bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of azole antifungals with survival in patients with non-small cell lung cancer receiving immunotherapy.
Authors: Sebastian Nikhil , Stokes William A. , Behera Madhusmita , Jiang Renjian , Gutman David , Giuste Felipe , Burns Abigail , Ramalingam Selvi , Sukhatme Vidula , Lowe Michael C. , Ramalingam Suresh S. , Sukhatme Vikas , Moghanaki Drew
Published: June 2021

e18777

Background: Preclinical data suggest certain azole derivatives may have antitumor efficacy and modulate responses to immune checkpoint inhibitors (ICIs). Clinical evidence of synergy can support ongoing research that is investigating the role of repurposing current FDA-approved azole medications to improve outcomes in people with non-small cell lung cancer (NSCLC). We evaluated the association of concomitant azole drugs in a population of NSCLC patients treated with ICI within the Veterans Health Administration. Methods: We conducted a retrospective cohort study of veterans diagnosed with NSCLC between 2010-2018 who were treated with ICI. Receipt of azole drugs was defined as taking a systemic azole within 90 days of ICI therapy. Overall survival (OS) was measured from the start of ICI therapy using Cox-Proportional Hazard (PH) multivariable regression. Patients whose earliest azole administration occurred more than 30 days after initiation of ICI were excluded. Results: We identified 3,413 Veterans treated with ICI; of these, 324 (9.5%) were treated with an azole, most commonly clotrimazole (3.0%) and fluconazole (2.5%). Patients had predominantly stage IV disease (40.8%) at initial diagnosis, followed by stage III (27.1%), stage I-II (19.9%), and unknown stage (12.1%). There was no significant difference in OS multivariable analysis (HR = 0.93 [0.81-1.06]; p = 0.28). Propensity score-matched analysis with 324 patients in each cohort also did not measure a significant difference in OS (HR = 0.89 [0.75-1.06]; p = 0.18) between patients who received any azole versus those who did not. When evaluating specific azole agents on multivariable analysis, there was an association of higher OS with receipt of clotrimazole (HR = 0.72 [0.56 – 0.92]; p = 0.009) and more than one azole (HR = 0.71 [0.53-0.96]; p = 0.026) when compared with no azole. There was an association of shorter OS with miconazole (HR = 1.92 [1.30-2.832]; p = 0.001) and no association with itraconazole (p = 0.08), fluconazole (p = 0.20), or ketoconazole (p = 0.87). In the matched analysis of 102 clotrimazole patients versus no azole, OS was longer in patients who received clotrimazole (HR = 0.76; 95% CI 0.55 – 1.04; p = 0.087), although this effect was not statistically significant. Conclusions: This analysis demonstrated a trend towards longer survival with concomitant clotrimazole and ICI for advanced NSCLC. This association was not seen for other azole mediations.
Real-world BRAF testing patterns for patients with metastatic colorectal cancer (mCRC), metastatic melanoma, and non-small cell lung cancer (NSCLC).
Authors: Edwards Michelle L. , Levin Rebecca , Abraham Anup , Amari Diana T. , Kelton John M. , Vieira Maria Cecilia
Published: June 2021

e18778

Background: BRAF mutations are estimated to occur in up to 10% of people with colorectal cancer, 45% with melanoma, and 2-4% with NSCLC and generally represent a poor prognosis for these patients. The National Comprehensive Cancer Network (NCCN) recommends BRAF testing for patients with mCRC, melanoma and NSCLC, however adherence to guidelines and real-world testing rates are not well known. This study describes real-world BRAF testing rates among mCRC, m-melanoma and NSCLC patients. Methods: We performed a retrospective study of adult patients diagnosed with mCRC or m-melanoma from 1/2013 to 11/2020 in the nationwide Flatiron Health EHR-derived de-identified database and with NSCLC from 1/2013 to 11/2020 in the ConcertAI Definitive Oncology Dataset. We measured the proportion of patients receiving a BRAF test and timing of testing in relation to diagnosis and treatment line, concentrating the latter on a limited time frame when there was a stable period of testing (2018-2019 for mCRC and m-melanoma; 2018 for NSCLC). Results: We included 21,758 patients with mCRC, 4,276 patients with m-melanoma, and 12,236 patients with NSCLC of whom 52.7%, 92.0% and 17.2%, respectively, received a BRAF test. Testing rates for mCRC and NSCLC increased over time (mCRC: 27.3% in 2013, 49.9% in 2016, 71.4% in 2020; NSCLC: 6.4% in 2013, 13.5% in 2016 and 29.5% in 2018) and were relatively stable for m-melanoma (94.5% in 2013, 90.6% in 2016, 89.5% in 2020). Among BRAF-tested mCRC patients in 2018-2019 (70.3%, n=5,874), 7.8% were tested before metastatic (m-) diagnosis, with median time from test to m-diagnosis of 8.5 months; 32.1% on or after m-diagnosis and before 1L and 55.8% on or after 1L, with median time from m-diagnosis to test of 1.4 months. Among BRAF-tested m-melanoma patients in 2018-2019 (91.7%, n=1,174), 31.0% were tested before m-diagnosis, with median time from test to m-diagnosis of 9.5 months; 62.2% on or after m-diagnosis and before 1L and 2.5% on or after 1L, with median time from m-diagnosis to test of 0.0 months. Among BRAF-tested NSCLC patients in 2018 (29.5%, n=2,010), 3.0% were tested before earliest diagnosis, with median time from test to diagnosis of 0.3 months; 24.6% on or after earliest diagnosis and before 1L and 15.4% on or after 1L, with median time from diagnosis to test of 1.1 months. (For about 60% of the BRAF-tested patients, it was not possible to identify at which stage of treatment the test was conducted). Conclusions: BRAF testing rates were highest among m-melanoma patients, followed by mCRC and NSCLC. Testing rates for mCRC and NSCLC increased from 2013 to 2020, which may have been in response to guideline changes and availability of targeted treatments. The majority of BRAF testing occurred before 1L in melanoma and NSCLC, and on or after 1L in mCRC.
Clinical trials participation is directly influenced by the information received by cancer patients (pts) and caregivers: Real-world evidence with the use of a specialized digital health platform.
Authors: Greenfeld-Barsky Keren , Hasid Lior , Vorobiof Daniel A. , Malki Eliran
Published: June 2021

e18779

Background: Clinical trials (CT) participation is both crucial for medical advancement and an important treatment option, at times the only one, for oncological pts. However, only an estimate of ̃3% of cancer pts worldwide enrolls into such trials. Different factors have been implicated in underlying this low participation rate, with little current data on patients’ own perspective. In this study, pts & caregivers’ perception, knowledge and experience with CT were assessed via a unique digital health platform. Methods: 290 American and Israeli members of Belong.life cancer application (app) anonymously & voluntarily replied to a 10 questions survey detailing their demographics, diagnosis, and experience with CT as a treatment option. Results: 234 participants were pts (81%) and 56 (19%) caregivers. 73% of participants were US based. 35 participants (12%) were < 50 years of age (yoa), 94 (32%) were 50-59 yoa, 117 (40%) were 60-69 and 44 (15%) were > 70 yoa. There were 79 males and 211 females.The most common diagnosis was breast cancer in 74 (26%), hematologic in 36 (12%), lung in 35 (12%), colorectal in 26 (9%) and ovarian in 26 (9%). Stages were 4 in 117 (40%) and 3 in 52 (18%), early (1&2) in 73 (25%). 134 (46%) have not heard about CT participation as a treatment option. Among 125 participants of the 134 who were not familiar with CT as a treatment option, 115 (92%) stated they would like to learn more about it. Among the 156 participants who were acquainted with this option, 52 (33%) heard about it from medical staff, 41(26%) from multiple online resources, and 39 (25%) only through the Belong.life app. Only 23 participants (8%) previously participated in a CT. The most common reason for not participating was not being offered this treatment option (55, 49%) followed by lack of suitable trials for their condition (26, 23%). The most common reason for considering it was to receive an innovative treatment (60, 44%). Conclusions: Almost half of the pts and caregivers were not aware of CT participation as a valid treatment option. Among them, nearly all have expressed an interest to be better informed. This significant dissonance was also evident among those aware but who were not offered to participate, while expressing a favorable perception regarding participation. While the medical staff is a key source for CT awareness, and whilst patients are exposed to multiple online sources of information, this survey confirmed that 25% of Belong.life members received information about CT availability and participation singly from the app and 8% of them actively participated in a clinical trial. In sum, emphasis should be placed on providing personally tailored CT information to all cancer patients and caregivers. Digital health platforms are an important source for patients CT awareness.
Thrombotic complications with SARS-CoV-2 infection in patients with cancer on high-risk therapies: Data from the COVID-19 and Cancer Consortium (CCC19).
Authors: Gulati Shuchi , Shah Surbhi , Kulkarni Amit , Desai Aakash , Fu Julie , Zon Rebecca , Kumar Vaibhav , Hsu Chih-Yuan , Hwang Clara , Doroshow Deborah Blythe , Akpan Imo , Girard Jennifer , Yu Peter Paul , McKay Rana R. , Bakouny Ziad , Connors Jean , Shah Dimpy P. , Warner Jeremy Lyle , Rosovsky Rachel Pam Greenerger , Grivas Petros
Published: June 2021

e18788

Background: Patients (pts) with cancer have a high risk of venous thromboembolic (VTE) complications, further enhanced by anti-cancer treatments, specifically hormonal therapies, targeted therapies (VEGF inhibitors, other TKIs) and immune checkpoint inhibitors (ICIs). We hypothesized that high-risk therapies would predispose pts with cancer and COVID-19 to higher risk of VTE complications. Methods: CCC19 is the largest international registry (NCT04354701) recording outcomes of pts with cancer and COVID-19. The registry was queried for hospitalized pts who developed VTE and received systemic cancer treatment in the year prior to COVID-19. Incidence of VTE was analyzed as the primary endpoint; 30-day any cause mortality & need for ICU admission at baseline were secondary endpoints in pts with and without VTE respectively. Pts were stratified by treatment type and time from last treatment dose: <2 wk, 2-4 wk, 1-3 months (mos), 3-12 mos. Results: As of February 9th 2021, 4217 hospitalized pts with complications data were present in the registry. 1867 (44%) pts had received systemic anti-cancer therapy within the year prior to COVID-19 and were analyzed. There were a total of 186 (10%) VTE events. Of these, VTE incidence was 141 (10.5%) in pts with solid tumors and 57 (9%) in pts with hematologic malignancies. Overall 30-day mortality was 20% and 22% in pts with and without VTE respectively, while direct admission to ICU at presentation was seen in 17% and 10% of pts with and without VTE, respectively. Treatment timing and drug exposures are below (Table). Receipt of systemic anti-cancer treatment within 3 mos vs 3-12 mos was associated with increased rate of VTE, OR 2.44, 95% CI 1.18-5.84, p=0.011 (univariate Fisher test). Conclusions: We describe the incidence of VTE events in pts with cancer and COVID-19 with recent systemic cancer therapy. ICI and VEGFi were associated with numerically higher rates of VTE; other examined drugs and drug classes were not. Timing of therapy appears to modify risk of VTE. Although retrospective, with possible selection and confounding biases, our analysis suggests that factors other than anti-cancer drug exposures may drive VTE events in this population.[Table: see text]
Early mortality in metastatic cancer: A SEER population data analysis.
Authors: Globus Opher , Sagie Shira , Lavine Noy , Barchana Daniel Itshak , Urban Damien
Published: June 2021

e18789

Background: Overall survival from cancer has continuously improved over the last thirty years. This is due, in part, to advances in systemic treatment of some cancers resulting in clinically significant increases in long-term survival. Despite these improvements in long-term survival, many patients die quickly after a diagnosis of metastatic cancer, possibly being denied the opportunity to benefit from these recent advances in cancer treatment. To identify the scope and predictors of early mortality in de novo metastatic cancer, we analyzed population-based data, focusing on patients with early mortality. Methods: Using the Survival, Epidemiology and End Results (SEER) Database we analyzed adult patients who presented with de-novo metastatic solid malignancies diagnosed between 2008-2016. We defined early mortality as 1- and 2-month mortality. Factors associated with early mortality were analyzed including primary site of cancer and demographics. Correlations between categorical variables were analyzed with chi squared tests and survival data was derived from life tables using STATA I/C 12.1. Results: Of 519,553 patients identified, 273,976 (53%) were males, 411,041 (79%) were white, 213,325 (41%) had lung cancer, 65,679 (13%) colorectal cancer and 49,139 (10%) pancreatic cancer. One - and two - month cancer specific mortality was 12.4% and 22.5% respectively for the entire cohort. Mortality from cancer in the first two months after diagnosis decreased only marginally between 2008 and 2016 (23.4% and 21.6 %, respectively). Cancers with the highest 2-month cancer specific mortality rates were liver (39.5%), pancreatic (36.3%), lung (26.8%), gastroesophageal (23.7%), and urothelial (21.2%). Cancers with the lowest 2-month mortality rate were breast (10.4%) and prostate cancer (5%). Patients who presented with liver metastases had a clinically significant higher 2- month cancer specific mortality rate (29% vs. 18% p < 0.001), brain metastases were associated with a milder increase in 2-month cancer specific mortality (25%vs 21% p < 0.001) and bone metastases were not associated with a clinically significant difference in 2-month cancer specific mortality (22% vs 21%, p = 0.047). Other factors associated with early mortality included increasing age, low income, and living in a rural area. Conclusions: Over 21% of newly diagnosed metastatic cancer patients die within 2 months of their diagnosis, with little improvement over the last decade, rendering this an urgent unmet need in cancer care. Further research is urgently required to better identify the causative and treatable factors of early mortality in cancer patients.
Cancer therapy related dysphonia: Analysis of real-world FAERS data.
Authors: Wang Shuai , Kaur Anahat , Viteri Malone Mariuxi Alexandra , Elrafei Tarek N. , Steinberg Lewis , Kumar Abhishek
Published: June 2021

e18794

Background: Dysphonia is a rare and under-reported adverse event. It is associated with the use of several cancer drugs. Dysphonia has been included as possible side effect on packet insert (PI) for some medications, like regorafenib, lenvatinib and axitinib. However, dysphonia has not been reported on multiple other drugs. We aimed to conduct a more comprehensive study to generate signal for dysphonia as adverse effect of drugs used for oncologic indications. Methods: The United States Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database, a pharmacovigilance database, was used to extract data. All reported cases of dysphonia in the database were filtered for an indication of cancer. Descriptive analysis was conducted using SPSS 26. Results: Total 41840 cases of dysphonia were extracted from FAERS database. Out of these, cancer as an indication for medication use was noted in 2996 cases. Dysphonia was reported as side effect of 30 medications. Some of the most common medications were regorafenib (n=463), cabozantinib (290), lenvatinib (178), axitinib (176) and palbociclib (126) as noted in Table. Dysphonia was not listed as adverse reaction on PI for cabozantinib, palbociclib, sorafenib and oxaliplatin. However, it has been reported for regorafenib, lenvatinib and axitinib. Median age at diagnosis was 66 years (interquartile range 59-73). Dysphonia was reported more commonly in males (51.5%) as compared to females (46.2%). Reactions were reported to the FDA more commonly by consumers (53.3% cases) as compared to healthcare professionals (44.5% cases). Conclusions: This study demonstrates signal of developing dysphonia in patients receiving certain cancer directed medications based on FAERS database. It is worth noting that some of the suspect medications identified in this study do not have dysphonia listed as known adverse effect on accompanying package insert. Further studies need to be conducted to confirm if causal relationship exists between use of these drugs and development of dysphonia. Detailed description of five drugs used for oncologic indications with highest reported cases of dysphonia as adverse effect.[Table: see text]
Incidence and severity of systemic allergic reactions (SAR) reported with chemotherapeutic drugs.
Authors: Thomas Beulah Elsa , Murugan Anju , Varayathu Hrishi , Sangi Lalram , Rani Sonia , Somayaji Shalaka , Mathew Smruthy Ann , Mathew Hephzibah Sara , Gupta Sunny Kumar , Kumar Dr Goutham , Tripathi Priyank , Mufti Suhail Sayeed , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah
Published: June 2021

e18802

Background: SAR, a known adverse event of cancer therapy has variable severity. Despite the availability of many approved grading tools, there is still a lack of a globally applicable grading system. To address this, World Allergy Organization (WAO) created a uniform 5-grade classification system which was modified recently to be applicable for all SAR’s. This study aims to understand the incidence and severity of chemotherapy induced SAR and overall response rate (ORR) of rechallenged drugs in a tertiary cancer center. Methods: A retrospective single centered analysis of 103 patients with chemotherapy induced SAR was carried out. Patients were stratified based on age, gender, drugs given, dose number and severity of reaction. We used Modified WAO Grading System for assessing the severity. Descriptive statistics was applied to decipher the data. ORR is defined as the proportion of patients who have a partial or complete response to rechallenged drugs using RECIST Criteria for solid tumors and Lugano Classification for lymphoma. Results: Among 103 patients who reported SAR, 63.1% were female and 64.1% patients were less than 60 years of age. Among the 22 drugs, median dose number was high for Oxaliplatin (6) and Carboplatin (5). SAR was more observed with Paclitaxel (20.39%), Carboplatin (17.48%) and Rituximab (13.59%). However, carboplatin and rituximab had more incidence of grade 1 SAR(25.92% and 29.63% respectively). Grade 1 SAR (39.80%) were reported the highest followed by grade 3 (29.13%), grade 5 (13.59%), grade 2 (11.65%), and grade 4 (5.83%). Cetuximab precipitated the most grade 5 reactions (33.33%). Among patients exhibiting SAR with Paclitaxel, 42.86% were switched to alternatives, Nab-paclitaxel (28.57%) being preferred the most. Carboplatin was changed to cisplatin in 16.66% patients and Nanosomal docetaxel lipid suspension replaced docetaxel in 42.86% patients who reported SAR with carboplatin and docetaxel respectively. Rituximab was rechallenged the most (11.65%) off which one patient had reaction. ORR was observed to be 62.5% and 50% among rechallenged Paclitaxel and Rituximab respectively. The incidence of SAR is depicted in the below table. Conclusions: The study inferred that most SAR reactions occurred with Paclitaxel and Carboplatin. Oxaliplatin and Carboplatin presented with delayed SAR. Grade 1 and grade 3 reaction were relatively more. Cetuximab reported the most grade 5 reactions. ORR of rechallenged drugs should be monitored in further larger studies.[Table: see text]
Impact and predictors of readmission in hypercalcemia of malignancy: Findings of a nationwide analysis.
Authors: Baral Binav , Salazar Miguel , Prado Victor , Gauto Estefania , Upadhyay Shristi , Shrivastava Trilok , Chhabra Navika , Rosen Fred R.
Published: June 2021

e18809

Background: Hypercalcemia of malignancy (HCM) is common in cancer. It is a sign of advanced malignancy and associated with poor outcomes. Although a well-known phenomenon, treatment options are limited and recurrence leading to readmissions is common, increasing morbidity and mortality. We attempt to explore the mortality, healthcare resource utilization, 30-day readmission rate and independent predictors of readmission for HCM. Methods: We queried the 2017 National Readmission Database (NRD) of adults readmitted within 30 days after index admission for HCM with a concomitant diagnosis of solid tumors. T test was used for continuous variables and chi square test was used for categorical variables. Multivariate regression was used to identify predictors for unplanned readmissions. Results: A total of 14,323 patients with solid tumors were admitted with HCM. The 30-day readmission rate was 24.9%. Common causes for readmission were sepsis, respiratory failure, hypercalcemia, distant metastases and AKI. At 30 days, readmitted patients were less likely to be discharged compared to patients admitted initially due to hypercalcemia (27.4 vs 30.8%; P<0.01). Readmitted patients had a higher in-hospital mortality at 30 days (1.5 vs. 0.1%; P<0.01), more incidence of chemotherapy induced pancytopenia (3.8 vs 2.5%; P<0.01), mechanical ventilation (5.8 vs 4.7%; P=0.05) and venous thromboembolism (8.3 vs 5.9%; P<0.01). Total economic burden of readmission was $251 million in total charges and $62.6 million in total costs. Adjusting for age and comorbidities, independent predictors of readmission were anemia of chronic disease, iron deficiency anemia and obesity. Conversely, predictors for lower odds of readmission were disposition to skilled facility and discharge with home health care services (Table). Conclusions: Nationally, HCM has a high rate of readmissions with increased morbidity and mortality making it a consequential healthcare burden. Among causes of readmission, potentially targetable include AKI and sepsis while among readmission predictors, iron deficiency anemia and anemia of chronic disease warrant further attention. Similarly, negative predictors highlight the importance of proper disposition planning and supportive care in malignancy.[Table: see text]
Patient and caregiver experience with an online, open-access, standardized, evidence-based, cancer drug and supportive care educational platform.
Authors: Gilreath Jeffrey A , Stuart James A. , Wilds Brandon , Lo Mimi , Greenly Anthony , Liu Haopeng , Stenehjem David D.
Published: June 2021

e18811

Background: An open-access, web-based platform was developed to provide standardized, evidence-based information, that is cancer regimen-specific and supportive care focused. Online content was provided in the English language only for more than 200 anti-neoplastic regimens. A survey was conducted to determine reasons adult patients and their caregivers seek internet-based cancer drug information, and to evaluate if there is an unmet need for improved oncology therapy education. Methods: Between February 2020 and January 2021, patients and caregivers completed an online anonymous, English language survey deployed on the website www.chemoexperts.com. Results: A total of 1,021 website users responded. The majority of users were from North America (75%). Female respondents comprised 65% of the population and users self-identified as being a patient (67%), or family member/caregiver (33%). The mean age of respondents was 60.7 years (+ 16.2). Roughly two-thirds (66.4%) had a college degree. The majority of respondents reported they were either currently receiving (59.6%), or planning to receive (27.4%) treatment, however patients of all education levels, and in all phases of treatment (before, during, and after) sought online drug information. Clinical drug information education was reportedly provided by a doctor (68.9%), nurse (40.9%), physician assistant or nurse practitioner (23.8%), or pharmacist (15%), while 23% did not receive any education from clinical staff. Modes of education received by participants included printed material (73.9%), teaching in person (52.3%), and/or other internet sites (27.5%). Reasons for visiting the website were reported as follows: seeking additional information (92%), did not know what questions to ask (12%), looking at treatment alternatives (10%), forgot to ask questions (5%), not enough information given (11%), not enough time to ask questions (5%), and afraid to ask questions (2%). Respondents could mark all reasons. Among content sections, the percentage of users reported the side effect section as being the most useful. However, section usefulness varied based upon age, phase of treatment, and baseline education level. Overall, 86% reported finding the information they were looking for on the website. Conclusions: The majority of respondents received education from a health care provider, but not all. It is possible that the current pandemic prevented some patients from receiving education when in-person teaching was not available. However, many patients and caregivers still use the internet to seek additional drug information. These data highlight a continued unmet need for patients using online sources when searching for cancer drug and supportive care information. Further work is required to determine whether supplemental online, education can improve outcomes while reducing adverse effects.
Does the precision oncology medicine development pathway deliver value for health systems?
Authors: Henderson Raymond , French Declan , Stewart Elaine , Smart Dave , Idica Adam , Clark Jordan , Eckstein Markus , Lawler Mark
Published: June 2021

e18818

Background: While there is increasing evidence that precision cancer medicines (PCMs) can be more effective than “one-size-fits-all” (OSFA) oncology medicines, questions persist as to their cost, availability, and overall patient benefit. We determined whether using a PCM approach to medicines discovery/development delivers medicines within cost constraints of health systems. R&D costs of developing a medicine are a subject of debate, with average estimates ranging from $314 million (M) - $2.8 billion (B). Methods: Data on oncology medicines approved (2011-2020) by the US Food and Drug Administration (FDA) were analyzed, employing two approaches to estimate R&D costs to bring the medicine to market: (i) Securities and Exchange Commission (SEC) data were compiled from 10-K and 10-Q financial performance filings on the medicine’s development cost through its R&D lifetime. (ii) Employing a base figure of $100,271 (the estimated cost per patient in a phase III clinical trial), costs were calculated, based on data from clinicaltrials.gov. Trial data were split into clinical trial phases and probability of trial success calculated, along with preclinical costs. Cost-of-capital (CoC) approach was applied and if appropriate an orphan drug tax credit (ODTC) was subtracted from the total. Results: 19 PCMs and 11 OSFA oncology drugs listed by the National Cancer Institute which had complete data were analyzed from 22 companies (Table). Initial costs from SEC data suggest a 50% reduced development spend for PCM, ($605M; range = $181M-$1.1B) (Clinical Trial Modelling Analysis: $604M ($63M-$2.29B)), compared to an OSFA oncology drug development spend ($877M; $333M-$3.34B) (Modelling Analysis: $597M ($41M-$1.64B)). Once preclinical costs were added total R&D costs capitalized and ODTC subtracted, there was an 83% increase in costs, from $2.44B ($614M-$5.23B) (Modelling Analysis: $3.1B ($209M-$11.52 B)) for PCMs to $4.46B ($1.59-$14.9B) (Modelling Analysis: $3.92B ($282-$12.74B) for OSFA oncology drugs. SEC data are more accurate, as they capture real data, rather than modelling assumptions. Conclusions: Our results provide an estimate of the R&D spend required to bring an oncology medicine to market. R&D cost of a PCM is below the top range of prior estimates published, while R&D cost of an OSFA oncology medicine is almost twice the cost of a PCM, emphasizing the potential for PCM treatments to deliver care at greater value to patients and health systems.[Table: see text]
Prevalence-adjusted trends in U.S. healthcare spending on colorectal cancer, 1996-2016.
Authors: Stukalin Igor , Ahmed Newaz Shubidito , Fundytus Adam Michael , Singh Siddharth , Ma Christopher
Published: June 2021

e18819

Background: Colorectal cancer is rising in prevalence and associated with high healthcare costs. We estimated trends in the US healthcare spending in patients with colorectal cancer between 1996 and 2016. Methods: We used data on national healthcare spending developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. Corresponding US age-specific prevalence of colon cancer was estimated from the Global Burden of Diseases Study. Prevalence-adjusted, temporal trends in the US healthcare spending in patients with colorectal cancer, stratified by age groups ( < 20, 20-44, 45-64, >65) and by type of care (ambulatory, inpatient, emergency department, pharmaceutical prescriptions, nursing care and government administration) were estimated using joinpoint regression, expressed as annual percent change (APC) with 95% confidence intervals. Results: Overall, annual US healthcare spending on colorectal cancer increased from $8.85 billion (95% CI $8.17 billion, $9.53 billion) in 1996 to $10.5 billion (95% CI $9.35 billion, $11.7 billion) in 2016, with total costs increasing by 0.9%/year (95% CI 0.1%, 1.6%). After adjusting for colorectal cancer prevalence, the absolute per capita spending decreased from $8848 to $8427 and there has been no significant change over time (APC 0.3%, 95% CI, -0.2%, 0.8%). However, spending in patients > 65 decreased significantly by 1.3%/year (95% CI -2.2%, -0.5%). Inpatient care was the largest contributor to total colorectal cancer-related expenditures: in 2016, 65.9% (95% CI 59.5%, 71.0%) and 19.7% (95% CI 14.8%, 25.8%) of the total cost were spent on inpatient care and ambulatory care, respectively. Between 1996-2016, increases in the price and intensity of care (defined by the cost per encounter) was the largest positive driver of changing healthcare spending, accounting for $5.02 billion ($2.60, $7.33 billion). Conclusions: After adjusting for rising prevalence, US healthcare spending on colorectal cancer has not changed significantly since 1996, while the per capita cost continues to decrease, primarily in patients > 65 years old. Inpatient care accounts for the majority of colorectal cancer-related expenditures.
U.S. budget impact analysis of biosimilar versus originator intravenous rituximab for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
Authors: James Elizabeth , Trautman Holly , McBride Ali , Choudhry Azhar , Thompson Stephen
Published: June 2021

e18820

Background: Rituximab-abbs is an anti-CD20 monoclonal antibody and an important immuno-oncology agent for the treatment of B-cell malignancies NHL (diffuse large B-cell lymphoma [DLBCL] and follicular lymphoma [FL]) and CLL. It is also indicated for patients with RA, GPA, and MPA. Rituximab-abbs was the first rituximab biosimilar approved in the US and is expected to reduce drug acquisition costs. This budget impact model (BIM) estimated the impact of replacing a share of originator rituximab (IV-R-REF) use with rituximab-abbs (IV-R-BIOSIM) for NHL (DLBCL and FL), CLL, RA, GPA, and MPA. The objective was to project incremental annual cost differences between IV-R-BIOSIM and IV-R-REF for a hypothetical 1-million-member US healthcare insured (Medicare) population. Methods: An illustrative BIM estimated changes in 1-year drug and administration costs for an increased IV-R-BIOSIM uptake from 17.5% to 22.0%. Values for epidemiology, market share distribution, drug dosing, administration, and costs were derived from scientific literature, product labels, and publicly available cost resources. Dosing was based on a mean patient body surface area of 1.8 m2. Annual dose counts per patient were: 10 untreated FL with maintenance; 8 untreated FL (without maintenance), relapsed/refractory FL, or untreated DLBCL; 6 CLL, and 4 for RA, GPA, or MPA. All treatments were assumed to infuse over 3 hours. Drug acquisition and administration costs were from 2020 Average Sales Price pricing file and Centers for Medicare and Medicaid Services Physician Fee Schedule. Patient cost share was based on 2020 Medicare Part B 20% cost-share for office visits and drug products. Univariate sensitivity analyses were conducted. A scenario analysis was performed to project 2-year costs for extended FL maintenance treatment. Results: Estimated total annual plan incremental savings for a 1-million-member payer after the utilization shift were $312,379, equating to $0.31 per enrolled member per year (PMPY). Per-patient incremental drug cost savings with IV-R-BIOSIM for 1-year were $5,474–$12,924 (Table). The model was most sensitive to IV-R-REF cost and proportion of patients with RA. Conclusions: This analysis estimated annual savings of over $310,000 ($0.31 PMPY) for a 1-million-member US payer following a 4.5% utilization shift from IV-R-REF to IV-R-BIOSIM, demonstrating that IV-R-BIOSIM may confer considerable economic benefits vs originator rituximab.[Table: see text]
Novel elements of value in the context of oncology.
Authors: Kamal-Bahl Sachin , Puckett Justin , Singh Amitabh , Willke Richard
Published: June 2021

e18823

Background: Over the past decade, perhaps no single area of the health sector has seen as much groundbreaking innovation as pharmaceuticals. This has been especially true in oncology, where promising curative treatments have been initially celebrated by the media only for access and cost challenges to limit their impact. A narrative has emerged that many of these breakthroughs are not priced according to the value they provide. This thinking has been reinforced by traditional approaches to cost-effectiveness analysis (CEA) that fail to incorporate critically relevant dimensions of value for innovative oncology therapies. What might a broader conception of value in oncology look like? To answer that question, this study reviews oncology-specific considerations when assessing elements of value. Methods: We first review the background on the nature and development of quality-adjusted life years (QALYs) as a part of cost-effectiveness analyses and some of their key limitations. This is followed by a review of “novel” elements of value, which capture specific aspects of patient and societal preferences not included in QALYs, and their applicability to oncology, including discussion on areas where further thought and research might be needed. We conclude with a potential checklist of novel elements of value that should be considered when designing value assessment strategies for products in oncology. Results: Key novel value elements not captured in QALYs under traditional CEA that can be relevant for oncology include value of hope (for a cure), value of insurance (reducing health and financial risk), value of treating very severe diseases, and, real option value (for treatments extending survival enough to allow the option of future cures). The novel value elements of reduced diagnostic uncertainty and the value of knowing are also directly relevant for oncology products with companion diagnostics. Other relevant novel value elements within the context of oncology include scientific spillovers and equity. Few studies have measured these value elements with applications in oncology. Conclusions: Our key takeaways include: (1) since cancer is often a severe disease that is expensive to treat, the potential for novel value elements to be important in economic evaluations of oncology products is high; (2) while some elements of value have been explored in specific economic evaluations, there has been limited adoption of novel elements of value in oncology; (3) the conceptual justification for use of novel value elements in oncology is strong, but standards for their measurement are evolving and further experience with their use would be beneficial; and (4) given the lower prioritization of many of them from the payer perspective, barriers to payer acceptance also seem significant, implying attention must also be paid to establishing the relevance of those elements to payer decision-making.
Factors associated with off-label (OL) drug use in oncology: The role of cost and financing in a universal healthcare system.
Authors: Gordon Noa , Goldstein Daniel A , Tadmor Boaz , Stemmer Salomon M. , Greenberg Dan
Published: June 2021

e18825

Background: In recent years, OL use in oncology has become widespread, with estimates ranging up to 50-75% of all prescriptions. Most OL use is not publicly reimbursed within universal healthcare systems. We aimed to characterize the financing sources of OL use and to identify predictors for forgoing such treatment. Methods: We studied 708 oncology OL prescription requests submitted for approval to the Institutional Drug Committee in Rabin Medical Center, a large tertiary center in Israel, between January 2016 and December 2018. We included only requests for patients that were alive for more than 60 days following prescription approval. For each indication we extracted the level of supporting evidence at the time of prescription (sufficient, limited, inadequate). We also examined patients’ disease and sociodemographic properties, treatment costs, and financing sources. We used univariable logistic regression to ascertain these variables’ effects on actual OL drug initiation. We then used multivariable logistic regression to explore predicting factors for drug initiation. Results: The median monthly cost of a planned OL treatment was ILS39,928 (approximately US$ 11,500). Approximately one third (31%) of the treatments did not have a financing source at the time of request approval. The primary financing sources were patient access plans (30%) and private health insurance (25%). Of 708 approved OL requests, only 583 (82.3%) treatments were initiated. The proportion of requests that were eventually initiated was higher in the metastatic versus adjuvant setting (84.9% vs. 76.5%; p= .008). The estimated median OS for metastatic patients was 9.9 months, significantly higher in patients that did initiate treatment versus patients that did not (10.4 vs. 7.2 months; p= .048). Although not significant, median costs of initiated treatments were higher compared to treatments that were not (ILS41,686 vs. ILS24,670). Prescriptions for the metastatic setting and immunotherapy as well as ones with sufficient evidence had higher odds for treatment initiation (OR = 1.73; p= .007, OR = 1.69; p= .013 and OR = 1.62; p= .016). Prescriptions with limited supporting evidence and with no planned financing source had lower odds for treatment initiation (OR = 0.59; p= .012, OR = 0.37; p< .0005). A multivariable logistic regression showed that if no financing plan was in place at the time of request, there was a 2.5 times higher likelihood of not initiating the treatment (OR = 2.5; p< .0005). Conclusions: While OL recommendation is widespread and institutional approval is granted, a substantial proportion of treatments are not initiated. Although cost was not associated with treatment initiation, having a planned financing source was a strong predictor for OL treatment initiation. This study elucidates the financing sources of OL treatments in a universal healthcare system and identifies access barriers.
U.S. budget impact (BI) model for selinexor, bortezomib, and dexamethasone (XVd) for the treatment of patients with previously treated multiple myeloma (MM).
Authors: Dolph Mike , Tremblay Gabriel , Leong Hoyee
Published: June 2021

e18839

Background: Despite advances in the treatment of MM, prognosis remains poor for most patients due to its refractory nature. In a phase 3 study, a once-per-week regimen of XVd showed a novel, effective, and convenient option for patients with previously treated MM. This study was conducted to estimate the projected budget impact (BI) of XVd in patients with previously treated MM from the perspective of a third-party payer and Medicare in the US. Methods: The introduction of XVd as a treatment option for patients with previously treated MM compared to the status quo (i.e. without the introduction of XVd) was considered from a private third-party US payer and a Medicare perspective in one-year increments for the first 3 years. The model assumed market uptake of 5.9%, 7.2%, and 7.7% at years 1, 2 and 3, respectively. Total annual treatment costs (2020 US dollars [USD]) were calculated as the sum of drug costs, the costs of treating serious treatment emergent adverse events (grade ≥3), ongoing best supportive care costs, and mortality costs. Results: In the base-case analysis for a private third-party payer plan (1,000,000 members), 3 to 4 patients were projected to receive XVd out of 47 to 49 eligible patients each year. The absolute BI (Millions, USD) of including XVd from a private third-party payer plan perspective was $0.06, $0.07, $0.08 and $0.22 for years 1, 2, 3, and overall, respectively. The relative BI of including XVd was 0.33%, 0.40%, 0.43%, and 0.38% for years 1, 2, 3, and overall, respectively. This translated to a per member per month (PMPM) budget impact of $0.005, $0.006, $0.007, and $0.006 (USD), for years 1, 2, 3, and overall, respectively. In the base-case analysis from the Medicare perspective (59,499,015 members), 1,361 to 1,808 patients were projected to receive XVd out of 22,892 to 23,425 eligible patients each year. From a Medicare perspective, the absolute BI (Millions, USD) of including XVd was $29.68, $36.62, $39.42 and $105.72 for years 1, 2, 3, and overall, respectively. The relative BI of including XVd was 0.33%, 0.40%, 0.43%, and 0.38% percent for years 1, 2, 3, and overall, respectively. This translated to a PMPM budget impact of $0.041, $0.051, $0.054, and $0.049 (USD), for years 1, 2, 3, and overall, respectively. One-way sensitivity analyses showed general consistency with the base-case findings. Conclusions: Understanding the potential BI of new therapies in MM is vital for decision makers to manage spending and assess the value of treatments. The introduction of XVd presents a small and manageable BI for a third-party US payer and Medicare.
Economic impact of compassionate use of medicines.
Authors: Jommi Claudio , Pantellini Federico , Stagi Lisa , Cavazza Marianna
Published: June 2021

e18840

Background: The economic impact of clinical trials in the perspective of trial sites has been already investigated. Instead, there is no evidence on the economic net benefit of compassionate use programs for medicines (CUP). This research aims to fill the information gap, investigating the economic consequences of 8 CUP in Italy carried out from May 2015 to December 2020 in the hospitals’ perspective. These programs concern five cancer medicines (alectinib, atezolizumab, cobimetinib, polatuzumab vedotin, trastuzumab emtansine TDM-1), for a total of 8 programs. Methods: Economic net benefit includes avoided costs for standard of care (SoC) the patient would have received if he/she has not joined the CUP and costs not covered by the pharmaceutical industry and sustained by the hospital hosting CUP. The latter include costs of adverse event (only severe sides effects generating hospitalisation and ascribed to medicines used in CUP), combination therapies and diagnostic procedures not covered by the sponsor. SoC costing relied on publicly available estimation. Adverse events and diagnostic procedures were retrieved from the CUP and monetized using the relevant fee for episode. Results: 1635 cancer patients were treated in eight CUPs. The SoC mean cost per patient ranges from €13355 to €28098 for all cancer drugs. The total cost of the SoC ranges from €21.8 - €45.9 million. The mean cost per patient covered by hospitals hosting CUP was equal to €2732 for cancer drugs, with a total cost of €4.5 million. The net economic benefit ranges from €17.4 million to €41.5 million for cancer treatments. Conclusions: Despite its limitations this paper illustrates for the first time the net economic impact of CUP in oncology patients in the perspective of payers. Additional evaluations are ongoing to better understand the overall effects of CUP implementation, i.e. the economic value of the comparative benefit profile of medicines used in CUP versus the SoC, including potential effects on indirect costs.
Prospects of off-label (OL) drug use in oncology: Identifying predicting variables for registration and universal healthcare reimbursement.
Authors: Gordon Noa , Goldstein Daniel A , Tadmor Boaz , Stemmer Salomon M. , Greenberg Dan
Published: June 2021

e18842

Background: Many cancer drugs used OL, eventually complete clinical development and are registered and reimbursed, while others are not. We aimed to describe OL indications' registration and reimbursement prospects in a universal healthcare system and identify groups of treatments that remain OL longer. Methods: We studied 612 OL oncology prescription requests for 115 unique indications and 29 drugs. All requests were approved by the Institutional Drug Committee in Rabin Medical Center, a tertiary center in Israel, between January 2016 and December 2018. OL indications were not registered by the Israeli Ministry of Health (MOH) and were not included in the Israeli National List of Health Services (NLHS) for reimbursement at the time of prescription. Additionally, 459 requests for 100 indications were not approved by the FDA at the time of prescription. We explored the subsequent regulatory and reimbursement milestones in the timeline following each prescription. We identified three temporal events: FDA indication approval, MOH indication registration, and NLHS indication inclusion of reimbursement. We then defined three time-to-event variables from the OL prescription to each of the three milestones. We applied Kaplan-Meier analysis and multivariable Cox regression to identify drug and indication properties, which are predictors for registration and reimbursement. Results: With a median follow-up of 34.5 months, 10.4% of indications were eventually registered in Israel, and 6% were included in the NLHS. 7% of non-FDA approved indications were subsequently approved. For MOH registration, positive predictors were immunotherapy, sufficient evidence (ESMO-MCBS A-B, 5-4), and a patient access program at the time of prescription (HR = 21.99; p< .0005, HR = 3.4; p= .02 and HR = 2.73; p< .0005, respectively). Negative predictors were metastatic setting and lung and gastrointestinal (GI) cancers (HR = 0.42; p= .002, HR = 0.17; p= .001, and HR = 0.24; p= .043, respectively). For NLHS inclusion, positive predictors were immunotherapy, sufficient evidence, and an access program (HR = 9.03, HR = 6.24, and HR = 2.56, respectively, all p< .0005). Negative predictors were lung and GI cancers and orphan disease designation (HR = 0.07; p= .002, HR = 0.14; p= .021, and HR = 0.13; p= .009, respectively). For FDA approval, positive predictors were immunotherapy, sufficient evidence, and a patient access program (HR = 12.11; p< .0005, HR = 4.34; p= .002, and HR = 2.25; p= .001, respectively). Negative predictors were metastatic setting, lung cancer, and orphan disease (HR = 0.43; p= .003, HR = 0.25; p= .006, and HR = 0.08; p= .018, respectively). Conclusions: Few OL indications are subsequently approved and reimbursed, usually due to clinical futility and insufficient evidence. However, we identified factors related to lack of initiative for further clinical development and registration.