bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining clinical trial eligibility for oncology patients with human immunodeficiency virus (HIV): A global cross-sectional analysis.
Authors: Abdullahi Umar , Shaya Sammy , Dinizulu Habana , Sampey Emily , Appleton David , Concannon Matthew , Graham Donna M.
Published: June 2023

6554

Background: People Living with HIV (PLWH) are at higher risk of developing cancer, and malignancy is the most common cause of death in PLWH in the USA . In 2017 a joint research statement by the American Society of Clinical Oncology and Friends of Cancer Research (ASCO-FCR) examined trial inclusivity, stating PLWH should not be excluded from clinical trials due to HIV positivity alone without justification. It also provided guidance for designing trial inclusion criteria using CD4 count, use of antiretroviral therapy (ART), ART-related drug interactions and HIV-associated complications. To review incorporation of ASCO-FCR recommended wording and current compliance, we examined global eligibility for PLWH in clinical trials. Methods: Clinicaltrials.gov was searched on 15 Nov 2022 for open and recruiting trials worldwide, using terms ‘advanced cancer’ and ‘interventional’. Trials lacking systemic treatment were deemed non-evaluable. Evaluable studies’ eligibility criteria were manually reviewed for specific criterion excluding PLWH or diagnosis/history of immunodeficiency (outright exclusion). Therapy type and study phase were captured and their relationships to outright exclusion were significance tested using odds ratios (OR) with 95% confidence intervals (CI). Results: The search rendered 2388 evaluable clinical trials. Eligibility criteria outrightly excluded PLWH in 1194 (50%) , of which 1113 (93%) were early phase trials (Phase 0-2). 206 evaluable trials (8.6%) permitted inclusion of PLWH aligned with ASCO-FCR guidance, including 3 (0.1%) with a cohort for PLWH. AIDS-defining illness was an exclusion criterion in 27 trials (1%), and specific interactions to ART in 10 (0.4%). Early phase trials had a significantly higher likelihood of outright exclusion of PLWH when compared with late phase trials (OR 2.98; 95% CI 2.16-4.11, p<0.0001). Trials investigating immunomodulatory agents were more likely to outrightly exclude PLWH than those investigating other drug classes (OR 1.60; 95% CI 1.36-1.88, p<0.0001). Criteria which may implicitly exclude PLWH were identified, including 204 (8.5%) citing active/chronic/severe infection, 189 (7.9%) listing CYP and P-gp interaction criteria and 3 (0.1%) "immunodeficiency". Conclusions: Despite adequate time to incorporate, most currently recruiting oncology clinical trials do not use ASCO-FCR guidance for including PLWH. Half of evaluated trials excluded PLWH without reason. Early phase and immunotherapy trials were significantly more likely to exclude PLWH without exception, despite data to support immunotherapy use for PLWH. Covert inclusionary barriers exist in criteria that lack HIV-specific guidance, and this may further exclude PLWH. Consideration of recommendations and guidance in eligibility criteria for oncology trials is critical to address current inequities in care for PLWH and cancer.
The patient experience of prior authorization for cancer care: Anxiety, delays, and the erosion of trust.
Authors: Chino Fumiko , Baez Alexandra , Elkins Ivy Beth , Aviki Emeline Mariam , Thom Bridgette
Published: June 2023

6561

Background: Prior authorization (PA) requires healthcare providers to obtain pre-approval from insurance for medical care. While PA is intended to promote evidence-based standards and reduce unnecessary care, it requires clinicians and patients to navigate an often-complex approval process. Delays or denied care can be particularly problematic for patients with cancer and their experience with PA remains unexplored. Methods: Social media recruitment enrolled adult cancer patients with a self-reported personal experience with PA to an anonymous online survey of investigator-designed questions on their experience. Descriptive statistics and univariate tests characterized survey responses, and multivariable analysis, controlling for age, diagnosis, race/ethnicity, and education, assessed associations with healthcare and insurance trust and delays in care. Results: 178 patients completed the survey; they were mostly women (90%), non-Hispanic white (84%), college graduates (81%), young [18-39 (42%), 40-54 years old (34%)] with private insurance (86%). PA was most frequently required for imaging (71%), IV chemotherapy (48%), surgery (47%), radiation (34%). Most care was ultimately given as recommended (58%); however, 20% of respondents didn’t receive recommended care due to delays or denials, and 9% received recommended care but paid out-of-pocket. PA delayed 69% of care, with 51% of patients noting a delay ≥2 weeks. Delays did not vary by demographic, clinical, insurance, or treatment factors (all p > .05). 67% of patients had to personally get involved in the PA process by either calling their insurance (53%) or filing an appeal (25%); 20% of patients and/or their caregivers spent ≥11 hours dealing with PA issues. Overall PA experience was rated as “bad” (40%) or “horrible” (32%) for most respondents. Self-reported PA-related anxiety was significantly higher than self-reported baseline anxiety (mean = 74 vs mean = 37, 0-100 scale, t = 16.6, p < .001) and was significantly correlated with time spent on PA (ρ = .16, p = .04) and overall PA experience (ρ = .34, p < .001). While 18% felt PA made them trust their cancer team less, 89% said it made them trust their insurance company less, and 83% said it made them trust the healthcare system less. Patient involvement in the PA process (vs. healthcare team handling) was associated with higher-than-expected trust in their cancer team (χ2= 19.6, p < .001), and increased odds of distrusting their insurance company (β = 5.7, 95% CI: 1.8,17.6) and distrusting the healthcare system (β = 3.2, 95% CI: 1.3,7.9). Having to file appeal was associated with 2.9 increased odds (95% CI: 1.2,7.2) of experiencing a delay in care. Conclusions: PA practices may substantially delay care for patients with cancer increasing anxiety and eroding trust in healthcare. Streamlining the PA process could both allow optimal quality of care and improve the patient experience with cancer care.
Just ASK: A quality improvement project to enhance smoking assessment and treatment.
Authors: Warren Graham W. , Ostroff Jamie S. , Mullett Timothy , Adsit Robert , Burris Jessica , Darville Audrey , Fiore Michael C. , Hahn Ellen , Kirstein Laurie , McCarthy Danielle , Nelson Heidi , Reilly Eileen , Shelton Rachel C , Tong Elisa
Published: June 2023

6571

Background: Persistent smoking after cancer diagnosis causes adverse clinical outcomes. ASCO and other organizations view smoking assessment and treatment as indicators of high-quality cancer care. Yet, adoption of clinical practice guidelines like the 3As (Ask, Advise and Assist) for smoking assessment and treatment has been slow and inconsistent in cancer care settings. Methods: Led by the American College of Surgeons Cancer Programs’ Commission on Cancer (CoC) and National Accreditation Program for Breast Centers (NAPBC), the “Just ASK” national quality improvement project focuses on enhancing smoking assessment and treatment in cancer care settings. All CoC/NAPBC programs (n~2000) were invited to participate, which consisted of educational webinars, online resources, and 3 online surveys (baseline, 6- and 12-month) collecting information on smoking assessment and treatment practices, plus other variables (e.g., organizational priority, implementation barriers). Program participation was incentivized by fulfillment of accreditation standards. Results: In total, 776 programs (731 CoC, 45 NAPBC), participated. At baseline, most programs strongly endorsed the importance of addressing smoking within cancer care and the majority of programs reported routinely assessing smoking (90%) and advising all patients reporting current smoking to quit (71%). However, routine delivery of evidence-based smoking cessation assistance (e.g., quitline referral, cessation medications, counseling services) was low (all < 30%). Program retention was excellent (91%). As shown in the table, the 12-month follow-up revealed marked improvements in evidence-based Ask, Advise and Assist, practices. Conclusions: At enrollment, the importance of addressing smoking was evident and high rates of smoking assessment were reported. At 12-month follow-up, marked improvement was reported in all quality indicators of the 3As. These findings guided the sharing of strategies for improving patient assessment, clinical workflow and documentation. Suboptimal delivery of smoking cessation assistance persisted despite overall improvements, which highlight persistent challenges and opportunities for implementing smoking assessment and treatment in cancer care settings. [Table: see text]
Incidence of infusion related reactions of daratumumab-hyaluronidase-fihj: Pre-post intervention study of premedication omission.
Authors: Padmaraju Kashyap , Kelly Kaitlin , Jakubowiak Andrzej J. , Derman Benjamin Avi
Published: June 2023

6574

Background: Daratumumab-hyaluronidase-fihj subcutaneous (Dara-SQ) is utilized frequently in the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Initially approved as an intravenous formulation, daratumumab (Dara-IV) showed significant infusion related reactions (IRRs), requiring premedication (acetaminophen, diphenhydramine, dexamethasone, and some add montelukast) prior to each dose. Dara-SQ was shown to be noninferior to Dara-IV with significantly fewer IRRs. Despite the reduced IRR risk, indefinite premedication is also recommended in the package insert for Dara-SQ. Given that IRRs are rare after the first dose of Dara-SQ and premedication extends the time for patients in an infusion center, we investigated whether premedication may be safely omitted after the first cycle. Methods: This pre-post interventional quality improvement study included all patients aged 18 years or older diagnosed with MM or amyloidosis that received at least one dose of Dara-SQ between July 1st, 2020 – December 31st, 2022. Omission of premedication (excluding dexamethasone) after four doses of Dara-SQ was introduced June 1st, 2022. The pre-interventional arm followed standard of care with premedication continued (Arm 1) and post-interventional arm included patients with premedication omitted after fourth dose (Arm 2). Patient demographics, prior therapy, Dara-IV exposure, and premedication usage were collected to evaluate the primary endpoint: incidence of IRR after premedication omission. Secondary analysis included any IRR prior to intervention, timing of reaction, reaction management, and post-reaction management. Results: A total of 102 patients (63 in Arm 1 and 39 in Arm 2) were included in the study, with a median age of 69 (38-86) years old; 52% African American and 54% male. IRR prior to fourth dose occurred in 1.6% (1/63) for Arm 1 vs. 5.1% (2/39) for Arm 2 [ p= 0.6], Dara-IV exposure was 52.4% (33/63) in Arm 1 vs. 10.2% (4/39) in Arm 2 [ p= 0.02], and indication was newly diagnosed MM in 21% (13/63) of Arm 1 vs. 41% (16/39) of Arm 2 [ p= 0.03]. For the primary objective, there were zero reactions in both arms. All three reactions prior to fourth dose occurred after the first dose of Dara-SQ, with a median time to reaction of 4.8 hours. These were all grade 2 per CTCAE v5.0, with all patients discharged home after reaction, and all patients received subsequent Dara-SQ without issues. For the two reactions prior to fourth dose in Arm 2, premedication was omitted after 6 doses in one patient and 8 doses in the other with no further issues on subsequent doses. Estimated therapy time saved was 194 hours, with an estimated savings of $145,500 thus far. Conclusions: IRRs to Dara-SQ occur early, are rare, and mild in course. Omitting premedication after a minimum of four Dara-SQ doses is safe and carries substantial time savings for patients and infusion centers.
The association of HIV and other risk factors with triple-negative breast cancer in South African women.
Authors: Dubner Jacob , Neugut Alfred I. , Joffe Maureen , O'Neil Daniel , Ayeni Oluwatosin , Chen Wenlong Carl , Buccimazza Ines , Čačala Sharon , Stopforth Laura , Farrow Hayley , Nietz Sarah , Phakathi Boitumelo , Jacobson Judith , Crew Katherine D. , Ruff Paul , Cubasch Herbert , Pumpalova Yoanna S
Published: June 2023

6583

Background: Breast cancer (BC) mortality in South Africa (SA) is double that of the United States. The aggressive triple-negative breast cancer (TNBC) subtype comprises 20.9% of BC cases among Black women in Southern Africa. SA has the second highest HIV prevalence worldwide, but if and how HIV affects the risk of developing TNBC is not well understood. Methods: Using the South African Breast Cancer and HIV Outcomes (SABCHO) prospective cohort of newly diagnosed BC patients from six public hospitals in SA, we evaluated the association of HIV with risk of TNBC relative to other BC subtypes. We developed multivariable logistic regression models to test for this association while adjusting for key demographic and reproductive risk factors. Results: Of 3,883 women with BC, 16.4% had TNBC and 23.0% were HIV-positive. The overall median age of BC diagnosis was 55 years. Among HIV positive patients, the median age of BC diagnosis was 45 years, without a difference between TNBC and non-TNBC cases (p = 0.244). Only 7.2% of women were nulliparous (4.6% in TNBC and 7.6% in non-TNBC subgroups). Of women who had at least 1 full-term pregnancy, 11.2% did not breastfeed, without a difference between TNBC and non-TNBC cases (p = 0.292). In our final multivariable logistic regression model, HIV-positive status was associated with increased risk of TNBC relative to non-TNBC (OR: 1.40; 95% CI: 1.12-1.74, compared to HIV-negative with BC). Parity without breastfeeding was also associated with increased risk of TNBC relative to non-TNBC (OR: 1.72; 95% CI: 1.07-2.84, compared to nulliparous with BC). HIV status and the combined parity/breastfeeding variable had no statistically significant interaction. In exploratory analyses, measures of HIV control at time of BC diagnosis were not associated with BC subtype. Conclusions: In this large prospective case-only study conducted in SA, we found that women living with HIV were more likely than HIV-negative women to have TNBC (relative to other BC subtypes), regardless of the extent of HIV control. Whether this relationship is mediated by immune mechanisms or other factors should be the focus of future research. Our findings highlight the importance of rigorous BC screening and early detection among HIV-positive women given their increased relative risk of developing TNBC. [Table: see text]
Real-world analysis of cardiac, gastrointestinal, and hematologic toxicities between commonly used antiemetics in everyday oncology clinical practice.
Authors: Beedupalli Kavitha , Ananthaneni Anil , Findakly Dawood
Published: June 2023

6587

Background: Antiemetics are highly effective in chemotherapy-induced nausea and vomiting. We utilized Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate adverse events (AEs) caused by selected antiemetics commonly used in outpatient oncology practice. Methods: We analyzed the FAERS database to assess the cardiac, gastrointestinal (GI), and hematologic AEs for metoclopramide, olanzapine, ondansetron, and promethazine from 2013 through 2022. The disproportionality signal was analyzed by calculating Reporting Odds Ratio (ROR) with a 95% confidence interval (CI)—considered significant when the lower limit of 95% CI was > 1. Results: A total of 20,302 AEs were identified, out of which 8,135 (40.1%) were cardiac—arrhythmia and QTc prolongation; 8,656 (42.5%) were GI—nausea/vomiting, constipation/diarrhea, abdominal pain/discomfort, and dyspepsia; and 3,511 (17.3%) were hematologic—leukopenia, thrombocytopenia, anemia, and pancytopenia. Compared to other antiemetics, promethazine and olanzapine had higher cardiac and hematologic AEs, respectively, whereas metoclopramide, followed by ondansetron had higher GI AEs (Table). Conclusions: Antiemetics are readily available and effective, yet the preference for a particular drug or drug combination varies. Our study highlights selected antiemetics AEs in order to help individualize treatment for this often challenging and frequently encountered entity. [Table: see text]
Real-world evidence to inform clinical insights on tissue-agnostic approvals of therapies.
Authors: Sledge George W. , Yoshino Takayuki , Xiu Joanne , Helmstetter Anthony , Klimov Sergey , Gilg Brady , Oberley Matthew James , Radovich Milan , Abraham Jim , Spetzler David
Published: June 2023

6589

Background: Many tissue-agnostic (TA) approvals were based on clinical trials with limited patient numbers without covering all tissue types (TT), raising the question of whether these indications were truly tissue agnostic. Real world evidence (RWE) offers an opportunity to investigate TTs not included in clinical trials/studies to answer this question. Herein we investigate the seven TA approvals to date in a large real world database and report clinical outcomes. Methods: A total of 186,581 tumors from over 35 TTs tested with comprehensive molecular profiling including NextGen sequencing of DNA and RNA were investigated for TA alterations (TMB-High (≥10 mutations/MB), MSI-H/MMRd, BRAF V600E mutations and NTRK1/2/3/RET fusions) at Caris Life Sciences (Phoenix, AZ). Time-on-treatment (TOT) from RWE was obtained from insurance claims and calculated from treatment start to finish. Kaplan-Meier estimates were calculated for molecularly defined patient cohorts. Significance was determined as p values of <0.05. Results: Among all tumors, 21.2% carried at least one TA alteration, 17.2%, 3.4% and 0.6% had 1, 2 or 3 alterations, respectively. TMB-H in 18.7%, MSI-H/dMMR was seen in 3.9%, BRAF V600E in 2.8% of tumors, NTRK1/2/3 and RET fusion seen in 0.16% and 0.23%. TA alterations were most prevalent in BCC (86%) & SCC (82%) of skin, MEL (71%), THCA (51%) and NSCLC (44%) and least in liposarcoma (0), meningioma (0.7%) and GIST (1.4%). Among tumors treated based on TA indications, substantial variability of TOT among TTs was observed (see table). Looking at TTs included (INC) and not included (nINC) in KEYNOTE-158 and other studies for TMB-H and pembro, median TOT for nINC was similar to INC (N=242 vs 2322, 6.1 m vs 6.3 m, p = 0.55). Nevertheless, statistically significant differences in median TOTs were seen across nINC when comparing TMB-H vs. TMB-L (6.1m vs. 2.9m, HR: 0.58 [95% CI: 0.50-0.67], p<0.001) and in a subset of 838 MSS tumors (4.9m vs. 2.8m, p<0.001). Conclusions: RWE data adds substantially to our understanding of the demographics of TA indications and suggests that some TA treatment benefits may be tissue-specific. Recent TA indications will require further accumulation of cases to draw meaningful conclusions regarding whether TA indications are, in fact, tissue agnostic. [Table: see text]
Real-world behavioral restrictional practices of cancer patients (pts).
Authors: Shachar Eliya , Moisa Noy , Peleg-Hasson Shira , Safra Tamar , Wolf Ido , Vorobiof Daniel A.
Published: June 2023

6592

Background: Quality of life (QoL) assessments do not measure pts’ ability to maintain normal daily activities during cancer therapy. Misbeliefs might promote avoidance of activities perceived as dangerous, compromising pts QoL. We examined the daily practices of actively treated pts with cancer. Methods: A locally validated questionnaire at the Tel-Aviv Sourasky Oncology Division was distributed internationally using the Belong.life social and professional digital health platform. We examined real-world pts reported practices, provided voluntarily and anonymously. The survey consisted of 15 questions, including demographic, clinical, behavioral parameters and sources guiding and supporting pts practices. Independent clinical and demographic variables were analyzed. Statistical analysis was performed, and a multivariate logistic regression was conducted to identify factors predicting restrictive behaviors. Results: The study population comprised 1,395 pts receiving active cancer therapy, reporting their outcomes from the Belong digital platform. Most respondents were from the United States (1082, 77.70%) and Israel (223, 16%), over the age of 40 (1309,93.8%),and female (987, 70.75%). Most common tumor types were breast (394,28.24%) and gastrointestinal cancers (199,14.26%). The majority of pts (1,005,72.88%) reported on at least 1 adopted limitation in daily activities, and 305 (21.86%) maintained more than half of these constraints. Daily life restrictions included avoiding sun exposure (779, 57.83%), international travel (417, 33.33%), indoor public places (malls, etc) (431, 33.13%), hair dyeing (271, 22.72%), domestic tourism (284, 21.93%), contact with friends and family (231, 17.69%), children and grandchildren (202, 16.33%), outdoor public spaces (190, 14.62%), and contact with pets (135, 10.41%). Multiple sources were implicated by the pts as guiding their behavior, with the most common being health-care professionals (951, 65.95%), followed by both non-medical authorities and health-care team (320, 22.19%), and non-medical advisors, including internet, pts forums, partners, friends, and family (171, 11.86%) Pts who maintained strict (≥50% of the limitations) and less strict restrictions, demonstrated no significant association between country of origin (p = 0.118), and education level (p = 0.3591). A significant association was noted between younger age (p = 0.0014), female sex (p = 0.0141) and primary cancer site (p < 0.0001), and the adoption of strict restrictions. Conclusions: The majority of pts reported compromised daily activities, which are likely attributed to misconceptions about therapy and disease, deleteriously impacting QoL, therefore, impeding their ability to continue to conduct a complete and meaningful life. These findings require development of tools examining patients’ real-daily life activity as an additional endpoint in clinical trials.
Evaluating depth of disparities in relation to relative survival rates: Analysis of SEER data.
Authors: Habib Alma , Huang Ying , Paskett Electra D. , Devarakonda Srinivas S. , Fisher James L. , Kittai Adam
Published: June 2023

6602

Background: Prior studies have identified widening survival disparities between Black vs White patients (pts) in solid tumors with higher 5-year relative survival rates (RSR), a surrogate for higher amenability to treatment (Tehranifar et al., 2009). Given major advancements in treatment for hematologic malignancies leading to higher RSR, we sought to evaluate whether disparities worsened with higher RSR, especially among Black pts compared to White pts, in the modern era of therapy. We hypothesized that racial disparities would be larger in malignancies with higher amenability, as measured by 5-year RSR. Methods: We identified first hematologic malignancies among pts ages ≥18 years diagnosed between 2009-2019 in a collection of 17 Surveillance, Epidemiology and End Results (SEER) Program registries. We treated RSR as a continuous variable. Cox proportional-hazards model was used to correlate RSR and race with overall survival (OS) controlling for other pt characteristics. The interaction between RSR and race was included in the model to test if the racial effect on OS differed at various RSR levels. Results: We identified 363,340 pts who met inclusion criteria. Median age was 66 years and 55% were male. 82% were White and 10% Black. With a median follow-up of 48 months (mos), median RSR was 68.2% and median OS was 101 mos (95% CI 100-102 mos). Black pts had a lower median RSR than White pts, 63.8% vs 68.9%, and lower median OS, 90 mos (95% CI 87-93 mos) vs 99 mos (95% CI 98-100 mos). On univariable analysis, all variables were statistically significant given the large sample size. On multivariable analysis (MVA), Black pts had a higher risk of death than White pts. The interaction between 5-year RSR and race was highly significant (p=<0.01, not shown in Table), as indicated by slightly increasing hazard ratios (HRs) reflecting Black-White survival differences with increasing RSR level (i.e., as RSR increased, Black pts had slightly worse OS than White pts) (Table). Conclusions: We hypothesized that with increasing RSR, Black-White disparities might increase, as all effective therapies which contribute to improved RSR might not be equitably available to all populations. We observed that statistically significant disparities were present across RSR levels and increased only minimally for those with hematologic malignancies with higher RSR. In conclusion, disparities are prevalent in hematologic malignancies despite the degree of amenability to treatment. [Table: see text]
The safety of seasonal influenza vaccination among patients prescribed immune checkpoint inhibitors: A self-controlled case series study using administrative data.
Authors: Grima Alicia Ann , Kwong Jeff C , Richard Lucie , Raphael Jacques , Basta Nicole , Carignan Alex , Top Karin , Brousseau Nicholas , Blanchette Phillip S. , Sundaram Maria
Published: June 2023

6606

Background: Immune checkpoint inhibitor (ICI) therapy for cancer patients carries a risk of severe immune-related adverse events (IRAEs). Since vaccines are immunomodulatory, administering seasonal influenza vaccinations to individuals on ICI therapy may exacerbate this risk. However, these vaccines provide substantial benefit to this at-risk population. As severe IRAEs are rare, previous vaccine safety studies in this population have been underpowered and have shown conflicting results. Methods: We used health administration data on adult Ontarians who initiated ICI therapy and received an influenza vaccine between January 1, 2012, and December 31, 2019. We conducted a self-controlled case series study, with a pre-vaccine control period (12-weeks post-ICI initiation to 14 days before vaccine), risk period (42 days post-vaccine), and a post-vaccine control period (until observation end). Each individual contributed a maximum of 2 years of person-time. Emergency department (ED) visit(s) and/or hospitalization for any cause was used as a surrogate measure of severe IRAE frequency. We fitted a fixed effect Poisson regression model incorporating seasonality and time to estimate incidence. Results: We identified 1133 patients who received an influenza vaccine on ICI therapy. The majority were aged ≥66 years (72.7%), male (62.8%), and had lung cancer (53.9%). A quarter (25.9%) experienced an ED visit and/or hospitalization during the observation period. The rate of ED visits and/or hospitalization per person-days in the risk and control periods were similar, with an incidence rate ratio of 1.04 (95% CI: 0.75, 1.45). Subgroup and sensitivity analyses revealed similar findings. Conclusions: Receipt of a seasonal influenza vaccine was not associated with an increased incidence of ED visit or hospitalization among adults on ICI therapy. The results from this analysis suggest no significant safety concern with administering influenza vaccines to this patient population.
An assessment of the provider financial risk impacts of adoption of biosimilars in the Medicare Oncology Care Model.
Authors: Roth Joshua A. , Chaudhry Basit Iqbal , Yue Andrew , Kelton John M. , Shelbaya Ahmed , Tran Lisa , Li Meng , Yang Jingyan
Published: June 2023

6613

Background: In 2016, Medicare launched the Oncology Care Model (OCM)—a Value-Based Payment (VBP) initiative providing per-beneficiary prospective payment to providers, and performance-based financial incentives/risks based on cost of care in 6-month ‘episodes’ vs. risk-adjusted benchmarks for cancer patients receiving chemotherapy. Oncology biosimilars may play an important role in managing financial risk in the OCM and other VBP models, but the real-world impact remains uncertain. The objective of this study was to quantify the impact of biosimilar adoption on oncology provider financial risk under the OCM using real-world data. Methods: We estimated the impact of biosimilar adoption on provider financial risk from 2019 to 2021 by modeling the methods (episode framing, pricing, & risk adjustment) of the OCM. Cancer episodes were identified from the 5% Medicare Limited Data Set (LDS). The study sample consisted of cancer treatment episodes with use of any of the following agents or their biosimilars: bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, and pegfilgrastim. Financial risk was defined as the difference in observed total cost of care vs. OCM target episode cost. The primary outcome was the difference in financial risk (expressed in nominal $USD) under observed use of reference and/or biosimilars vs. hypothetical use of 100% reference agent. Results: The study sample included 8851 6-month episodes initiating between 1/2019 and 6/2021. Biosimilar adoption resulted in a mean cost reduction of $1,020 per episode vs. hypothetical 100% use of reference agents. Biosimilar use increased markedly over the study horizon--with 24% of episodes with a biosimilar in Half (H)1 2019, increasing to 65% by H1 2021, and driven by increased use of antineoplastic (1% to 36%) vs. supportive care biosimilar agents (23% to 34%). Mean financial risk reduction grew with the rapid adoption of biosimilars over this period. The average risk reduction in episodes initiating in H1 2021 was about 10 times larger than that seen in episodes initiating in the H1 2019 ($2060 vs $201, See Table). Observed mean cost was below the OCM target cost ($48808) in H1 2021 but exceeded the target cost in all other periods (range: +$1451 to +$4966). Conclusions: From 2019 to 2021, rapid adoption of biosimilars in Medicare fee-for-service beneficiaries included in the LDS led to substantial cost savings and reduction in risk for cancer episodes evaluated under the OCM methods. Broad adoption of biosimilars is a key strategy that providers in oncology VBP models will need to consider to manage financial risk. [Table: see text]
Effects of concomitant gut-microbiome altering medications on immune checkpoint inhibitors therapy: A retrospective study.
Authors: Singh Rohit , Batra Akshee , Schuetz Samantha R , Gandler Helen , Barker Jacob , Devine Derek , Rehman Hibba tul , Alejos David , Ahmed Shahid Sattar
Published: June 2023

6617

Background: In cancer patients, gut microbiota influences the antitumor immune response, efficacy, and safety of immune checkpoint inhibitors (ICIs). Antibiotics (ATBs), proton pump inhibitors (PPIs), and corticosteroids can alter the distribution of gut microbiota, resulting in dysbiosis, which can potentially reduce the efficacy of ICIs and may contribute to increased incidence of immune-related adverse effects (irAEs). Methods: We conducted a retrospective observational study to investigate the influence of concurrent medicines on patients receiving ICIs at the University of Vermont Cancer Center. We examined the medical records of people who received ICIs alone or in combination with chemotherapy or targeted therapy as a first-line therapy between January 2017 and June 2022. Patients who got ATBs, PPIs, and corticosteroids (>10 mg prednisone) one month before commencing ICIs and during the first six months of treatment were compared to those who did not. We looked at the relative risk for overall survival and the occurrence of irAEs in both cohorts. Results: We identified 266 patients, of which 99 (37%) have died. The mean age was 64 years, 55% were male, and 97% of the patients were White. Lung cancer was the most commonly identified malignancy at 36%, and 55% of the cancers were stage IV. The median ECOG was 1, and the median Charlson morbidity index was 6. Of the total cohort, 62% received antibiotics, 67% received steroids, 45% received PPIs, 31% received two of the three, and 27% received all three. The relative risk (RR) of death in the cohort which received antibiotics was 1.53 (p = 0.02), the cohort which received steroids was 1.73 (p = 0.006), and the cohort that received PPIs was 1.61 (p = 0.006). For the group that received two or all three medications, the RR was 2.18 (p = 0.003). Regarding irAEs, the group that received steroids had a RR of 2.13 (p = 0.07); however, most of these patients likely received steroids for an irAE. Antibiotics and PPIs were not associated with a higher risk of irAEs. One of the significant limitations of our study is the small sample size and the retrospective data collection. Data is also confounded because it includes patients who have received ICIs in combination with chemotherapy or other agents. Conclusions: Our study suggests that patients who received any of the gut microbiome-modifying medications before starting and within the early phase of ICIs treatments are at higher risk of mortality, likely owing to the poor efficacy of ICIs or possibly because these patients are sicker at baseline. However, we must be judicious with using such medications when patients undergo treatment with ICIs. Large prospective studies looking at this association are needed to understand the risk and potential outcomes. [Table: see text]
Cancer survival (SURVCANCER BRAZIL): Analysis of 132,621 cases from 19 hospital-based registries in southernmost Brazilian state comparing public and private insurance.
Authors: Giacomazzi Juliana , Maluf Fernando Cotait , Ferreira Sheila Schuch , Schneider Silvana , Vargas Alves Rafael Jose , Villarroel Rodrigo Ughini , Oppermann Christina Pimentel , Barros Sandra Helena Comassetto , Pozza Roberta , Bueno Marina Ractz , Zerwes Gustavo , Saueressig Silvia , Wilk Adriana Elisa , Seewald Rafael Armando , Costamilan Rita De Cassia , Weiss Bianca Tabajara , Capra Marcelo , Ziegelmann Patricia Klarmann
Published: June 2023

6632

Background: Brazilian data for cancer survival are scarce. Therefore, we aimed to describe the 5-year overall survival (OS) of individuals with public and private insurance from Rio Grande do Sul/RS (Brazil) diagnosed with the 17 most incident tumors in the country. Methods: Data from 19 of the 27 hospital-based cancer registries from RS were integrated with the Brazilian Information System data. Individuals with confirmed cancer diagnoses between 2005-2017 were included. Passive follow-up time was calculated as the difference between diagnosis and death (from any cause) or censure date. Survival was estimated by Kaplan-Meier method. Comparison between the survival of individuals assisted by public or private insurance was evaluated using hazard ratios (HR) estimated by multivariate Frailty and Cox regression models with adjustments for age, sex, and economic status. Results: 5-year OS was higher for patients with private health insurance for 13 of the 17 cancers studied. Conclusions: The survival trends among cancer patients assisted by public and private health insurance systems reveal vast differences that may be likely attributable to differences in access to early diagnosis and optimum treatment. We hope our results will help government officials understand that ongoing cancer survival surveillance is an indispensable source of information and a key policy tool for public health decisions. [Table: see text]
Real-world analysis of commercially insured and Medicare Advantage patients with advanced cancer and rates of molecular testing.
Authors: DaCosta Byfield Stacey , Bapat Bela , Becker Laura , Schroeder Brock , Spencer Scott , Chatzitheofilou Ismini , Hostin Damon , Fox John Leonard
Published: June 2023

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Background: Guideline-recommended molecular testing has become essential for biomarker-guided clinical decision making, particularly for patients with advanced (adv) disease. Several biomarkers have indications that are tumor type-agnostic (starting with MSI in 2017, NTRK in 2018, TMB in 2020, and RET and BRAF in 2022). Biomarker testing is covered by insurers, both Medicare (covers comprehensive genomic profiling [CGP] and non-CGP panels) and commercial (at least non-CGP). This study aimed to understand utilization of biomarker testing across tumor types. Methods: This retrospective analysis used de-identified administrative claims from Optum Labs Data Warehouse. Adult Commercial (COM) and Medicare Advantage (MA) enrollees diagnosed with any 1 of 6 adv cancer types from 1/2018 to 8/2021 were identified; the date of the first claim indicating adv cancer was the index date. Continuous enrollment for 12 months prior to (baseline), and ≥6 months post-index date, unless they died (follow-up) was required. Biomarker testing was captured using Current Procedural Terminology (CPT) codes indicating CGP (> 50 gene panels), non-CGP (at most 5-50 gene panels), or CPT code 81479 (unlisted molecular pathology procedure) during the study period. The primary analysis evaluates testing in the follow-up only, with secondary analyses evaluating testing including the baseline (to account for testing prior to the index date). Results: We identified 16,931 breast (BC), 16,838 non-small cell lung (NSCLC), 8,755 colorectal (CRC), 4,244 pancreatic (PC), 2,610 ovarian (OC), and 1,231 gastric (GC) adv cancer patients meeting study criteria. Overall biomarker testing rates in the follow-up period were: 37% NSCLC, 19% BC, 41% CRC, 35% PC, 51% OC, 35% GC. The Table shows testing rates by cancer, insurance type, and panel size during follow-up. Testing rates were lower among MA patients compared to COM patients. Even considering baseline and follow-up periods, overall biomarker testing rates were low, and lower among MA compared to COM : 48% NSCLC (53% COM, 47% MA), 27% BC (34% COM, 22% BC), 56% OC (61% COM, 53% MA),42% PC (53% COM, 38% MA), 47% CRC (56% COM, 42% MA), 41% GC (54% COM, 35% MA). Conclusions: Considering guideline recommendations, rates of biomarker testing across tumor types are far from optimal despite insurance coverage for testing. Identification of barriers to biomarker testing and interventions to overcome these are needed to improve adherence to biomarker testing guidelines. [Table: see text]
Prognosis and risk of suicide after cancer diagnosis.
Authors: Kinslow Connor J , Kumar Prashanth , Wall Melanie , Prigerson Holly Gwen , Olfson Mark , Kachnic Lisa A. , Horowitz David Paul , Yu James B. , Cheng Simon , Neugut Alfred I.
Published: June 2023

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Background: Suicide rates are elevated acutely after cancer diagnosis. We sought to create a unifying theory that explains variations in suicide risk across cancer sites, stages, and demographics. Based on the stress-diathesis model, we hypothesized that suicide risk correlates with cancer prognosis and that the impact of prognosis on suicide risk is greatest for populations with higher baseline risks of suicide. Methods: We identified all patients with newly diagnosed cancers from 2000-2019 in the Surveillance, Epidemiology, and End Results (SEER) 17 database, representing 27% of U.S. cancers diagnosed over the past 20 years. Multiple primary-standardized mortality ratios (SMR) were used to determine the relative risk of suicide within the first 6 months compared to the general U.S. population, adjusted for age, sex, race, and year of follow-up. We correlated suicide and 2-year overall survival rates for 20 cancer sites using a weighted linear regression model. Results: We identified 9,046 suicides among 6,811,940 persons diagnosed with cancer, 1,610 of which occurred within 6 months of diagnosis. There were 5.3 suicides per 10,000 person-years, compared with an expected rate of 1.7 (SMR 3.1 [95% CI 3.0-3.3]). Suicide risk correlated strongly with prognosis (increased risk of 9.5% per percent survival deficit at 2 years, R2 = 0.88, P < .0001). The impact of prognosis on suicide risk was greater for demographic groups with higher baseline risks of suicide. For men, the risk of suicide increased by 3 suicides per 10,0000 person-years (R2 = 0.84, P < .0001) versus 0.3 in women (R2 = 0.54, P < .0001). The impact of prognosis on suicide risk was also greater for persons age 60+ and for white (versus black) race. Conclusions: Poorer prognosis correlates with suicide risk in patients with cancer and has a greater effect on populations with higher baseline rates of suicide. Our model should provide a useful framework for triaging patients that need increased surveillance or urgent psychiatric referral.
A comparison of the Optum Clinicogenomics Solid Tumor Database and the SEER Population-Based Cancer Registry.
Authors: Woodward Alexa , Mohanty Pallavi , Yuan Tze-An , Liao Yun , Brenton Ashley
Published: June 2023

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Background: Real-world data (RWD) and real-world evidence (RWE) are increasingly utilized across a range of research and regulatory applications, including biomarker discovery, risk stratification, external control arms, and post-market surveillance. Two-thirds of FDA approvals in 2021 utilized genomic data and the growing interest in targeted therapies will likely continue this trend. While genomics or any one type of RWD alone yields an incomplete view of the patient journey, Optum’s clinicogenomic data links de-identified longitudinal clinical and claims data to next-generation sequencing (NGS) results. Ensuring the value of this data requires identifying and limiting biases and maximizing diversity. Methods: To evaluate the robustness and representativeness of Optum’s Clinicogenomic Solid Tumor Database, we compared demographic and clinical characteristics to the Surveillance, Epidemiology and End Results (SEER) database across 16 solid tumor types. Variables of interest included age at diagnosis, sex, self-identified race, year of diagnosis, and metastatic status. The Optum data was derived from clinical data that includes 156 million lives and claims data that covers 95 million lives. The solid tumor sub-cohort used for this analysis included 157,164 patients diagnosed between January 1, 2011, and December 31, 2021 with linked broad-panel NGS results. SEER Incidence Data included patients diagnosed between January 1, 2011, and December 31, 2018. Using the Optum data, we also report average continuous enrollment and sequential testing frequency across all solid tumor types. Results: The overall distributions of age at diagnosis, sex and race were similar across all cancer types, with a few exceptions. On average, SEER had a larger proportions of patients 80 years and older (15% vs 7.2%, all solid tumors) and of Asian race (7.1% vs 3.2%, all solid tumors). Cancer diagnoses in the Optum data increased year over year corresponding with the increasing availability and uptake of genetic testing in oncology, while the SEER data was equally distributed across all years. The average continuous enrollment for solid tumor patients was 8.1 years in the Optum data, and 13% of patients had sequential testing results from >1 time point. Conclusions: Given the increased reliance on RWD and RWE as part of the drug development and regulatory approval processes, ensuring the representativeness of clinicogenomic databases is paramount. This analysis of general patient characteristics across the Optum Clinicogenomics and SEER solid tumor databases found largely similar distributions of key variables. Observed differences between these two representative databases reflect the genetic testing landscape in oncology and provide the opportunity to investigate disparities related to accessing genetic services, corresponding targeted treatment options, and health outcomes.
Disparity in regional recruitment across global cancer trials: A meta-analysis.
Authors: Asghar Noureen , Naqvi Syed Arsalan Ahmed , Bibi Arifa , Ayaz Ahsan , Khakwani Kaneez Zahra Rubab , Prasad Aishwarya , Raza Umar , Thirumalareddy Joseph , Mirza Mohsin , Florez Narjust , Kamran Sophia C. , Riaz Irbaz Bin
Published: June 2023

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Background: Equitable regional enrollment in clinical trials is critical to addressing global inequities in health care outcomes. Therefore, we quantified disparities in regional recruitment in global cancer trials. Methods: Phase II/III clinical trials in prostate (PC), breast (BC), colorectal (CRC) and lung cancer (LC), and reporting regional recruitment were identified from Medline. Global regions were defined as North-(NA) and South- America (SA), Europe (EU), Africa (AF), Asia (AS), and Australia (AU). For multi-regional trials, enrollment incidence ratios (EIR) which compare region-wise trial enrollment against global estimates of region-wise specific cancer incidence obtained from Global Burden of Disease 2019 database. Trial-level EIRs were pooled using random-effects meta-analysis. A pooled EIR of < 1.0 indicates underrepresentation of a particular region in clinical trial enrollment compared to the actual burden of the specific cancer in that region. Statistical analyses were conducted in R v4.1.2. Results: Of the total 2125 trials identified, 1681 (79.1%) trials with 691,800 participants reported information regarding regional recruitment. Among those, only 1400 (65.9%) trials reported proportions of patients from pre-defined regions. A total of 1231 (57.9%) trials were single-regional recruiting patients from EU (589; 47.8%), NA (329; 26.7%), AS (295; 23.9%), AU (10; 0.8%), AF (4; 0.3%), and SA (4; 0.3%). There was significant underrepresentation of patients from AS (EIR: 0.47; 95% CI: 0.41-0.54) in cancer clinical trials. This was consistent across different cancers: PC (0.49; 0.35-0.71), BC (0.63; 0.43-0.94), CRC (0.63; 0.43-0.94), LC (0.39; 0.30-0.50). Similarly, there is a trend of under-representation of patients from AF (0.67; 0.43-1.04). Consistently, patients from were under-represented in PC (0.43; 0.24-0.77) and LC (0.26; 0.09-0.79) trials. Patients from NA (1.27; 1.08-1.51), EU (1.64; 1.57-1.72), and AU (5.41; 3.90-7.51) were significantly over-represented in multi-regional cancer clinical trials. The results are provided in table. Conclusions: There is suboptimal reporting of region-wise enrollment in cancer clinical trials. Representation of Africa and Asia in cancer clinical trials appears to be less than their expected share based on their burden of cancer incidence. [Table: see text]