bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune-checkpoint inhibitors among privately insured cancer patients: Utilization pattern and out-of-pocket cost.
Authors: Zhao Hui , Xu Ying , Giordano Sharon H. , Shih Ya-Chen T.
Published: May 2020

e19252

Background: Immune-checkpoint inhibitors (ICI) is a form of immunotherapy that “releases the brakes” on the immune cells to restore antitumor immunity and promote tumor cell death to treat cancer. In March 2011, the United States Food and Drug Administration (FDA) approved ipilimumab, the 1st ICI, to treat advanced-stage melanoma. Since December 2014, FDA successively approved another six ICIs: nivolumab, pembrolizumab, avelumab, durvalumab, cemiplimab, and atezolizumab. Beside melanoma, the treatment indications for these agents have been expanded to renal cell carcinoma, microsatellite instability (MSI)-high malignancies, small-cell lung cancer, non-small-cell lung cancer, and cutaneous squamous cell carcinoma. No study had examined the patterns and out-of-pocket (OOP) costs of ICI among cancer patients (pts) with private insurance. Methods: We used the IBM MarketScan Commercial Claims and Encounters database to document the uptake of ICI from 2011 to 2017. Using the Healthcare Common Procedure Coding System (HCPCS) codes, and national Drug code, we identified ICI claims among pts 18 to 64 years old. OOP cost for ICI was computed as sum of coinsurance, copayment, and deductible. To determine whether financial burden was higher for pts with high-deductible (HD) plans, we dichotomized pts’ insurance plan as HD vs. non-HD. Summary statistics was used to describe the patterns of ICI use. We used Wilcoxon Rank Sum test to compare the OOP by HD status. Results: The study cohort included 7,855 pts with 62,636 ICI claims of ipilimumab, nivolumab, pembrolizumab, avelumab, durvalumab, and atezolizumab between 2011 and 2017. The median age was 57 years and about 56.9% pts were male. Approximately 90% of pts used ICI as monotherapy, and the median number of claims per patient was 4. The most commonly used ICI was nivolumab (55.4%), accounting for about 90% of claims after 2014, followed by lpilimumab (24.6%), pembrolizumab (18.5%). Among the ICI pts, 17.2% enrolled in HD plans and 82.8% had non-HD plans. The median OOP for both HD and non-HD groups was $0, whereas the 3rd quartile of OOP was significantly higher for pts in HD plans ($556 vs. $26, P < 0.01). In addition, approximately 18.7% of pts (17.3% of pts in non-HD and 25.6% in HD plans) paid over $500 OOP per patient for ICI. Conclusions: The use of ICI was dramatically increased as more ICI agents were approved since 2015. Although more than 50% of pts had $0 OOP, possibly due to the out-of-pocket max provision in private insurance, pts with HD plans are especially susceptible to high financial burden of ICIs.
Real-world data of a cohort of patients with soft tissue sarcoma in a single institution of Colombia.
Authors: Pino Luis Eduardo , Triana Ivan Camilo , Ospina Serrano Aylen Vanessa , Segovia Javier , Hennessey Diana Carolina
Published: May 2020

e19259

Background: Soft Tissue Sarcomas (STS) are a group of neoplasm with huge histological diversity and biological behaviors. They have a low prevalence and lack of data, especially in Colombia where there is no specific report of this disease. The objective of this study is to describe clinical characteristics and outcomes of patients with soft tissue sarcoma at Fundación Santafe, a university hospital located in Bogotá. Methods: This is an observational study of a cohort of soft tissue sarcoma patients treated at a single institution with a follow-up of 4 years (2015 - 2019). Clinical, molecular and epidemiological variables were registered, and overall survival was calculated for stage IV sarcomas. For the survival analysis a Kaplan Meier model was used. Results: Twenty-four patients were included. The histologies reported were: Pleomorphic sarcoma 25.0%, Ewing's sarcoma 20.8%, liposarcoma 16.7%, chondrosarcoma 8.3%, leiomiosarcoma 8.3%, synovial sarcoma 8.3%, soft part alveolar sarcoma 8.3%, and dermatofibrosarcoma protuberans 4.3%. OSm for the whole stage IV group was: 30.22m, according to subtypes OSm was: Ewing's sarcoma 37.13 OSm, liposarcoma 11 OSm, chondrosarcoma 12.3 OSm. Only 3 of the cases (2 Ewing's sarcoma and 1 alveolar sarcoma) had multigenic platform information. In these cases, main mutations in BCL2, SOX9, SATB2 and TFE3 were described. In two of the cases PDL1 expression was done with a negative result ( < 1%) (pleomorphic sarcoma and Ewing's sarcoma). Ifosfamide and anthracyclines was the most frequent chemotherapy regimen used, but in two of the cases checkpoint inhibitors were initiated. Conclusions: This real-world cohort of STS have a similar clinical and epidemiological distribution to historic cohorts, but our OSm for Ewing's sarcoma stage IV is longer than reported, even with a case of complete remission after consolidation with autologous bone marrow transplant. Other histologies had a worse prognosis with a less than 12 m OSm. Genomic data were scarce and useless for directed therapies or immunotherapy as usual in STS. [Table: see text]
Landscape of targetable alterations discovered by next generation sequencing demonstrates the role a community hospital can play in precision-guided oncology: Experience from Lenox Hill Hospital.
Authors: Vojnic Morana , Steinberg Jordan , Odintsov Igor , Ziemba Yonah , Hill Lindsay K , Vele Oana , Brunckhorst Keith R. , Hasanovic Adnan
Published: May 2020

e19279

Background: Next generation sequencing (NGS) has become standard of care in aiding diagnosis and treatment of advanced solid cancers, and in conducting clinical trials at large centers. It is imperative that this is expanded to other hospitals that care for the majority of cancer patients. We analyzed NGS reports from our hospital to assess the number of patients who can benefit from approved or investigational targeted therapies. Methods: We analyzed NGS data for 511 solid tumor samples sequenced between January 1, 2018 and December 31, 2019. NGS was performed by GenPath Dx (77%), Caris Life Sciences (16%) or Foundation Medicine (7%). Results: The majority of samples represented advanced stage malignancies and 21% were stage I or II. They originated from the following primaries: 195 lung (37%), 150 gastrointestinal (29%), 64 primary brain (12%), 20 gynecological (4%), 14 skin (3%), 13 head and neck (3%) and 11 sarcomas (1%). 72 samples had mutations in EGFR (14%), 170 in TP53 (33%), 124 in KRAS (24%), 28 in BRAF (6%), and 3 in RET (0.6%). 34/107 (32%) early stage samples harbored an actionable mutation (20 EGFR mutations, 1 MET exon 14 skipping, 4 KRAS G12C, 7 BRAF V600E, 1 FGFR3 amplification and 1 CD74/NRG1 fusion). In contrast, only 58/317 (18%) advanced stage samples had a targetable mutation (p-value = 0.02, χ² test). 76% of EGFR-mutated samples were lung adenocarcinomas, and 19% were primary brain tumors; 54% of these are targetable by FDA-approved EGFR inhibitors. KRAS mutations were found in gastrointestinal (54%), lung (37%) and pancreatic (5%) malignancies. 17 patients had a KRAS G12C mutation and, therefore, could benefit from one of the KRAS G12C inhibitors in early clinical trials. Four samples harbored crizotinib-sensitive mutations (2 MET amplifications and 2 MET exon 14 skipping mutations). Regarding gene fusions, one glioblastoma sample had a PTPRZ-MET fusion and one lung adenocarcinoma sample harbored a CD74-NRG1 fusion. Conclusions: We identified 92/511 samples (18%) with clinically actionable mutations; distributed in 32% early stage and 18% advanced stage disease, indicating that actionable mutations are present at an increased frequency in early stage solid malignancies in our data set and trials to investigate targeted therapy in such settings should be considered. Furthermore, we show that a community-based hospital can be a site for future clinical trials of small molecule inhibitors and bring precision-guided medicine to additional patients.
Molecular profiles and treatment recommendations for invasive lobular carcinoma in a real-world prospective breast cancer registry.
Authors: Lesnikoski Beth-Ann , Crozier Jennifer A. , Srkalovic Gordan , Robinson Patricia A. , Osipo Clodia , Banda Kalyan , Kling Heather M. , Yoder Erin , Audeh William ,   FLEX Investigators Group
Published: May 2020

e19291

Background: Invasive lobular carcinoma (ILC), the second most common histological breast cancer type, comprises 10-15% of breast tumors. Although ILC is thought to have a low risk of relapse, patient survival data vary. ILC treatment guidelines mirror those for invasive ductal carcinoma (IDC); however, these were extrapolated from trials that included predominantly IDC. The FLEX Registry captures data from real-world breast cancer patients; the current sub-study evaluated molecular profiles and treatment recommendations in ILC. Methods: The FLEX Registry (NCT03053193) includes stage I-III primary invasive breast cancer patients who receive 70-gene signature (70-GS)/80-gene signature (80-GS) testing and consent to full transcriptome and clinical data collection. This sub-analysis includes 335 ILC patients and 2,179 IDC patients enrolled from 2017 to present. 70-GS stratified tumors by risk of distant metastasis [High (HR), Low (LR), Ultralow (UL) Risk], and 80-GS classified tumors by molecular subtype (Luminal, HER2, or Basal type). Genomic and clinical data were compared for ILC and IDC using chi-square or Fisher’s exact test. Results: ILC represented 13% of FLEX cases (n = 335/2752); 81% were lymph node-negative, 99% ER-positive, and 94% HER2-negative. Clinical risk assessment (MINDACT criteria) classified 61% of ILC and 53% of IDC as low risk (p = 0.03). 70-GS risk distribution in ILC (18% UL, 51% LR, 31% HR) differed from IDC (13% UL, 34% LR, 53% HR; p < 0.01). Discordance between 70-GS and clinical risk was greater in ILC (43%) than IDC (30%, p < 0.01). 80-GS results also differed between ILC (98% Luminal, 1.6% HER2, 0.3% Basal) and IDC (85% Luminal, 3% HER2, 11% Basal; p < 0.01). Inclusion of chemotherapy (CT) in treatment plans was associated with 70-GS risk (p < 0.01); treatment plans that disagreed with 70-GS results were associated with discordant clinical risk (p < 0.05). Treatment plans disagreed with 70-GS in 15% of ILC and 12% of IDC total cases (p = 0.08), and more frequently in HR cases (25% in ILC, 14% in IDC; p < 0.01). Conclusions: The FLEX Registry includes patients with ILC consistent with real-world breast cancer frequencies. ILC demonstrated genomic risk and subtype profiles distinct from IDC. Treatment plans largely agreed with 70-GS results; however, discordance was more frequent in HR ILC than IDC. Future studies will evaluate clinical outcomes; however, these results demonstrate the added value of molecular profiling in ILC and the utility of real-world registry data in evaluating uncommon breast tumor types. Clinical trial information: NCT03053193 .
Examination of PD-1/PD-L1 inhibitor use and adverse events in a real-world setting.
Authors: Irwin Debra E. , Brady Brenna L.
Published: May 2020

e19294

Background: Immune checkpoint blockade through PD-1 and PD-L1 inhibition is an effective treatment for multiple cancers. This study used administrative claims to examine potential adverse events (AEs) associated with real-world PD-1 or PD-L1 inhibitor use. Methods: Adult patients newly initiating a PD-1 (pembrolizumab or nivolumab) or PD-L1 (atezolizumab, avelumab, or durvalumab) inhibitor from September 1, 2016 to August 30, 2018 were selected in the MarketScan Commercial and Medicare Supplemental Database. Patients were grouped by use of PD-1 or PD-L1 inhibitor; the study period consisted of 90 days baseline and 60 days follow-up around drug initiation. Patients who used both PD-1 and PD-L1 inhibitors during follow-up were excluded. Clinical characteristics were examined during baseline, while AEs were investigated over follow-up. Results: A total of 6,430 patients qualified for the analysis. The majority of the sample (N = 5,956; 93%) received PD-1 inhibitors. Compared to the PD-1 cohort, the PD-L1 cohort was older (64±10 vs. 61±12 yrs) and more likely to be male (61% vs. 56%), p < 0.05. PD-L1 patients were significantly more likely to have history of chronic pulmonary disease (28% vs. 23%) or myocardial infarction (4% vs. 3%) but less likely to have liver disease (2% vs. 0.6%) compared to PD-1 patients, p < 0.05. Lung cancer was the most common diagnosis in both groups (PD-1: 47%; PD-L1: 62%, p < 0.001). The PD-L1 cohort was more likely to have evidence of bladder cancer (36% vs. 5%), while the PD-1 cohort was more likely to have a melanoma (19% vs. 0.8%) or renal cell carcinoma diagnosis (10% vs. 7%), p < 0.05. Over half of the PD-1 (65%) and PD-L1 (61%) patients had metastatic cancer diagnosis during the study period. Incident AEs occurring in > 5% of the sample included dyspnea (PD-1: 13%; PD-L1: 14%), nausea/vomiting (PD-1: 11%; PD-L1: 8%, p < 0.05), anemia (PD-1: 11%; PD-L1: 12%), fatigue (PD-1: 10%; PD-L1: 12%), abdominal pain (PD-1: 7%; PD-L1: 7%), cough (PD-1: 7%; PD-L1: 10%, p < 0.05), back pain (PD-1: 7%; PD-L1: 10%, p < 0.05), constipation (PD-1: 6%; PD-L1: 8%), arthralgia (PD-1: 6%; PD-L1: 6%), pyrexia (PD-1: 5%; PD-L1: 8%, p < 0.01), and edema (PD-1: 6%; PD-L1: 5%). Conclusions: This study assessed real-world AEs associated with PD-1/PD-L1 inhibitor use in the 60 days following first treatment. Results showed AEs are common soon after starting therapy. Although, PD-1 and PD-L1 inhibitors target the same pathway, slightly different AE profiles exist for the two classes. More longitudinal analyses of real-world AEs are needed to better understand potential impacts of prolonged therapy.
Access to molecular testing and targeted molecular therapy among Mexican patients with lung adenocarcinoma.
Authors: González-Gutiérrez Adriana , Salazar-Mejía Carlos Eduardo , Dorsey-Trevino Edgar , Gonzalez Vela Jose Luis , González-Guerrero Juan Francisco , Hernández-Barajas David , Vidal-Gutiérrez Oscar , Oyervides Victor
Published: May 2020

e19296

Background: Precision medicine has led to important changes in the treatment paradigm for patients with lung adenocarcinoma (LA) with mutations in EGFR or rearrangements of ALK or ROS1. The objective of this study is to describe the proportion of patients with LA who had access to molecular testing and targeted molecular therapy at an oncology referral center in Northeast Mexico. Methods: A retrospective study was performed with information gathered from electronic health records of the Hospital Universitario “Dr. José E. González” in Monterrey, Mexico from 2014 to 2019. Patients with LA were identified based on ICD-10 codes (C34) and diagnosis was confirmed with histopathological reports. Results: A total of 316 cases of lung cancer were identified, of which, 194 (64%) were LA, and of those, 117 (60%) had access to molecular testing. Mutations in EGFR were detected in 47%; 38% in men and 59% in women. Rearrangements in ALK were observed in 6.4%, whereas no alterations in ROS1 were seen. Access to molecular testing increased from 2014 to 2019, with a rate of 42% to 67%, respectively. Among patients that were candidates to receive targeted molecular therapy only 37% had access in 2014 versus 66% in 2019. Conclusions: The frequency of mutations in EGFR among our patients with LA showed a high discrepancy with previous studies conducted in countries with a predominantly white population. In Latin America, reports range from 14% to 34% in Argentina and Mexico, respectively. In our study, we identified a higher proportion of mutations in EGFR when compared to what previously reported; however, limited access to molecular testing may bias our results. Despite the advances in treatment for patients with LA, the availability of molecular testing and personalized treatment remains a challenge for developing countries.
Analysis of bleeding risk with concurrent treatment of VEGFR tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors.
Authors: George Tiffany L. , Patel Sandip H. , Wang Tzu-Fei , Mori-Vogt Sherry , Folefac Edmund , Yin Ming
Published: May 2020

e19305

Background: Tyrosine kinase inhibitors (TKIs) of vascular endothelial growth factor receptor (VEGFR) may interfere with the coagulation system making patients susceptible to both hemorrhage and thromboembolism. Some cancer patients require dual treatment with VEGFR TKIs and factor Xa inhibitors. However, the safety of such combination treatment (e.g. bleeding risk) has not been well characterized in the literature. Methods: This retrospective study identified metastatic cancer patients who received VEGFR TKIs (pazopanib, sunitinib, sorafenib, axitinib, regorafenib, vandetanib, lenvatinib, cabozantinib, tivozanib) and Xa inhibitors (low-molecular weight heparin [LMWH] or direct oral anticoagulants [DOACs]- rivaroxaban or apixaban) from 2001 to 2018 at the Ohio State University. We assessed bleeding risks of dual therapy vs factor Xa inhibitors alone, using the same patients as self-controls. We defined bleeding based on criteria from the International Society on Thrombosis and Haemostasis. Fisher’s exact test was used to compare distribution of bleeding severities and the Cox model was used to analyze bleeding risk. Results: A total of 86 patients were included for analysis, with a median age of 56 (range, 34-88). The patient population was predominantly of male gender (69.7%), Caucasian race (89.3%) and renal cell cancer type (48.9%). As some patients had been on both LMWH and DOAC at different time periods, we found that 81 patients received concurrent TKI and LMWH; 19 patients had concurrent TKI and DOAC. Overall, 25 patients developed 29 clinically significant bleeding events (including 8 major bleeding) during concurrent treatment, and 15 patients developed 17 clinically significant bleeding events (4 major bleeding) during factor Xa inhibitor alone over a median follow up of 63 days. We found a statistically higher bleeding risk with concurrent treatment (HR = 2.23, 95% CI, 1.13–4.42, p = 0.02) compared with Xa inhibitor alone. In a stratified analysis, concurrent VEGFR TKI plus LMWH or DOAC both showed a strong trend for elevated bleeding risk. Although there were increased bleeding events with concurrent treatment, there was no significant difference in the proportion of major bleeding (27.6% vs 23.5%, p = 0.76). Median time to first bleeding event was 56 days for concurrent therapy and 72 days for Xa inhibitor alone. Conclusions: Concurrent treatment of VEGFR TKI and factor Xa inhibitors is associated with significantly increased bleeding risk when compared with factor Xa inhibitors alone in metastatic cancer patients.
Real-world evidence: A retrospective-cohort study of castration-resistant advanced prostate cancer (CRAPC) patients treated with abiraterone 1000 mg or 250 mg.
Authors: Smolje Leonel , Niewiadomski Dario , Acuna Claudia Lorena , Gonzalez Cesar , Gonzalez Liliana D , Ares Sandra L. , Muino Marcelo , Garcia Gerardi Carlos , Gil Deza Ernesto , Morgenfeld Eduardo L. , Rivarola Edgardo G. J. , Gercovich Felipe G.
Published: May 2020

e19315

Background: The efficacy of Abiraterone 250 mg with food was established ten years ago (Ryan JCO 2010). Recent publications (Szmulewitz JCO 2018) have concluded that 1000 mg on an empty stomach or 250 mg with food have similar results. This paper focuses on our experience with patients treated with either scheme at Instituto Oncológico Henry Moore (IOHM). Methods: Between July 2013 and December 2019, CRAPC patients were treated with Abiraterone 1000 mg on an empty stomach (Group A) or 250 mg with breakfast (Group B), according to the decision of the attending physician. Both groups received 5 mg of Prednisone twice a day. All cases from Group B were included and they were matched in a 1:2 ratio with Group A by two criteria: age at diagnosis and interval between diagnosis and Abiraterone. We studied: A) response rate of PSA at 12 weeks, B) time to progression, C) post-Abiraterone survival and D) overall survival. Results: We included 99 patients in the study: 66 in Group A and 33 in Group B. The table below shows population characteristics and results. Conclusions: 1) Abiraterone 1000 mg on an empty stomach or 250 mg with food both have similar outcomes. 2) In Argentina, the monthly cost of Abiraterone 1000 mg per patient is equivalent to USD 5,300. This cost can be reduced by 75% with Abiraterone 250 mg with food without losing efficacy. [Table: see text]
Machine learning imputation of Eastern Cooperative Oncology Group performance status (ECOG PS) scores from data in CancerLinQ discovery.
Authors: Agrawal Smita , Narayanan Babu , Chandrashekaraiah Prajwal , M Sai Vinod , Nandi Sourav , Vaidya Vivek , Sun Ping , Cabrera Claudia , Svensson David , Khosla Sajan , Stepanski Edward , Komatsoulis George Anthony
Published: May 2020

e19318

Background: ECOG PS is a prognostic indicator of outcomes, and scores of 0-1 (good ECOG PS) are often required for clinical trial enrollment. Patients treated in non-trial settings often lack ECOG PS scores limiting the ability of Real World Data from these patients to be used in external control arms (ECAs) or to provide optimal specificity for clinical effectiveness research. Machine Learning can be used to impute ECOG PS scores from other clinical data at various points during treatment. Methods: We developed a series of models using logistic regression (LR) or XGBoost (XGB) that impute ECOG PS at initial diagnosis, metastatic diagnosis and final evaluation using a curated Non-Small Cell Lung Cancer cohort of 31,425 patients with at least one ECOG PS score. Results: AUC-ROC values of up to 0.81 could be obtained for imputing a patient’s final ECOG PS, with lower AUC values when imputing ECOG PS at initial and metastatic diagnosis using large numbers (i.e. thousands) of features. We developed more interpretable models with 110 or 40 features with reduced but still satisfactory AUC, with accuracy of predicting good ECOG PS scores of around 80%. Key features were obtained from lab tests, physical exams, comorbidities, medications, age and metastatic status. The table below shows the results of several of these models. Where the models misclassify ECOG PS, the error was rarely greater than 1 grade. Conclusions: ECOG PS is subjective, suggesting that ML based cohort assignment will be sufficiently accurate to support their use in research. Further work will be required to assess if the ML predicted cohorts have different outcomes. [Table: see text]
Prospective review of SPEP orders confirms need for testing algorithm.
Authors: Mazzoni Sandra Ann , Neppalli Amarendra Kumar , Khalil Shadi , Jonahtan Bakos , Kalmuk James , El Nahas Georges , Bray Alexander , Litwin Christine , Greenberg Charles
Published: May 2020

e19326

Background: Serum protein electrophoresis (SPEP) identifies monoclonal proteins associated with plasma cell disorders including multiple myeloma. There are no large prospective studies looking at clinical ordering patterns of SPEPs. This study will determine the percent of monoclonal proteins detected by SPEP testing and factors that are or are not associated with identifying monoclonal proteins. We predict that SPEP testing is commonly ordered and not thoroughly evaluated prompting a need for an algorithm to ensure appropriate use and follow up testing. Methods: In our academic center, we captured data on all SPEP tests ordered from March 17 to June 16, 2019. We chart reviewed each associated patient to collect the following: patient age and sex, SPEP result, hemoglobin, serum albumin, total serum protein, serum calcium, serum creatinine, presence of proteinuria, serum free light chains, immunoglobulins (IgG, IgA, IgM), serum immunofixation, urine protein electrophoresis, urine immunofixation, bone marrow biopsy report, imaging results (bone survey, PET, MRI) and echocardiograms. We ascertained the reason for ordering the SPEP, inpatient or outpatient status of the patient and the ordering department. Results: There were 929 SPEPs ordered. 410 (44%) ordered on “new” patients with no previously identified M-spike. Of the 410 “new” SPEP orders, 57 (14%) detected a M-spike. 8 (2%) led to a diagnosis requiring treatment: 7 new cases of myeloma and 1 case of AL amyloidosis. 108 (26%) of the 410 “new” SPEP orders were ordered in the inpatient setting with 20 “new” M-spikes identified. Only 4 of the 108 inpatient SPEP orders identified a diagnosis requiring treatment—4 cases of myeloma. These patients had SPEPs ordered due to pathologic fractures related to lytic lesions and acute renal failure with other associated CRAB features. Neurologic findings were the most common reason for ordering “new” SPEPs, 106 (26%) of the 410 with only 7 with M-spike—all low risk MGUS. Only 2 of 26 patients were found to have low risk MGUS when SPEP was ordered as part of a rheumatologic work up. All 6 patients with SPEP ordered for dermatologic reasons were negative for M-spike. 23 (40%) of the 57 “new” M-spikes had no follow up testing to determine the clinical significance. Conclusions: This prospective review on the use of SPEP orders in an academic medical center documents the need to provide an algorithm to aide effective use of testing to decrease inpatient ordering and provide guidance on appropriate follow up testing. We found a very low yield with SPEP testing for neurologic, rheumatologic and dermatologic reasons.
Treatment workload by stage and subtype in patients with breast cancer: A SEER-Medicare analysis.
Authors: Cheng Alex , Warner Jeremy Lyle , Levy Mia Alyce
Published: May 2020

e19328

Background: Patients with breast cancer experience significant disruption to their daily lives when undergoing treatment. When treatment workload exceeds the capacity to manage that treatment, patients are less likely to adhere to care plans and likelier to have worse outcomes. The purpose of this study was to assess treatment workload in patients with operable breast cancer in the SEER-Medicare dataset. Methods: Operable (stage I-III) breast cancer patients diagnosed from 2010-2016, > 65 years old at diagnosis, and with 18 months of continuous Medicare part A, B, and D coverage after diagnosis were included in the cohort. We calculated the number of outpatient appointment days, total cumulative inpatient lengths of stay, and distance traveled for patients in the cohort in the 18 months following diagnosis. We compared treatment workload outcomes between patients with stage I and stage III disease and between patients with HER2+ and HER2-/ER+ disease. Results: 35,071 patients met the inclusion criteria. Compared to stage I patients, stage III patients had more median outpatient appointment days (71 vs 50), more median inpatient days (2 vs 0), and greater median distance traveled (1846 vs 1332 miles). Compared to patients with HER2-/ER+ disease, patients with HER2+ disease had more median outpatient appointment days (70 vs 51), and greater median distance traveled (1775 vs 1350 miles). All comparisons were with Mann Whitney U and were statistically significant with P < .001. Conclusions: Patients with operable breast cancer experience a high amount of treatment workload in the first 18 months after diagnosis. These workload measures derived from SEER-Medicare claims differentiate significantly by stage and subtype, with stage III and HER2+ patients experiencing greater treatment workload than stage I and HER2-/ER+ patients respectively. We suspect that greater treatment workload in stage III is attributed to higher intensity of treatment for later stage cancer and associated complications, while greater treatment workload in HER2+ patients is attributed to the use of trastuzumab. [Table: see text]
Long-term proteasome inhibition in US community multiple myeloma (MM) patients (pts) following in-class transition (iCT) from parenteral bortezomib (V) to oral ixazomib (I): Updated real-world (RW) data from US MM-6.
Authors: Girnius Saulius Kazmiems , Yimer Habte Aragaw , Manda Sudhir , Yasenchak Christopher A. , Charu Veena , Lyons Roger M. , Kambhampati Suman , Birhiray Reumu E. , Jhangiani Haresh S. , Boccia Ralph V. , Whidden Presley , Bogard Kim , Cherepanov Dasha , Noga Stephen Joseph , Rifkin Robert M.
Published: May 2020

e19332

Background: US MM-6 is investigating iCT from parenteral V-based induction to all-oral I-lenalidomide-dexamethasone (IRd) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence/duration while maintaining quality of life (QoL) & further improving outcomes in the diverse US community population. Methods: 21 US community sites, including VA hospitals, are enrolling non-transplant-eligible newly diagnosed MM pts with ≥stable disease after 3 cycles of V-based therapy to receive IRd. Pts use mobile & digital devices to collect actigraphy (activity/sleep) data, complete QoL & treatment satisfaction questionnaires, & self-report medication adherence. Primary endpoint: progression-free survival (PFS); key secondary endpoints include: response rates & duration of therapy. Results: As of Nov 18, 2019, 84 pts had been treated (median age 73 [range 49–90] yrs; 44% ≥75 yrs; 49% male; 15% black/African American; 10% Hispanic/Latino; 35% International Staging System stage III disease; 42% lytic bone disease). Comorbidities included hypertension (57%), anemia (44%), fatigue (43%), & peripheral neuropathy (13%). 85% of pts were receiving VRd at the time of iCT. 62% of pts are still on therapy & enrollment is ongoing. After initiating iCT, ≥complete response (CR) rate increased from 4% to 26% (Table). At 8 mos median follow-up, 6 pts had progressed & there were 2 on-study deaths. The 12-mo PFS rate was 86% (95% CI, 73–93) from the start of V-based regimen & from the start of IRd. During IRd treatment, 92% of pts had treatment-emergent adverse events (TEAEs) (48% grade [G] ≥3). G3 TEAEs (≥5% of pts) were diarrhea (7%), pneumonia (6%), syncope (6%), & anemia (5%). TEAEs led to study drug discontinuation in 7% of pts; 36% had serious TEAEs. I/R/d dose was adjusted due to AEs in 39%/39%/29% of pts. Medication adherence (cycles 1–5) was ‘excellent’/‘very good’ in ≥78% of pts reporting adherence. QoL/treatment satisfaction were maintained in pts completing questionnaires. Actigraphy data showed normal activity levels & sleep durations. Conclusions: US MM-6 pts are representative of the RW US MM population & results show that iCT to an oral PI may permit prolonged PI-based therapy with promising efficacy & without impacting pts’ QoL or treatment satisfaction. Clinical trial information: NCT03173092 . [Table: see text]
Overall survival (OS) in metastatic melanoma since the introduction of immunotherapy: A National Cancer Database analysis.
Authors: Singh Sunny R K , Malapati Sindhu Janarthanam , Kumar Rohit , Wang Ding
Published: May 2020

e19333

Background: Metastatic melanoma historically had a very poor prognosis and survival until the utilization of immunotherapy. Ipilimumab, the first immune checkpoint (ICP) inhibitor was approved in March 2011, followed soon after by the approval of PD-1 and PD-L1 inhibitors. We aim to conduct a real-world analysis of survival outcomes before and after 2011 in metastatic melanoma and its subtypes. We will also explore the impact of race on the clinical presentation and outcomes of melanoma. Methods: Adults with metastatic melanoma were identified from the NCDB (2004-2015). Kaplan Meier method was used to estimate survival and Cox proportional hazards model was used to determine hazard ratio (HR) for death after adjusting for age, race, sex, comorbidity index, melanoma type, education, income, insurance, facility type and geographical location. Odds of having metastatic disease at diagnosis were estimated using multivariate log regression analysis. Results: Of the 20,691 metastatic melanoma cases, 19,492 (94.2%) were cutaneous, 326 (1.6%) were ocular and 873 (4.2%) were mucosal. The effect of immunotherapy use on survival in metastatic melanoma was assessed by comparing years 2011-2015 versus 2004-2010. After the introduction of immunotherapy in 2011, the adjusted survival for metastatic melanoma had improved in Caucasians (HR 0.80, p < 0.001, CI 0.77-0.83) but not in African Americans (HR 0.80, p value = 0.08, CI 0.62-1.03). Although, AA constituted a minority in each melanoma group (1.7% cases of cutaneous, 1.5% of ocular and 8.1% of mucosal melanoma), their odds of having metastatic disease at onset was higher in both cutaneous (OR 2.60, p < 0.001 CI 2.28-2.95) and mucosal melanoma (OR 1.85, p < 0.001 CI 1.39-2.47) compared to Caucasians. Conclusions: Real-world data suggested a 20% improvement in survival of metastatic melanoma since the introduction of ICP inhibitors except in the subgroups of ocular melanoma and African Americans. The disproportionately high odds of metastatic disease at presentation in African American patients with melanoma suggests the need for improvement in care delivery, specifically in terms of early detection. [Table: see text]
Outcomes of patients with left ventricular assist device receiving cancer directed therapies.
Authors: Schlam Ilana , Zaghlol Raja , Basyal Binaya , Mohammed Selma , Gallagher Christopher , Barac Ana
Published: May 2020

e19335

Background: Left ventricular assist devices (LVAD) are increasingly utilized in advanced heart failure (HF). There is a paucity of data regarding outcomes of cancer-directed therapies (CDT) in patients with LVAD. The aim of this study was to describe outcomes in this newly identified group of patients. Methods: Institutional LVAD database review to identify patients with cancer diagnosis who had at least 6 months of follow up. Chart review to capture cancer history, CDT and high-severity complications. Results: 12 of the 588 patients who received LVAD were diagnosed with cancer and received CDT. Six patients were males, 9 African Americans and 3 Caucasians. Ischemic cardiomyopathy (CM) was the etiology of HF in 4 (33%) patients, 9 (66%) patients had non-ischemic CM (including: chemotherapy induced n = 3, idiopathic n = 3, myocarditis n = 1, sarcoidosis n = 1). Cancer diagnoses, staging and high severity complications are described in table. The median age of cancer diagnosis was 59 (41-72). The median time from LVAD placement to cancer diagnosis was 21.5 months (3-47). The median number of hospitalizations was 4 (range 1-7). Conclusions: Cancer diagnosis after LVAD placement requires a multidisciplinary approach due to high rates of adverse cardiovascular and cancer related outcomes. To the best of our knowledge this is the first report of patients with LVAD receiving chemo-immunotherapy, they did not tolerate the combination and immunotherapy was discontinued after one cycle, a larger study is required to assess safety in LVAD patients. Larger prospective studies are required to determine outcomes in this complex patient population. [Table: see text]
Real-world treatment patterns among patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19-directed chimeric antigen receptor T-cell therapy (CAR T).
Authors: Jalbert Jessica J. , Arnason Jon E. , Ge Wenzhen , Chen Chieh-I , Ambati Srikanth R. , Wu Ning , Chaudhry Aafia
Published: May 2020

e19351

Background: CAR T, approved in the US as of October 2017, impacted the treatment landscape for patients with relapsed or refractory (R/R) DLBCL after ≥2 lines of therapy, but there is little known about real-world (RW) treatment patterns in patients who fail or do not respond to CAR T. No treatments of proven benefits are available after CAR T treatment failure. The objective of this study was to describe RW treatment patterns after CAR T. Methods: From MarketScan Commercial/Medicare claims databases (2017‒2018) we identified adult DLBCL patients who received approved CD19-directed CAR T (treatment date = index date). Eligible patients had ≥6 months continuous health plan enrollment prior to index date (i.e. baseline period) and were followed until plan disenrollment or December 31, 2018. Patients with a diagnosis of acute lymphoblastic leukemia over the baseline period were excluded. We identified the first and second treatments after CAR T with systemic chemotherapy, targeted therapy, immunotherapy, hematopoietic stem cell transplant (SCT), radiation therapy (RT), or a second round of CAR T therapy. Kaplan–Meier estimators were used to estimate risk of subsequent treatment and time to next treatment. Results: We identified 56 patients with DLBCL treated with CAR T (mean age [SD]: 57.3 years [9.9]; 23.2% female; 80.4% commercially insured). All patients received CAR T in the inpatient setting, median (Q1‒Q3) length of stay was 15 days (12‒19). Out of 56 patients, 19 initiated a treatment following CAR T; risk of subsequent treatment at 6 months post index was 45.6% (95% CI: 25.4‒60.4%) and median days from CAR T to next treatment was 233 days (95% CI: 139‒NA). Out of 19 patients, 3 initiated a second treatment following CAR T, within 8‒69 days of the first treatment. Over a median (Q1‒Q3) follow-up of 139.5 days (90.5‒194) following CAR T, of the 19 patients treated after CAR T, 57.9% were treated with immunotherapy, 36.8% with RT, 26.3% with targeted therapy, 21.1% with SCT, 15.8% with chemotherapy, and 0% with a second round of CAR T. Conclusions: There are few multicenter studies reporting RW treatment patterns in patients who received CAR T. In this study, risk of subsequent treatment at 6 months following CAR T in a RW setting was almost 50%. Although limited by duration of follow-up, our results suggest that additional, effective salvage treatment strategies are needed for patients who do not respond to CAR T or do not achieve a durable response to CAR T. Updated results using 2019 data will be presented.
Incidence and prognosis of patients with pulmonary metastases at diagnosis of primary extrapulmonary malignancy: A population-based study.
Authors: Li Hao , Zhao Xiaoyi , Zhou Zuli , Ning Shaonan
Published: May 2020

e19353

Background: As a sign of advanced malignancy, pulmonary metastases often predict poor prognosis and are notoriously difficult to treat, requiring an interdisciplinary combination of chemotherapy, surgery and radiotherapy. Large-scale and generalizable studies examining the incidence and prognosis of patients with pulmonary metastases are still lacking. Methods: We identified 2,649,261 patients with diagnoses of nonhematologic malignancies originating outside of the pulmonary between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) program. We described the incidence proportion and survival of patients with pulmonary metastases, and determined risk factors and prognostic factors of for pulmonary metastasis. Results: We identified 68,474 patients with pulmonary metastases at diagnosis, accounting for 3.19% of all patients with cancer and 35.94% of those patients with metastatic disease. Tumors with higher lung metastasis rates were pancreas cancer, esophageal cancer, sarcoma, renal cancer, hepatobiliary cancer, all other type of cancer, ovarian cancer and gastric cancer (10.54%, 9.32%, 8.75%, 7.48%, 6.43%, 5.96%, 5.79% and 5.26%, respectively). When considering only patients with distant metastases at diagnosis, The top five types of cancer with pulmonary metastasis were testicular cancer (82.82%), thyroid cancer (72.80%), endometrial cancer (66.87%), renal cancer (66.59%) and cervical cancer (64.89%). Multivariable logistic regression identified several oncology characteristics, such as synchronal bone, brain or liver metastasis (vs without), higher N-stage, and tumor poor pathological differentiation were associated with higher risk of pulmonary metastases. Similar to the risk factors for incidence, more distant metastasis, poor differentiation, higher staging, positive lymph node might also associate with shorter overall survival and cancer-specific survival. Surgery of primary site was a protect factor for survival. Conclusions: For the first time, we provided current generalizable estimates of the incidence and prognosis of patients with pulmonary metastases at diagnosis of an extrapulmonary malignancy. This data may lead to evaluation of early screening of the pulmonary using chest CT scan among patients with newly diagnosed primary extrapulmonary malignancies, and further shape the development of screening and treatment guidelines about pulmonary metastases.
Does targeted therapy dominate in terms of a higher level of effectiveness for a given cost compared to wild-type treatment? An analysis of cost and outcome of metastatic lung cancer patients in Saudi Arabia.
Authors: Da'ar Omar B. , Alkhybri Ali , Alshareed Saud , Alkaiyat Mohammad , Jazieh Abdul Rahman
Published: May 2020

e19361

Background: This study computed and analyzed aggregate and sub-aggregate healthcare costs of lung cancer care by demographic profiles, resource utilization, clinical conditions, and target therapy. Methods: This is a retrospective chart-review and descriptive analysis of resource use and direct medical cost for lung cancer care had at the Oncology Department, King Abdulaziz Medical City for the period 2016-2018. The cost difference between patients receiving targeted therapy (TT) and those with wild-type tumors and the incremental cost-effectiveness ratio (ICER) was performed. The relationship between aggregate cost and demographic profiles, resource utilization, clinical conditions, and treatment therapies using multivariate regression technique was conducted. Results: A total of 35 patients of lung cancer patients with non-small cell lung cancer were analyzed, of which, 34% received targeted therapy; the median age was 62 years (29-84), 43% were ≥ 65 years, 20% were alive; 74% were in stage IV, 69% had visited ED more than twice, and 69% were admitted for non-ICU-related issues. The mean aggregate cost for all patients was USD 197,300 and it was USD 176,000 for TT patients compared with USD 210,600 for non-TT patients. The mean cost for targeted patients was higher for medication components, which accounts for 87.8% of all the costs. On average, the targeted group had USD 34,600 less cost compared with wild type. At least in terms of non-ICU admissions, both groups had on average two admissions. Thus, in terms of ICER, the targeted therapy dominates as it shows lower average aggregate cost for a given level of effectiveness. While longevity (survival) was associated with a higher cost, having stage IV was associated with lower cost for the targeted group compared with wild-type. Generally, being female, > 65 years of age, non-Saudi, and insurance eligibility were associated with lower costs. Conclusions: TT patients had a lower aggregate average cost in spite of expensive medications treatment. This lower aggregate cost presents an added value to the known advantages of patient survival and quality of life.
A cost-utility analysis of apalutamide for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).
Authors: Parmar Ambika , Timilshina Narhari , Emmenegger Urban , Alibhai Shabbir M.H. , Smoragiewicz Martin , Sander Beate , Chan Kelvin K.
Published: May 2020

e19369

Background: The therapeutic landscape for patients with mCSPC has evolved over the last decade given the growing body of evidence demonstrating efficacy for the earlier application of oral androgen receptor signaling inhibitors, such as with abiraterone and enzalutamide. Recently the success of the TITAN trial established the superior efficacy of apalutamide combined with androgen deprivation therapy (ADT), with a 33% reduction in mortality versus ADT alone, and a tolerable toxicity profile. However, with substantially higher costs than ADT alone, the cost-effectiveness of this combination is critical to evaluate. Methods: A cost-utility analysis of apalutamide+ADT versus ADT alone was conducted from the Canadian healthcare perspective. A state-transition model with probabilistic analysis was used to compare the two strategies over a lifetime horizon. Model inputs were informed by the TITAN trial (transition probabilities, adverse events [AE], subsequent therapy), published literature (utilities) and Canadian costing resources (systemic therapy [initial and subsequent], routine care [physician visits, imaging], AE, end-of-life care costs). Primary outcomes included expected life-year gains (LYG), quality-adjusted life-years (QALY), lifetime cost (in 2018 Canadian dollars), and the incremental cost-effectiveness ratio (ICER). Multiple scenario analyses were conducted to assess parameter and model uncertainty. Cost and effectiveness were discounted at 1.5% as per Canadian guidelines. Results: From the base-case analysis expected LYG and QALY for ADT and apalutamide+ADT were 4.11, 5.57 and 3.50, 4.85, respectively. Expected cost over a lifetime horizon was $37,553 and $254,205, respectively. The ICER for apalutamide+ADT as compared to ADT alone was $160,483/QALY. Through scenario analysis, cost-effectiveness of apaluatmide+ADT was achieved with apalutamide price reductions of >50%, relative to a cost-effectiveness threshold (CET) of $100,000/QALY. Scenario analysis of alternative long-term survival expectations with apalutamide+ADT demonstrated cost-effectiveness (relative to CET $100,000/QALY) with expected improvements in the 5-year survival rate of 29% as compared to ADT (versus base-case expected improvement in 5-year survival of 15%). Conclusions: Apalutamide+ADT is unlikely to be cost-effective from the Canadian healthcare perspective at current list prices. Improvement in cost-effectiveness is most likely to be achieved through price reductions in apalutamide drug costs.
Stem cell transplant and financial toxicity: A single-center prospective cohort analysis.
Authors: Hussaini Syed , Ren Yi , Lew Meagan , Bohannon Lauren , Thompson Jillian C , Zafar Yousuf , Sung Anthony Derek
Published: May 2020

e19373

Background: Increasing healthcare costs often result in many individuals and families foregoing required care, delaying care, or non-adhering to prescribed medication. Hematopoietic cell transplantation (HCT) is a highly specialized procedure that has the potential to adversely affect the socioeconomic well-being of patients and their family. Financial well-being in patients undergoing evaluation for HCT has been inadequately studied. In this prospective cohort study, we examined financial toxicity in a cohort of patients being considered for HCT at the Duke Adult Bone Marrow Transplant Clinic. Methods: This is a prospective cohort review of patients age ≥18 years undergoing evaluation for allogeneic HCT between 1/1/2017 – 1/1/2020. Patients that completed a baseline financial health survey and the comprehensive score for financial toxicity-functional assessment of chronic illness therapy (COST-FACIT) survey were included. Financial health was measured via baseline survey and financial distress was assessed via the validated COST-FACIT measure. The primary outcome was financial distress. Results: Of 157 consecutive patients, 112 (71.3%) completed financial toxicity assessments. Of these, 63.4% were male, had a mean age of 61.0, were predominantly white (74.4%), and majority had household incomes less than $90,000 (53.7%). Primary diagnosis at screening was leukemia (35.4%) and myelodysplastic neoplasm (31.7%). Overall, 94.5% noted an inability to see a physician in the prior year due to cost, 76.8% had not filled a prescription due to cost, 73.2% reduced spending on basics like food or clothing to pay for cancer care, 69.5% borrowed money or used a credit card to pay for cancer care, 54.9% used all or a portion of their savings to pay for cancer care, and 54.9% reduced spending on leisure activities like vacations, eating out, or movies to pay for cancer care. Overall, 31 (37.8%) respondents noted mild financial distress while 26 (34.1%) noted moderate-to-high financial distress. Conclusions: Previous studies in the solid tumor and hematological malignancy fields have noted similar results in financial toxicity. However, this is the first study of its kind to demonstrate prevalent financial toxicity present in a cohort of patients undergoing evaluation for HCT. Early interventions by physician and social work led teams may benefit patients who are at risk for financial distress. Future directions include investigating factors associated with high financial toxicity in HCT, and whether financial distress is related to worse outcomes after transplant.