears to have more prognostic value than the global QoL, physical functioning, or any other scale within the QLQ‐C30.Implications for Practice.The finding that health‐related quality of life provides distinct prognostic information beyond known sociodemographic and clinical measures, not only around cancer diagnosis (baseline) but also at follow‐up, has implications for clinical practice. Implementation of cancer survivorship monitoring systems for ongoing surveillance may improve post‐treatment rehabilitation that leads to better outcomes.
AbstractBackground.Venous thromboembolism (VTE) is a frequent complication in patients with cancer and causes considerable morbidity and mortality. The risk of VTE is higher in patients with pancreatic cancer and is often associated with treatment delays or interruptions. Recently, the ONKOTEV score was proposed as a VTE risk predictor model for patients with cancer, but its validation is still ongoing.Patients and Methods.We conducted a retrospective study to determine the incidence of VTE and to evaluate the ONKOTEV score as a VTE predictive tool in a population of patients with pancreatic cancer.Results.Between February 2012 and May 2017, 165 patients were included in the study. The median age was 73 years, 45.5% of patients were female, and 55.8% had stage IV disease. Fifty‐one patients had a VTE (30.9%); 23.5% had pulmonary embolism, 25.5% had deep venous thrombosis, and 51.0% had visceral VTE (VsT). At a median follow‐up time of 6.3 months, cumulative incidence of VTE was less than 10% for ONKOTEV scores 0 or 1 and approximately 40% and 70% for scores 2 and ≥3, respectively.Conclusion.The high VTE incidence observed in this study is consistent with prior reports. Patients at high risk for VTE with no increase in hemorrhagic risk should be considered for primary thromboprophylaxis. The ONKOTEV score may stratify VTE risk in patients with pancreatic cancer, with ONKOTEV score ≥2 being associated with a higher VTE occurrence.Implications for Practice.Venous thromboembolism (VTE) is a frequent complication of patients with pancreatic cancer and causes considerable morbidity, treatment delays or interruptions, and mortality. Thromboprophylaxis is not used routinely in ambulatory patients. Tools to stratify the risk of VTE are important to help select patients who may benefit from thromboprophylaxis. Recently, the ONKOTEV score was proposed as a VTE risk predictor model for patients with cancer, but its validation is still ongoing. In this patient series, ONKOTEV score ≥2 was associated with high VTE occurrence and may stratify VTE risk in patients with pancreatic cancer, suggesting that ONKOTEV can be considered to select patients with pancreatic cancer for primary thromboprophylaxis.
AbstractLessons Learned.Alectinib confers a pronounced survival benefit in patients with ALK rearrangement‐positive non‐small cell lung cancer and a poor performance status.Survival benefit of alectinib for patients with a poor performance status was consistent regardless of the presence of central nervous system metastases.Background.We previously reported a marked objective response rate (ORR) and safety for alectinib treatment in patients with ALK rearrangement‐positive non‐small cell lung cancer (NSCLC) and a poor performance status (PS) in the Lung Oncology Group in Kyushu (LOGiK) 1401 study. It remained unclear, however, whether alectinib might also confer a long‐term survival benefit in such patients.Methods.Eighteen patients with ALK rearrangement‐positive advanced NSCLC and a PS of 2, 3, or 4 (n = 12, 5, and 1, respectively) were enrolled in LOGiK1401 between September 2014 and December 2015 and received alectinib. We have now updated the survival data for the study.Results.The median follow‐up time for all patients was 27.3 months. The median progression‐free survival (PFS) was 16.2 months (95% confidence interval [CI], 7.1–30.8 months), and the median survival time (MST) and the 3‐year overall survival rate were 30.3 months (95% CI, 11.5 months to not reached) and 43.8% (95% CI, 20.8–64.7%), respectively. This survival benefit was similarly manifest in patients with a PS of 2 (MST, 20.5 months) and those with a PS of ≥3 (MST, not reached). PFS did not differ between patients with or without central nervous system (CNS) metastases at baseline (median of 17.5 and 16.2 months, respectively, p = .886).Conclusion.Alectinib showed a pronounced survival benefit for patients with ALK rearrangement‐positive NSCLC and a poor PS regardless of the presence of CNS metastases, a patient population for which chemotherapy is not indicated.
AbstractImmune checkpoint inhibitors have proven to be effective for various advanced neoplasia. Immune‐related adverse events (irAEs) as a result of increased T cell activation are unique and potentially life‐threating toxicities associated with the use of immune checkpoint inhibitors. Multiple endocrine irAEs, including primary hyperthyroidism and hypothyroidism, thyroiditis, primary adrenal insufficiency, type 1 diabetes mellitus, and hypophysitis, have been reported with the use of various immune checkpoint inhibitors. In some cases, these irAEs can lead to discontinuation of treatment. Here we propose for the general oncologist algorithms for managing endocrine irAEs to aid in the clinical care of patients receiving immunotherapy.Key Points.There is a relative high risk of endocrine immune‐related adverse events (irAEs) during therapy with checkpoint inhibitors, particularly when combination therapy is implemented.Patients treated with anti‐CTLA‐4 antibodies have an increased risk of hypophysitis, whereas patients treated with anti‐PD‐1/PD‐L1 antibodies have a higher risk of primary thyroid dysfunction.Rarely, patients develop T1DM and central diabetes insipidus, and hypoparathyroidism is a rare occurrence.A growing clinical understanding of endocrine irAEs has led to effective treatment strategies with hormone replacement.
AbstractManagement of melanoma has been revolutionized by the use of immune checkpoint inhibitors. Immune system changes associated with aging may affect the efficacy of immune‐based therapies. Using the National Cancer Database, we evaluated the impact of age on the receipt and efficacy of modern immunotherapies in patients with metastatic melanoma. We identified 11,944 patients from 2011–2015, of whom 25% received immunotherapy. Older (≥60 years), compared with younger, patients were less likely to receive immunotherapy (odds ratio, 0.69; 95% confidence interval [CI], 0.61–0.78; p < .001). Immunotherapy was associated with a survival benefit in both younger and older patients (<60 years: hazard ratio [HR], 0.64; 95% CI, 0.57–0.72; p < .001; ≥60 years: HR, 0.55; 95% CI, 0.50–0.60; p < .001). Importantly, there was a statistically significant interaction between age and survival with immunotherapy, where a greater benefit was observed for older patients (pinteraction = 0.013). Further work studying the age‐related response to immunotherapy is warranted.
AbstractBackground.The Institute of Medicine recommends that survivorship care plans (SCPs) be included in cancer survivorship care. Our meta‐analysis compares patient‐reported outcomes between SCP and no SCP (control) conditions for cancer survivors. Our systematic review examines the feasibility of implementing SCPs from survivors' and health care professionals' perspectives and the impact of SCPs on health care professionals’ knowledge and survivorship care provision.Methods.We searched seven online databases (inception to April 22, 2018) for articles assessing SCP feasibility and health care professional outcomes. Randomized controlled trials comparing patient‐reported outcomes for SCP recipients versus controls were eligible for the meta‐analysis. We performed random‐effects meta‐analyses using pooled standardized mean differences for each patient‐reported outcome.Results.Eight articles were eligible for the meta‐analysis (n = 1,286 survivors) and 50 for the systematic review (n = 18,949 survivors; n = 3,739 health care professionals). There were no significant differences between SCP recipients and controls at 6 months postintervention on self‐reported cancer and survivorship knowledge, physical functioning, satisfaction with information provision, or self‐efficacy or at 12 months on anxiety, cancer‐specific distress, depression, or satisfaction with follow‐up care. SCPs appear to be acceptable and potentially improve survivors’ adherence to medical recommendations and health care professionals’ knowledge of survivorship care and late effects.Conclusion.SCPs appear feasible but do not improve survivors’ patient‐reported outcomes. Research should ascertain whether this is due to SCP ineffectiveness, implementation issues, or inappropriate research design of comparative effectiveness studies.Implications for Practice.Several organizations recommend that cancer survivors receive a survivorship care plan (SCP) after their cancer treatment; however, the impact of SCPs on cancer survivors and health care professionals is unclear. This systematic review suggests that although SCPs appear to be feasible and may improve health care professionals’ knowledge of late effects and survivorship care, there is no evidence that SCPs affect cancer survivors’ patient‐reported outcomes. In order to justify the ongoing implementation of SCPs, additional research should evaluate SCP implementation and the research design of comparative effectiveness studies. Discussion may also be needed regarding the possibility that SCPs are fundamentally ineffective.
AbstractBackground.In the phase III MONARCH 2 study (NCT02107703), abemaciclib plus fulvestrant significantly improved progression‐free survival (PFS) versus placebo plus fulvestrant in patients with hormone receptor‐positive (HR+), HER2‐negative advanced breast cancer (ABC). This study assessed patient‐reported pain, global health‐related quality of life (HRQoL), functioning, and symptoms.Materials and Methods.Abemaciclib or placebo (150 p.o. mg twice daily) plus fulvestrant (500 mg, per label) were randomly assigned (2:1). The modified Brief Pain Inventory, Short Form (mBPI‐sf); European Organization for Research and Treatment of Cancer (EORTC) QoL Core 30 (QLQ‐C30); and Breast Cancer Questionnaire (QLQ‐BR23) assessed outcomes. Data were collected at baseline, cycle 2, every two cycles 3–13, thereafter at every three cycles, and 30 days postdiscontinuation. Longitudinal mixed regression and Cox proportional hazards models assessed postbaseline change and time to sustained deterioration (TTSD) by study arm.Results.On‐treatment HRQoL scores were consistently maintained from baseline and similar between arms. Patients in the abemaciclib arm (n = 446) experienced a 4.9‐month delay in pain deterioration (mBPI‐sf), compared with the control arm (n = 223), and significantly greater TTSD on the mBPI‐sf and analgesic use (hazard ratio, 0.76; 95% CI, 0.59–0.98) and QLQ‐C30 pain item (hazard ratio, 0.62; 95% CI, 0.48–0.79). TTSD for functioning and most symptoms significantly favored the abemaciclib arm, including fatigue, nausea and vomiting, and cognitive and social functioning. Only diarrhea significantly favored the control arm (hazard ratio, 1.60; 95% CI, 1.20–2.10).Conclusion.HRQoL was maintained on abemaciclib plus fulvestrant. Alongside superior PFS and manageable safety profile, results support treatment with abemaciclib plus fulvestrant in a population of patients with endocrine‐resistant HR+, HER2‐negative ABC.Implications for Practice.In MONARCH 2, abemaciclib plus fulvestrant demonstrated superior efficacy and a manageable safety profile for patients with in hormone receptor‐positive (HR+), HER2‐negative (−) advanced breast cancer (ABC). Impact on health‐related quality of life (HRQoL) is important to consider, given the palliative nature of ABC treatment. In this study, abemaciclib plus fulvestrant, compared with placebo plus fulvestrant, significantly delayed sustained deterioration of pain and other patient‐reported symptoms (including fatigue, nausea, vomiting), and social and cognitive functioning. Combined with demonstrated clinical benefit and tolerability, the stabilization of patient‐reported symptoms and HRQoL further supports abemaciclib plus fulvestrant as a desirable treatment option in endocrine resistant, HR+, HER2− ABC.
AbstractLessons Learned.Updated survival data for a phase I/II study of carboplatin plus nab‐paclitaxel and concurrent radiotherapy were collected.In the group of 58 patients who were enrolled at 14 institutions in Japan, the median overall survival was not reached and the 2‐year overall survival rate was 66.1% (95% confidence interval, 52.1%–76.8%).Results reveal encouraging feasibility and activity for this regimen.Background.We report the updated survival data for a phase I/II study of carboplatin plus nab‐paclitaxel (nab‐P/C) and concurrent radiotherapy (CRT) in patients with locally advanced non‐small cell lung cancer (NSCLC).Methods.Individuals between 20 and 74 years of age with unresectable NSCLC of stage IIIA or IIIB and a performance status of 0 or 1 were eligible for the study. Patients received weekly nab‐paclitaxel at 50 mg/m2 for 6 weeks together with weekly carboplatin at an area under the curve (AUC) of 2 mg/ml/min and concurrent radiotherapy with 60 Gy in 30 fractions. This concurrent phase was followed by a consolidation phase consisting of two 3‐week cycles of nab‐paclitaxel (100 mg/m2 on days 1, 8, and 15) plus carboplatin (AUC of 6 on day 1). After the treatment, patients were observed off therapy. The primary endpoint of the phase II part of the study was progression‐free survival (PFS).Results.Between October 2014 and November 2016, 58 patients were enrolled at 14 institutions in Japan, with 56 of these individuals being evaluable for treatment efficacy and safety. At the median follow‐up time of 26.0 months (range, 4.0–49.6 months), the median overall survival (OS) was not reached (95% confidence interval [CI], 25.3 months to not reached) and the 2‐year OS rate was 66.1% (95% CI, 52.1%–76.8%). The median PFS was 11.8 months (95% CI, 8.2–21.0 months), and the 2‐year PFS rate was 35.9% (95% CI, 23.1%–48.9%). Subgroup analysis according to tumor histology or patient age revealed no differences in median PFS or OS. Long‐term follow‐up of toxicities did not identify new safety signals, and no treatment‐related deaths occurred during the study period.Conclusion.Concurrent chemoradiation with nab‐P/C was safe and provided a long‐term survival benefit for patients with locally advanced NSCLC.
AbstractLessons Learned.Recruitment of patients with advanced hepatocellular carcinoma and Child‐Pugh B for sorafenib treatment and additional pharmacokinetic studies is challenging.Patients with Child‐Pugh B liver cirrhosis have high rates of cirrhosis‐related adverse events.Background.Few data are available on the pharmacokinetics (PK) of sorafenib in patients with advanced hepatocellular carcinoma (HCC) and Child‐Pugh B liver cirrhosis. This study aimed to explore the sorafenib PK and its relationship with efficacy and toxicity in these patients.Methods.Patients with advanced HCC and Child‐Pugh B7‐8 liver function were prospectively recruited at a tertiary center. Adverse events (AEs), progression‐free survival (PFS), and overall survival (OS) were recorded. Patients received a starting dose of 200 b.i.d. with toxicity‐adjusted dose escalation to a target dose of 400 mg b.i.d. with PK sampling at fixed time points.Results.Between May 2014 and March 2017, 12 patients were screened, of whom 7 progressed to a terminal stage during the screening (n = 6) or shortly after recruitment (n = 1). The five included patients had median PFS of 3.8 months (range, 1.7–10.8) and OS of 7.4 months (range, 1.7–25.8). Three patients had severe AEs and one patient had a partial response with an OS of 25.8 months. In 2017, the trial was aborted for lack of accrual.Conclusion.Because of low accrual, no conclusion can be drawn on the sorafenib PK in patients with advanced HCC and Child‐Pugh B liver cirrhosis. The poor survival and frequent cirrhosis‐related AEs suggest limited benefit for most of these patients.
AbstractOn May 24, 2019, the Food and Drug Administration approved ruxolitinib for steroid‐refractory acute graft‐versus‐host disease (SR‐aGVHD) in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424‐271 (REACH‐1; NCT02953678), an open‐label, single‐arm, multicenter trial that included 49 patients with grades 2–4 SR‐aGVHD occurring after allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered at 5 mg twice daily, with dose increases to 10 mg twice daily permitted after 3 days in the absence of toxicity. The Day‐28 overall response rate was 57.1% (95% confidence interval [CI]: 42.2–71.2). The median duration of response was 0.5 months (95% CI: 0.3–2.7), and the median time from Day‐28 response to either death or need for new therapy for acute GVHD was 5.7 months (95% CI: 2.2 to not estimable). Common adverse reactions included anemia, thrombocytopenia, neutropenia, infections, edema, bleeding, and elevated transaminases. Ruxolitinib is the first drug approved for treatment of SR‐aGVHD.Implications for Practice.Ruxolitinib is the first Food and Drug Administration–approved treatment for steroid‐refractory acute graft‐versus‐host disease in adult and pediatric patients 12 years and older. Its approval provides a treatment option for the 60% of those patients who do not respond to steroid therapy.
AbstractBackground.The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy are noninferior to 6 months. Our study objectives were to characterize medical oncologists’ perspectives toward the results of the IDEA collaboration and to evaluate how IDEA impacted prescribing patterns of adjuvant FOLFOX and CAPOX in colon cancer.Materials and Methods.A list of questions developed by four medical oncologists regarding IDEA results were formulated and distributed online to gastrointestinal medical oncologists globally. Descriptive statistics and chi‐square tests were used to summarize information.Results.Of 174 responses, 145 were complete and analyzed. Responses were obtained globally from South America (53%); the U.S. and Canada (28%); Europe, Australia, and New Zealand (12%); and Asia (7%). Most clinicians (98%) were aware of the IDEA study. Prior to IDEA, clinicians preferred FOLFOX over CAPOX (81% vs. 19%). Subsequent to IDEA, 55% of clinicians preferred CAPOX over FOLFOX (odds ratio, 5.0; 95% confidence interval, 3.0–8.5; p < .01 compared with pre‐IDEA). Two thirds (68%) of responders tailored duration of adjuvant therapy based on risk stratification. Most oncologists (76%) were more willing to discontinue oxaliplatin early if toxicities develop after the results of IDEA. Half of responders (50%) found that IDEA increased their confidence in decision making for adjuvant treatment; 36% were unchanged, and 15% indicated decreased confidence. Less than half (48%) were comfortable communicating the study results and the concept of a noninferiority trial with patients.Conclusion.IDEA appears to have shifted clinician preference from FOLFOX to CAPOX for adjuvant therapy, and most clinicians now use a risk‐stratified approach in determining duration of adjuvant therapy. Patient education resources may facilitate better communication of IDEA results to patients.Implications for Practice.This global survey illustrates that most gastrointestinal medical oncologists now use a risk‐stratified approach for determining the duration of adjuvant chemotherapy for stage III colon cancer. Clinicians are five times more likely to choose CAPOX over FOLFOX after the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration results.
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