Opioid Prescribing Trends in Women Following Mastectomy or Breast‐Conserving Surgery Before and After the 2014 Federal Reclassification of Hydrocodone

1 month 2 weeks ago
AbstractBackground.Given concerns about suboptimal pain management for actively treated cancer patients following the 2014 federal reclassification of hydrocodone, we examined changes in patterns of opioid prescribing among surgical breast cancer patients.Materials and Methods.Data from a large nationally representative commercial health insurance program from 2009 to 2017 were used to identify women aged 18 years and older who were diagnosed with carcinoma in‐situ or malignant breast cancer and received breast‐conserving surgery or mastectomy from 2010 to 2016. Generalized linear mixed models were used to estimate the adjusted odds ratio (aOR) for receipt of ≥1‐day, >30‐day, or ≥ 90‐day supply of opioids in the 12 months following surgery adjusting for demographics, cancer treatment–related characteristics, and preoperative opioid use.Results.A total of 60,080 patients were included in the study. Surgically treated breast cancer patients in 2015 (aOR = 0.90, 0.84–0.97) and 2016 (aOR = 0.80, 0.74–0.86) were less likely to receive ≥1‐day supply of opioid prescriptions when compared with patients in 2013. Patients who had surgery in 2015 (aOR = 0.89, 0.81–0.98) and 2016 (aOR = 0.80, 0.73–0.87) were also less likely to receive >30‐day supply of prescription opioids in the 12 months following surgery. However, only surgical breast cancer patients in 2016 were less likely to receive ≥90‐day supply (aOR = 0.86, 0.76–0.98).Conclusion.Surgically treated breast cancer patients are less likely to receive short‐ and long‐term opioid prescriptions following the implementation of hydrocodone rescheduling. Further studies on the potential impact of federal policy on cancer patient pain management are needed.Implications for Practice.Clinicians and researchers with diverse perspectives should be included as stakeholders during policy development for restricting opioid prescriptions. Stakeholders can identify potential unintended consequences early and help identify methods to mitigate concerns, specifically as it relates to policy that influences how providers manage pain for actively treated cancer patients. This work shows how federal policy may have led to declines in opioid prescribing for breast cancer patients who underwent mastectomy or breast‐conserving surgery.
Derrick C. Gibson, Lin-Na Chou, Mukaila A. Raȷi, Jacques G. Baillargeon, Yong-Fang Kuo

Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy‐Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy

1 month 2 weeks ago
AbstractBackground.NEPA, a combination antiemetic of a neurokinin‐1 (NK1) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5‐HT3RA, palonosetron] offers 5‐day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsifier, or solubility enhancer. A phase III study of patients receiving cisplatin found no infusion‐site or anaphylactic reactions related to IV NEPA. However, hypersensitivity reactions and anaphylaxis have been reported with other IV NK1RAs, particularly fosaprepitant in patients receiving anthracycline‐cyclophosphamide (AC)‐based chemotherapy. This study evaluated the safety and efficacy of IV NEPA in the AC setting.Materials and Methods.This phase IIIb, multinational, randomized, double‐blind study enrolled females with breast cancer naive to highly or moderately emetogenic chemotherapy. Patients were randomized to receive a single 30‐minute infusion of IV NEPA or single oral NEPA capsule on day 1 prior to AC, in repeated (up to 4) cycles. Oral dexamethasone was given to all patients on day 1 only.Results.A total of 402 patients were included. The adverse event (AE) profiles were similar for IV and oral NEPA and consistent with those expected. Most AEs were mild or moderate with a similarly low incidence of treatment‐related AEs in both groups. There were no treatment‐related injection‐site AEs and no reports of hypersensitivity or anaphylaxis. The efficacy of IV and oral NEPA were similar, with high complete response (no emesis/no rescue) rates observed in cycle 1 (overall [0–120 hours] 73.0% IV NEPA, 77.3% oral NEPA) and maintained over subsequent cycles.Conclusion.IV NEPA was highly effective and safe with no associated hypersensitivity and injection‐site reactions in patients receiving AC.Implications for Practice.As a combination of a neurokinin‐1 (NK1) receptor antagonist (RA) and 5‐HT3RA, NEPA offers 5‐day chemotherapy‐induced nausea and vomiting prevention with a single dose and an opportunity to improve adherence to antiemetic guidelines. In this randomized multinational phase IIIb study, intravenous (IV) NEPA (fosnetupitant/palonosetron) was safe and highly effective in patients receiving multiple cycles of anthracycline‐cyclophosphamide (AC)‐based chemotherapy. Unlike other IV NK1RAs, the IV NEPA combination solution does not require any surfactant, emulsifier, or solubility enhancer and contains no allergenic excipients. Hypersensitivity reactions and anaphylaxis have been reported with other IV NK1RAs, most commonly with fosaprepitant in the AC setting. Importantly, there were no injection‐site or hypersensitivity reactions associated with IV NEPA.
Lee Schwartzberg, Rudolph Navari, Rebecca Clark-Snow, Ekaterine Arkania, Irena Radyukova, Kamal Patel, Daniel Voisin, Giada Rizzi, Rita Wickham, Richard J. Gralla, Matti Aapro, Eric Roeland

Olanzapine Versus Haloperidol for Treatment of Delirium in Patients with Advanced Cancer: A Phase III Randomized Clinical Trial

1 month 2 weeks ago
AbstractBackground.Treatment of delirium often includes haloperidol. Second‐generation antipsychotics like olanzapine have emerged as an alternative with possibly fewer side effects. The aim of this multicenter, phase III, randomized clinical trial was to compare the efficacy and tolerability of olanzapine with haloperidol for the treatment of delirium in hospitalized patients with advanced cancer.Materials and Methods.Eligible adult patients (≥18 years) with advanced cancer and delirium (Delirium Rating Scale‐Revised‐98 [DRS‐R‐98] total score ≥17.75) were randomized 1:1 to receive either haloperidol or olanzapine (age‐adjusted, titratable doses). Primary endpoint was delirium response rate (DRR), defined as number of patients with DRS‐R‐98 severity score <15.25 and ≥4.5 points reduction. Secondary endpoints included time to response (TTR), tolerability, and delirium‐related distress.Results.Between January 2011 and June 2016, 98 patients were included in the intention‐to‐treat analysis. DRR was 45% (95% confidence interval [CI], 31–59) for olanzapine and 57% (95% CI, 43–71) for haloperidol (Δ DRR −12%; odds ratio [OR], 0.61; 95% CI, 0.2–1.4; p = .23). Mean TTR was 4.5 days (95% CI, 3.2–5.9 days) for olanzapine and 2.8 days (95% CI, 1.9–3.7 days; p = .18) for haloperidol. Grade ≥3 treatment‐related adverse events occurred in 5 patients (10.2%) and 10 patients (20.4%) in the olanzapine and haloperidol arm, respectively. Distress rates were similar in both groups. The study was terminated early because of futility.Conclusion.Delirium treatment with olanzapine in hospitalized patients with advanced cancer did not result in improvement of DRR or TTR compared with haloperidol. Clinical trial identification number. NCT01539733. Dutch Trial Register. NTR2559.Implications for Practice.Guidelines recommend that pharmacological interventions for delirium treatment in adults with cancer should be limited to patients who have distressing delirium symptoms. It was suggested that atypical antipsychotics, such as olanzapine, outperform haloperidol in efficacy and safety. However, collective data comparing the efficacy and safety of typical versus atypical antipsychotics in patients with cancer are limited. If targeted and judicious use of antipsychotics is considered for the treatment of delirium in patients with advanced cancer, this study demonstrated that there was no statistically significant difference in response to haloperidol or olanzapine. Olanzapine showed an overall better safety profile compared with haloperidol, although this difference was not statistically significant.
Maurice J.D.L. van der Vorst, Elisabeth C.W. Neefjes, Manon S.A. Boddaert, Bea A.T.T. Verdegaal, Aart Beeker, Saskia C.C. Teunissen, Aartjan T.F. Beekman, Janneke A. Wilschut, Johannes Berkhof, Wouter W.A. Zuurmond, Henk M.W. Verheul

Challenges and Opportunities to Updating Prescribing Information for Longstanding Oncology Drugs

1 month 2 weeks ago
AbstractA number of important drugs used to treat cancer—many of which serve as the backbone of modern chemotherapy regimens—have outdated prescribing information in their drug labeling. The Food and Drug Administration is undertaking a pilot project to develop a process and criteria for updating prescribing information for longstanding oncology drugs, based on the breadth of knowledge the cancer community has accumulated with the use of these drugs over time. This article highlights a number of considerations for labeling updates, including selecting priorities for updating; data sources and evidentiary criteria; as well as the risks, challenges, and opportunities for iterative review to ensure prescribing information for oncology drugs remains relevant to current clinical practice.
Erin P. Balogh, Andrew B. Bindman, S. Gail Eckhardt, Susan Halabi, R. Donald Harvey, Ishmael Jaiyesimi, Rebecca Miksad, Harold L. Moses, Sharyl J. Nass, Richard L. Schilsky, Steven Sun, Josephine M. Torrente, Katherine E. Warren

Prognostic Values of Long Noncoding RNA linc00152 in Various Carcinomas: An Updated Systematic Review and Meta‐Analysis

1 month 2 weeks ago
AbstractDysregulation of the long noncoding RNA linc00152 has been reported in various solid tumors. Here, we performed a synthetic analysis to clarify the clinical value of linc00152 as a prognostic indicator in malignant tumors. Article collection was conducted using several electronic databases, including PubMed, Web of Science, Medline, OVID, and Embase (up to February 13, 2018). The meta‐analysis comprised nine original studies and 808 total patients. The application of a random‐effects model revealed significant positive association between high expression level of linc00152 and lymph node metastasis (odds ratio [OR] = 2.93, 95% confidence interval [CI]: 1.88–4.57, p < .0001; I2 = 48.8, p = .119) and negative association with low‐grade cancer (OR = 2.43, 95% CI: 1.51–3.92; I2 = 61.7, p = .033), while with tumor recurrence (hazard ratio [HR] = 3.32, 95% CI: 1.98–5.57, p < .0001; I2 = 0, p = .451) by fixed‐effects model as the low heterogeneity. As demonstrated via the application of the fixed‐effects model, Linc00152 overexpression is positively related to poor overall survival (pooled HR = 1.98, 95% CI: 1.70–2.31, p < .0001; I2 = 0%, p = .756) and poor disease‐free survival (HR = 1.66, 95% CI: 1.20–2.29, p < .0001; I2 = 75.8%, p = .042) in human solid cancers. Statistically significant associations were additionally found with cancer type, sample size, and follow‐up time. In conclusion, linc00152 is of potential value as a novel biomarker of lymph node metastasis and prognosis in human cancer.Implications for Practice.linc00152 is of potential value as a novel biomarker of lymph node metastasis and prognosis in human cancer.
Han Wang, Yang Liu, Aifa Tang

Access to Novel Drugs for Non‐Small Cell Lung Cancer in Central and Southeastern Europe: A Central European Cooperative Oncology Group Analysis

1 month 2 weeks ago
AbstractBackground.Treatment of non‐small cell lung cancer (NSCLC) improved substantially in the last decades. Novel targeted and immune‐oncologic drugs were introduced into routine treatment. Despite accelerated development and subsequent drug registrations by the European Medicinal Agency (EMA), novel drugs for NSCLC are poorly accessible in Central and Eastern European (CEE) countries.Material and Methods.The Central European Cooperative Oncology Group conducted a survey among experts from 10 CEE countries to provide an overview on the availability of novel drugs for NSCLC and time from registration to reimbursement decision in their countries.Results.Although first‐generation epidermal growth factor receptor tyrosine kinase inhibitors were reimbursed and available in all countries, for other registered therapies—even for ALK inhibitors and checkpoint inhibitors in first‐line—there were apparent gaps in availability and/or reimbursement. There was a trend for better availability of drugs with longer time from EMA marketing authorization. Substantial differences in access to novel drugs among CEE countries were observed. In general, the availability of drugs is not in accordance with the Magnitude of Clinical Benefit Scale (MCBS), as defined by the European Society for Medical Oncology (ESMO). Time spans between drug registrations and national decisions on reimbursement vary greatly, from less than 3 months in one country to more than 1 year in the majority of countries.Conclusion.The access to novel drugs for NSCLC in CEE countries is suboptimal. To enable access to the most effective compounds within the shortest possible time, reimbursement decisions should be faster and ESMO MCBS should be incorporated into decision making.
Tanja Cufer, Tudor E. Ciuleanu, Peter Berzinec, Gabriela Galffy, Marko Jakopovic, Jacek Jassem, Dragana Jovanovic, Zhasmina Mihaylova, Gyula Ostoros, Christiane Thallinger, Milada Zemanova, Christoph Zielinski

Blood‐Based Next‐Generation Sequencing Analysis of Appendiceal Cancers

1 month 2 weeks ago
AbstractBackground.Appendiceal cancers (ACs) are rare. The genomic landscape of ACs has not been well studied. The aim of this study was to confirm the feasibility of next‐generation sequencing (NGS) using circulating tumor DNA (ctDNA) in ACs and characterize common genomic alterations.Materials and Methods.Molecular alterations in 372 plasma samples from 303 patients with AC using clinical‐grade NGS of ctDNA (Guardant360) across multiple institutions were evaluated. Test detects single nucleotide variants in 54–73 genes, copy number amplifications, fusions, and indels in selected genes.Results.A total of 303 patients with AC were evaluated, of which 169 (56%) were female. Median age was 56.8 (25–83) years. ctDNA NGS testing was performed on 372 plasma samples; 48 patients had testing performed twice, 9 patients had testing performed three times, and 1 patient had testing performed four times. Genomic alterations were defined in 207 (n = 207/372, 55.6%) samples, and 288 alterations were identified excluding variants of uncertain significance and synonymous mutations. Alterations were identified in at least one sample from 184 patients; TP53‐associated genes (n = 71, 38.6%), KRAS (n = 33, 17.9%), APC (n = 14, 7.6%), EGFR (n = 12, 6.5%), BRAF (n = 11, 5.9%), NF1 (n = 10, 5.4%), MYC (n = 9, 4.9%), GNAS (n = 8, 4.3%), MET (n = 6, 3.3%), PIK3CA (n = 5, 2.7%), and ATM (n = 5, 2.7%). Other low‐frequency but clinically relevant genomic alterations were as follows: AR (n = 4, 2.2%), TERT (n = 4, 2.2%), ERBB2 (n = 4, 2.2%), SMAD4 (n = 3, 1.6%), CDK4 (n = 2, 1.1%), NRAS (n = 2, 1.1%), FGFR1 (n = 2, 1.1%), FGFR2 (n = 2, 1.1%), PTEN (n = 2, 1.1%), RB1 (n = 2, 1.1%), and CDK6, CDKN2A, BRCA1, BRCA2, JAK2, IDH2, MAPK, NTRK1, CDH1, ARID1A, and PDGFRA (n = 1, 0.5%).Conclusion.Evaluation of ctDNA is feasible among patients with AC. The frequency of genomic alterations is similar to that previously reported in tissue NGS. Liquid biopsies are not invasive and can provide personalized options for targeted therapies in patients with AC.Implications for Practice.The complexity of appendiceal cancer and its unique genomic characteristics suggest that customized combination therapy may be required for many patients. Theoretically, as more oncogenic pathways are discovered and more targeted therapies are approved, customized treatment based on the patient's unique molecular profile will lead to personalized care and improve patient outcomes. Liquid biopsies are noninvasive, cost‐effective, and promising methods that provide patients with access to personalized treatment.
Walid L. Shaib, Katerina Zakka, Charles Staley III, Ali Roberts, Mehmet Akce, Christina Wu, Olatun&#x0237;i B. Alese, Bassel F. El-Rayes

The Impact of Nonsteroidal Anti‐Inflammatory Drugs, Beta Blockers, and Metformin on the Efficacy of Anti‐PD‐1 Therapy in Advanced Melanoma

1 month 2 weeks ago
AbstractAnti–programmed cell death protein‐1 (anti‐PD‐1) therapy has greatly improved outcomes of patients with melanoma; however, many fail to respond. Although preclinical studies suggest a potentially synergistic relationship with anti‐PD‐1 therapy and certain concurrent medications, their clinical role remains unclear. Here, we retrospectively evaluated the use of nonsteroidal anti‐inflammatory drugs (NSAIDs) and other drugs in 330 patients with melanoma treated with anti‐PD‐1 therapy from four academic centers. In the cohort, 37% of patients used NSAIDs including aspirin (acetylsalicylic acid; ASA; 47%), cyclooxygenase (COX)‐2 inhibitors (2%), and non‐ASA/nonselective COX inhibitor NSAIDs (59%). The objective response rates (ORRs) were similar in patients with NSAID (43.4%) and no NSAID (41.3%) use with no significant difference in overall suvival (OS). There was a trend toward improved progression‐free survival (PFS) in patients who took NSAIDs (median PFS: 8.5 vs. 5.2 months; p = .054). Most patients (71.3%) took NSAIDs once daily or as needed. Multivariate analysis did not reveal an association with NSAID use with ORR, PFS, or OS. Concurrent use of metformin or beta blockers did not affect ORR, PFS, or OS. Our study found no conclusive association of concurrent NSAID or other medication use with improved outcomes in patients with melanoma treated with anti‐PD‐1 therapy. Larger and more systematic analysis is required to confirm these findings.
Daniel Y. Wang, Jennifer L. McQuade, Rajat R. Rai, John J. Park, Shilin Zhao, Fei Ye, Kathryn E. Beckermann, Samuel M. Rubinstein, Romany Johnpulle, Georgina V. Long, Matteo S. Carlino, Alexander M. Menzies, Michael A. Davies, Douglas B. Johnson

Extended Survival After Surgical Resection for Pituitary Metastases: Clinical Features, Management, and Outcomes of Metastatic Disease to the Sella

1 month 2 weeks ago
AbstractBackground.Patients with pituitary metastasis (PM) have a relatively poor prognosis. We describe the presentation, management, and outcomes of patients with PM.Subjects, Materials, and Methods.We performed a retrospective review of patients diagnosed with PM at a single institution from 1996 to 2015. Eighty‐five patients diagnosed with metastasis to the pituitary or sella turcica by pathology or based on a combination of neuroimaging and clinical findings were included. Univariate and multivariable Cox regressions evaluated associations between clinical factors and overall survival.Results.The most frequent sites of primary malignancies resulting in PM were lung (26%) and breast (26%). Median age at diagnosis was 60 years (range, 18–95). The most common complaints at diagnosis included visual deficits (62%), headache (47%), and cranial nerve palsy (31%). Seventy percent of patients had pituitary insufficiency—adrenal insufficiency (59%), hypothyroidism (59%), or diabetes insipidus (28%). Management of PM included radiation therapy (76%), chemotherapy (68%), surgical resection (21%), or combination therapy (71%). Fifty percent and 52% of patients who received surgical treatment and irradiation, respectively, reported symptomatic improvement. Median overall survival (OS) was 16.5 months (95% confidence interval: 10.7–25.4). On multivariable analysis, a primary cancer site other than lung or breast (p = .020), age <60 years (p = .030), and surgical resection (p = .016) were associated with longer OS.Conclusion.Patients <60 years of age, those with primary tumor sites other than lung or breast, and those who undergo surgical resection of the pituitary lesion may have prolonged survival. Surgical resection and radiation treatment resulted in symptomatic improvement in ~50% of patients.Implications for Practice.This study is the largest original series of patients with metastatic disease to the sella. In patients with pituitary metastasis, younger age, primary site other than lung or breast, and metastatic resection may prolong survival. Resection and radiation led to symptomatic improvement in ∼50% of patients. Seventy percent of patients had hypopituitarism. These hormonal deficiencies can be life threatening and can result in substantial morbidity if left untreated. Patients should be treated using a multimodality approach—including a potential role for surgery, radiation, chemotherapy, and hormone replacement—with the goal of improving survival and quality of life.
Krupa R. Patel, Junting Zheng, Viviane Tabar, Marc A. Cohen, Monica Girotra

Intratumoral Immunotherapy—Update 2019

1 month 2 weeks ago
AbstractIntratumoral immunotherapies aim to trigger local and systemic immunologic responses via direct injection of immunostimulatory agents with the goal of tumor cell lysis, followed by release of tumor‐derived antigens and subsequent activation of tumor‐specific effector T cells. In 2019, a multitude of intratumoral immunotherapies with varied mechanisms of action, including nononcolytic viral therapies such as PV‐10 and toll‐like receptor 9 agonists and oncolytic viral therapies such as CAVATAK, Pexa‐Vec, and HF10, have been extensively evaluated in clinical trials and demonstrated promising antitumor activity with tolerable toxicities in melanoma and other solid tumor types. Talimogene laherparepvec (T‐VEC), a genetically modified herpes simplex virus type 1–based oncolytic immunotherapy, is the first oncolytic virus approved by the U.S. Food and Drug Administration for the treatment of unresectable melanoma recurrent after initial surgery. In patients with unresectable metastatic melanoma, T‐VEC demonstrated a superior durable response rate (continuous complete response or partial response lasting ≥6 months) over subcutaneous GM‐CSF (16.3% vs. 2.1%; p < .001). Responses were seen in both injected and uninjected lesions including visceral lesions, suggesting a systemic antitumor response. When combined with immune checkpoint inhibitors, T‐VEC significantly improved response rates compared with single agent; similar results were seen with combinations of checkpoint inhibitors and other intratumoral therapies such as CAVATAK, HF10, and TLR9 agonists. In this review, we highlight recent results from clinical trials of key intratumoral immunotherapies that are being evaluated in the clinic, with a focus on T‐VEC in the treatment of advanced melanoma as a model for future solid tumor indications.Implications for Practice.This review provides oncologists with the latest information on the development of key intratumoral immunotherapies, particularly oncolytic viruses. Currently, T‐VEC is the only U.S. Food and Drug Administration (FDA)‐approved oncolytic immunotherapy. This article highlights the efficacy and safety data from clinical trials of T‐VEC both as monotherapy and in combination with immune checkpoint inhibitors. This review summarizes current knowledge on intratumoral therapies, a novel modality with increased utility in cancer treatment, and T‐VEC, the only U.S. FDA‐approved oncolytic viral therapy, for medical oncologists. This review evaluates approaches to incorporate T‐VEC into daily practice to offer the possibility of response in selected melanoma patients with manageable adverse events as compared with other available immunotherapies.
Omid Hamid, Rubina Ismail, Igor Puzanov

Development and Validation of a Prognostic Nomogram to Guide Decision‐Making for High‐Grade Digestive Neuroendocrine Neoplasms

1 month 2 weeks ago
AbstractBackground.The objective of this study was to develop and validate a nomogram to predict 1‐year overall survival (OS) and 2‐year OS in patients with high‐grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy.Subjects, Materials, and Methods.We performed a retrospective analysis of 223 patients with NENs of the gut and hepato‐biliary‐pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one.Results.The final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C‐index was 0.761 for OS, and the bias‐corrected C‐index was 0.744. Predictions correlated well with observed 1‐year and 2‐year outcomes (judged by eye). The area under the time‐dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log‐rank p < .001).Conclusion.The validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials.Implications for Practice.The high‐grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum‐based chemotherapy may not bring clinical benefit for the low‐risk patients.
Zhenyu Lin, Haihong Wang, Yixuan Zhang, Guiling Li, Guoliang Pi, Xianjun Yu, Yaobing Chen, Kaizhou Jin, Liangkai Chen, Shengli Yang, Ying Zhu, Gang Wu, Jie Chen, Tao Zhang

Polypharmacy, Inappropriate Medication Use, and Drug Interactions in Older Korean Patients with Cancer Receiving First‐Line Palliative Chemotherapy

1 month 3 weeks ago
AbstractBackground.Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug–drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes.Subjects, Materials, and Methods.This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first‐line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first‐line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi‐comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment‐related toxicity, and hospitalization using logistic regression and Cox regression analyses.Results.In total, 301 patients (median age 75 years; range, 70–93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0–14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18–2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment‐related toxicity.Conclusion.Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period.Implications for Practice.This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug–drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer.
Soo&#x0237;ung Hong, Ju Hyun Lee, Eun Kyeong Chun, Kwang-Il Kim, Jin Won Kim, Se Hyun Kim, Yun-Gyoo Lee, In Gyu Hwang, Jin Young Kim, Su-Jin Koh, Yoon Ho Ko, Seong Hoon Shin, In Sook Woo, Tae-Yong Kim, Ji Yeon Baek, Hyun Jung Kim, Hyo Jung Kim, Myung Ah…

Initial Results from Mobile Low‐Dose Computerized Tomographic Lung Cancer Screening Unit: Improved Outcomes for Underserved Populations

1 month 3 weeks ago
AbstractIntroduction.The National Lung Screening Trial (NLST) demonstrated that screening high‐risk patients with low‐dose computed tomography (CT) of the chest reduces lung cancer mortality compared with screening with chest x‐ray. Uninsured and Medicaid patients usually lack access to this hospital‐based screening test because of geographic and socioeconomic factors. We hypothesized that a mobile screening unit would improve access and confer the benefits demonstrated by the NLST to this underserved group, which is most at risk of lung cancer deaths.Patients and Methods.We created a mobile unit by building a Samsung BodyTom portable 32‐slice low‐dose CT scanner into a 35‐foot coach; it delivers high‐quality images for both soft tissue and bone and includes a waiting area and high‐speed wireless internet connection for fast image transfer. The unit was extensively tested to show robustness and stability of mobile equipment. This project was designed to screen uninsured and underinsured patients, otherwise with eligibility criteria identical to that of the National Lung Screening Trial, with the only difference being exclusion of patients eligible for Medicare (which provides financial coverage for CT‐based lung cancer screening).Results.We screened 550 patients (20% black, 3% Hispanic, 70% rural) with a male‐to‐female ratio of 1.1:1, median age 61 years (range, 55–64), and found 12 lung cancers at initial screen (2.2%), including 6 at stage I–II (58% of total lung cancers early stage) and 38 Lung‐RADS 4 (highly suspicious) lesions that are being followed closely. Incidental findings included nonlung cancers and coronary artery disease.Discussion.In this initial pilot study, using the first mobile low‐dose whole body CT screening unit in the U.S., the initial cancer detection rate is comparable to that reported in the NLST, despite excluding patients over the age of 64 years who have Medicare coverage, but with marked improvement of screening rates specifically in underserved sociodemographic, racial, and ethnic groups and with better outcomes than conventionally found in the underserved and at lower cost per case.Implications for Practice.This study shows clearly that a mobile low‐dose CT scanning unit allows effective lung cancer screening for underserved populations, such as impoverished African Americans, Hispanics, Native Americans, or isolated rural groups, and has a pick‐up rate of 1% for early stage disease. If confirmed in a planned randomized trial, this will be policy changing, as these groups usually present with advanced disease; this approach will produce better survival data at lower cost per case.
Derek Raghavan, Mellisa Wheeler, Darcy Doege, John D. Doty II, Henri Levy, Kia A. Dungan, Lauren M. Davis, James M. Robinson, Edward S. Kim, Kathryn F. Mileham, James Oliver, Daniel Carrizosa

Clinical Outcomes of Second‐Line Chemotherapy in Patients with Previously Treated Advanced Thymic Carcinoma: A Retrospective Analysis of 191 Patients from the NEJ023 Study

1 month 3 weeks ago
AbstractBackground.Owing to the rarity of this tumor, there is limited information about second‐line chemotherapy for patients with previously treated advanced thymic carcinoma.Material and Methods.We performed a multi‐institutional, retrospective study named NEJ023 for patients with advanced thymic carcinoma. Patients without indications for curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions in the North East Japan Study Group. Demographic and clinicopathologic characteristics, data on treatment methods, and outcomes of second‐line chemotherapy were obtained from medical records.Results.In total, 191 patients were enrolled in this study. Second‐line chemotherapy included platinum‐based doublets in 57.6% of patients, other multidrug chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide) in 13.6%, and monotherapy in 28.8%. The median follow‐up time was 50.5 months, and the median overall survival (OS) from the start of second‐line chemotherapy was 22.4 (95% confidence interval, 17.5‐26.7) months. The average response rate (RR) was 20.0% overall; it was 21.6% for patients treated with platinum‐based doublet chemotherapy, 13.6% for those treated with other multidrug chemotherapy, and 19.6% for those treated with single agent chemotherapy. There was no significant difference in OS between platinum‐based doublet chemotherapy, other multidrug chemotherapy, and monotherapy (the median OS was 22.4, 25.7, and 21.4 months, respectively).Conclusion.The median OS was 22.4 months in patients with advanced thymic carcinoma treated with second‐line chemotherapy. There were no significant differences in RR and OS between monotherapy and multidrug chemotherapy in this study.Implications for Practice.Owing to the rarity of this tumor, there is limited information about second‐line chemotherapy for patients with previously treated advanced thymic carcinoma. This is the largest data for those patients treated with second‐line chemotherapy. This study suggests there is no significant difference in efficacy between monotherapy and multidrug chemotherapy for previously treated advanced thymic carcinoma. This result can support the adequacy to select monotherapy as treatment of those patients.
Kazunari Tateishi, Ryo Ko, Takehito Shukuya, Yusuke Okuma, Satoshi Watanabe, Shoichi Kuyama, Kyoko Murase, Yoko Tsukita, Hironori Ashinuma, Taku Nakagawa, Kazutsugu Uematsu, Mika Nakao, Yoshiaki Mori, Kyoichi Kaira, Atsuto Mouri, Takao Miyabayashi,…

An Analysis of Recent FDA Oncology Scientific Publications

1 month 3 weeks ago
AbstractIn addition to its primary regulatory role, the Office of Hematology and Oncology Products at the U.S. Food and Drug Administration (FDA) is engaged in many forms of scientific authorship. During the period of 2010 to 2018, FDA oncology staff contributed to 356 publications in the scientific literature. Here, we collaborated with analysts in the Office of Program Planning, Analysis, and Evaluation at the National Institute of General Medical Sciences, National Institutes of Health (NIH), to present a series of analyses aimed at quantifying the characteristics and potential impact of these contributions, as well as characterizing the areas of work addressed. We found that FDA oncology papers are enriched for high‐impact publications and have about two times the number of citations as an average NIH‐funded paper. Further impact of the publications was measured based on the presence of 65 publications that were cited by guidelines and 12 publications cited by publicly listed clinical trials. The results seen here are promising in determining the impact of FDA oncology publication work but prompt further investigation into longer‐term impacts, such as the influence of this work on other regulatory activities at FDA.Implications for Practice.This article describes the first comprehensive study of scientific publications produced by U.S. Food and Drug Administration (FDA) oncology staff. The analysis illustrates that staff are highly engaged in publishing in the scientific literature in addition to completing regulatory review work. Publications are generally in clinical medicine, consistent with the large number of medical oncologists working at the Office of Hematology and Oncology Products (OHOP). OHOP publications generally focus either on communicating important regulatory work (approval summaries) or highlighting regulatory science issues to encourage dialogue with the scientific community (commentaries, reviews, and expert working papers). The analysis also suggests that several FDA oncology publications may influence clinical guidelines, but further work is needed to evaluate impact.
Julie A. Schneider, Andrew C. Miklos, James Onken, Yutao Gong, Anna Maria Calcagno, Gideon M. Blumenthal, Richard Aragon, Richard Pazdur

Physical Activity and Exercise in Lung Cancer Care: Will Promises Be Fulfilled?

1 month 3 weeks ago
AbstractLung cancer remains the leading cause of cancer‐related death worldwide. Affected patients frequently experience debilitating disease‐related symptoms, including dyspnea, cough, fatigue, anxiety, depression, insomnia, and pain, despite the progresses achieved in term of treatment efficacy.Physical activity and exercise are nonpharmacological interventions that have been shown to improve fatigue, quality of life, cardiorespiratory fitness, pulmonary function, muscle mass and strength, and psychological status in patients with lung cancer. Moreover, physical fitness levels, especially cardiorespiratory endurance and muscular strength, are demonstrated to be independent predictors of survival. Nevertheless, patients with lung cancer frequently present insufficient levels of physical activity and exercise, and these may contribute to quality of life impairment, reduction in functional capacity with skeletal muscle atrophy or weakness, and worsening of symptoms, particularly dyspnea.The molecular bases underlying the potential impact of exercise on the fitness and treatment outcome of patients with lung cancer are still elusive. Counteracting specific cancer cells’ acquired capabilities (hallmarks of cancer), together with preventing treatment‐induced adverse events, represent main candidate mechanisms.To date, the potential impact of physical activity and exercise in lung cancer remains to be fully appreciated, and no specific exercise guidelines for patients with lung cancer are available. In this article, we perform an in‐depth review of the evidence supporting physical activity and exercise in lung cancer and suggest that integrating this kind of intervention within the framework of a global, multidimensional approach, taking into account also nutritional and psychological aspects, might be the most effective strategy.Implications for Practice.Although growing evidence supports the safety and efficacy of exercise in lung cancer, both after surgery and during and after medical treatments, most patients are insufficiently active or sedentary. Engaging in exercise programs is particularly arduous for patients with lung cancer, mainly because of a series of physical and psychosocial disease‐related barriers (including the smoking stigma). A continuous collaboration among oncologists and cancer exercise specialists is urgently needed in order to develop tailored programs based on patients’ needs, preferences, and physical and psychological status. In this regard, benefit of exercise appears to be potentially enhanced when administered as a multidimensional, comprehensive approach to patients’ well‐being.
Alice Avancini, Giulia Sartori, Anastasios Gkountakos, Miriam Casali, Ilaria Trestini, Daniela Tregnago, Emilio Bria, Lee W. Jones, Michele Milella, Massimo Lanza, Sara Pilotto

Effect of a Skills Training for Oncologists and a Patient Communication Aid on Shared Decision Making About Palliative Systemic Treatment: A Randomized Clinical Trial

1 month 3 weeks ago
AbstractBackground.Palliative systematic treatment offers uncertain and often limited benefits, and the burden can be high. Hence, treatment decisions require shared decision making (SDM). This trial examined the independent and combined effect of an oncologist training and a patient communication aid on SDM.Methods.In this multicenter randomized controlled trial with four parallel arms (2016–2018), oncologists (n = 31) were randomized to receive SDM communication skills training or not. The training consisted of a reader, two group sessions, a booster session, and a consultation room tool (10 hours). Patients (n = 194) with advanced cancer were randomized to receive a patient communication aid or not. The aid consisted of education on SDM, a question prompt list, and a value clarification exercise. The primary outcome was observed SDM as rated by blinded observers from audio‐recorded consultations. Secondary outcomes included patient‐reported SDM, patient and oncologist satisfaction, patients’ decisional conflict, patient quality of life 3 months after consultation, consultation duration, and the decision made.Results.The oncologist training had a large positive effect on observed SDM (Cohen's d = 1.12) and on patient‐reported SDM (d = 0.73). The patient communication aid did not improve SDM. The combination of interventions did not add to the effect of training oncologists only. The interventions affected neither patient nor oncologist satisfaction with the consultation nor patients’ decisional conflict, quality of life, consultation duration, or the decision made.Conclusion.Training medical oncologists in SDM about palliative systemic treatment improves both observed and patient‐reported SDM. A patient communication aid does not. The incorporation of skills training in (continuing) educational programs for medical oncologists is likely to stimulate the widely advocated uptake of shared decision making in clinical practice. Trial registration. Netherlands Trial Registry NTR 5489.Implications for Practice.Treatment for advanced cancer offers uncertain and often small benefits, and the burden can be high. Hence, treatment decisions require shared decision making (SDM). SDM is increasingly advocated for ethical reasons and for its beneficial effect on patient outcomes. Few initiatives to stimulate SDM are evaluated in robust designs. This randomized controlled trial shows that training medical oncologists improves both observed and patient‐reported SDM in clinical encounters (n = 194). A preconsultation communication aid for patients did not add to the effect of training oncologists. SDM training effectively changes oncologists’ practice and should be implemented in (continuing) educational programs.
Inge Henselmans, Hanneke W.M. van Laarhoven, Pomme van Maarschalkerweerd, Hanneke C.J.M. de Haes, Marcel G.W. Di&#x0237;kgraaf, Dirk&#x0237;e W. Sommei&#x0237;er, Petronella B. Ottevanger, Helle-Brit Fiebrich, Serge Dohmen, Geert-Jan Creemers, Filip Y.F…

Prognostic and Predictive Value of Microsatellite Instability, Inflammatory Reaction and PD‐L1 in Gastric Cancer Patients Treated with Either Adjuvant 5‐FU/LV or Sequential FOLFIRI Followed by Cisplatin and Docetaxel: A Translational Analysis from the…

1 month 3 weeks ago
AbstractBackground.Patients with high microsatellite instability (MSI) gastric cancer (GC) show improved survival and no benefit or harm from adjuvant and/or perioperative chemotherapy. The role of immune microenvironment in GC is largely unknown.Materials and Methods.In the present study, 256 tumor tissue blocks were centrally collected from patients enrolled in ITACA‐S, a randomized adjuvant trial of 5‐FU/LV versus sequential FOLFIRI and cisplatin‐docetaxel. MSI status was assessed by multiplex PCR, inflammatory reaction by H p = .02; HR, 0.40; p = .02) and high inflammatory reaction (HR, 0.55; p = .010; HR, 0.53; p = .008) but not for PD‐L1. At multivariable analysis, only MSI showed an independent association with both DFS (p = .02) and OS (p = .01), whereas inflammatory reaction showed an independent association only with OS (p = .04). Patients with tumor PD‐L1 ≥ 1% had a significantly longer DFS in sequential chemotherapy than in than 5‐FU/LV arm (interaction p = .04) and a trend for OS (interaction p = .12).Conclusion.Our data suggest that MSI status could be a useful prognostic biomarker in patients with radically resected stage II–III GC and should be used as stratification factor in future trials. Tumor PD‐L1 ≥ 1% should be further investigated as a potential predictor of benefit from intensive chemotherapy.Implications for Practice.In this post hoc analysis of patients with radically resected gastric cancer randomized to an intensive sequential chemotherapy regimen versus 5‐FU/LV monotherapy as adjuvant treatment in the ITACA‐S trial, MSI‐high status was independently associated with better disease‐free survival and overall survival (OS) and inflammatory reaction was independently associated with better OS. Moreover, tumor PD‐L1 expression ≥1% was associated with greater benefit from intensive sequential chemotherapy compared with 5‐fluorouracil plus leucovorin (5‐FU/LV), whereas PD‐L1 expression <1% was not, conditioning a statistically significant interaction between such biomarker and treatment arms. The meta‐analysis of individual patients’ data from available studies could yield data on the role of MSI status that could inform clinical decisions.
Maria Di Bartolomeo, Federica Morano, Alessandra Raimondi, Rosalba Miceli, Salvatore Corallo, Elena Tamborini, Federica Perrone, Maria Antista, Monica Niger, Alessandro Pellegrinelli, Giovanni Randon, Filippo Pagani, Antonia Martinetti, Giovanni Fuca,…

Mortality of Pregnancy Following Breast Cancer Diagnoses in Taiwanese Women

1 month 3 weeks ago
AbstractBackground.This work examined the association between pregnancy after breast cancer (BC) diagnosis and total mortality in Taiwanese patients with BC.Materials and Methods.The Taiwan Cancer Registry, National Health Insurance database, and Taiwan National Death Certificate database were reviewed. Patients who became pregnant after being diagnosed with BC were selected (n = 249). Four nonpregnant patients with BC were selected and matched to every pregnant patient with BC by age at diagnosis, year at diagnosis, and propensity score based on disease stage, tumor size, node involvement, and histological grade. The disease‐free time interval for the selected control needed to have been longer than the time interval between the cancer diagnosis and pregnancy for the index case. Follow‐up was calculated from the pregnancy date of the index case to the date of death or December 31, 2014, whichever came first. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).Results.After adjusting for age, year at BC diagnosis, stage, positive nodes, and hormone therapy, patients with BC who became pregnant after their cancer diagnosis had lower total mortality than did the comparison group (HR = 0.44, 95% CI = 0.23–0.84), including that of estrogen receptor‐positive patients (HR = 0.23, 95% CI = 0.07–0.77). The inverse association was more pronounced for those who became pregnant more than 3 years after diagnosis (HR = 0.19, 95% CI = 0.05–0.78).Conclusion.Our nationwide retrospective analysis revealed that pregnancy after BC diagnosis was associated with lower mortality than that of nonpregnant patients with BC at a similar age, year at diagnosis, and clinical characteristics.Implications for Practice.This article provides high‐level evidence based on an Asian population for pregnancy counseling after a breast cancer diagnosis, including for patients with estrogen receptor‐positive cancers. The study also revealed the optimal time for patients who would like to become pregnant after breast cancer.
Shu-Chun Chuang, Ching-Hung Lin, Yen-Shen Lu, Chao Agnes Hsiung
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