bluuebunny/crossref_metadata_2025 huggingface dataset:
CeNtuRIOn: Rucaparib (R) with nivolumab (N) and ipilimumab (I) in patients (pts) with relapsed ovarian cancer (ROC)—Results of an initial safety cohort.
Authors: Hall Marcia , Allan Karen , Michael Agnieszka , Clamp Andrew R. , Glasspool Rosalind , Nicum Shibani , Lord Rosemary , Banerjee Susana N. , Roche Joshua , Stobo Jamie , Gourley Charlie ,   CeNtuRIoN Trial Group
Published: June 2022

5577

Background: There is an urgent need to improve outcomes for ROC pts; progression free (PFS)/overall survival (OS) are 4-9 months (mo), 12-20mo respectively. ̃50% ROC pts harbour homologous repair deficiencies (HRD), identified by BRCA mutations (m) & Loss of Heterozygosity (LoH). R, a PARP inhibitor (PARPi) has demonstrated efficacy when used as maintenance after chemotherapy (CT), and is superior to CT if used as treatment for ROC BRCAm pts. However repeating PARPi, even in highly selected BRCAm/HRD pts has limited benefit (1.5-2.5mo extra PFS). Single agent immunotherapy (PD-1/PD-L1/CTLA4 antibodies (Ab)) in ROC pts has been disappointing. Response rate to combined PD-1/CTLA4 Ab in ROC pts is 31.3%. In vitro evidence suggests that combinations of PD-1/CTLA4 Ab /PARPi may be more effective. CeNtuRIOn aims to explore the activity/toxicity of repeat PARPi (R) versus R+I (CTLA4 Ab) versus R+I+N (PD-1 Ab). Here we report safety data from the run-in cohort of 15 ROC pts treated with the triplet combination, RNI. Methods: Eligible pts had received ≥1 and <3 lines CT, were > 3 to <12 months from last platinum CT. Only 1 pt could experience a dose limiting toxicity (DLT) over initial 6 weeks of treatment. Pts received N 240mg q14 days, I 1mg/kg q42 days intravenously for up to 12mo and R orally, 600mg bd continuously. All bar 1 of 7 pts (recruited 06/19–12/19) received N+I to meet DLT evaluability, but 5 of remaining 6 received < 43% R during safety period. 6 further pts were recruited (08/20-06/21), with ≥60% starting dose R in first 6 weeks now required for evaluability. Review of toxicity/tolerability prompted reduction of R starting dose to 400mg bd and ipilimumab limited to 4 cycles for the last 4 pts. Results: Of all 15 recruits, median age was 64. Adverse events (AE)s are detailed in Table. 7 pts were evaluable for safety assessment: n = 4 started on 600mg bd and n = 3 on 400mg bd R. Median R dose intensity in these 7 was 82.5%. There was 1 DLT: G3 nephritis on day 18. 1 pt died of E. Coli sepsis related to colitis. Outcome data will be presented. Conclusions:R (400mg bd)+N+I (4 cycles only) will be taken forward to phase II. Pts will be randomised 1:1:2 to single agent R, R+I or RNI. Pts recruited to R alone are eligible for 2nd randomisation (1:1) to add I or N+I at progression. Clinical trial information: ISRCTN10490346. [Table: see text]
Trends in frontline PARP inhibitor maintenance in advanced epithelial ovarian cancer across the United States.
Authors: Huelsmann Erica , Deng Mengying , Handorf Elizabeth A. , Chu Christina , Jain Angela
Published: June 2022

5581

Background: Advanced epithelial ovarian cancer (AEOC) is the fifth commonest cancer mortality among women in the United States. Despite 80% initial treatment response, most recur within two years and succumb from disease. Prolonging disease free interval with maintenance therapy is of interest. Options include Poly-(ADP) ribose polymerase inhibitors (PARPi’s) and Bevacizumab, an anti-angiogenesis agent; eligibility criteria are based on clinical trials. Here we examine national approach to front line maintenance therapy following treatment in AEOC with focus on PARPi use. Methods: Protocol for data collection was IRB approved and institutional IRB approved. A retrospective, observational cohort study using Flatiron Health electronic health record (EHR)-derived, de-identified database patients diagnosed with AEOC between March 2017-June 2020, following FDA approval of PARPi use in AEOC. Demographics were summarized using descriptive statistics by use of maintenance treatment, and associations were tested using ANOVA and Chi-squared tests. Trends in use and type of maintenance therapy were summarized by year. Time trends assessed by Cochran–Armitage tests. Results: 1196 patients met inclusion criteria: Age>18, Stage III-IV, 90-day gap rule, systemic therapy after diagnosis. Majority were >65, White, Stage III with ECOG 0 at diagnosis. Only 31.6% of patients received maintenance after frontline therapy. Single agent PARPi was most used (12.9%), and Olaparib was most used PARPi (57%). Use of maintenance therapy significantly differed by ECOG value at diagnosis (p=.005), region of practice (p=.003), use of surgery (p=<.001) and extent of debulking (p=.002). Maintenance therapy was used more often when ECOG low at diagnosis, optimal debulking achieved and with treatment in the Southern US. Maintenance therapy significantly increased by year (p=<0.001); highest in 2020 (46.9%). Type of maintenance therapy had a significantly different trend by year with PARPi becoming more common (p=<.001). Conclusions: Despite known high rates of response to maintenance PARPi and increased use over time, less than 50% of patients with AEOC receive this regimen. Reasons for low adoption of maintenance PARPi in this population with poor prognosis deserves further investigation. Olaparib, approved for single use in BRCA mutation carriers in the front-line maintenance setting was used more often than Niraparib, approved for all comers. [Table: see text]
Bevacizumab combined with platinum-based chemotherapy in patients with primary or relapsed ovarian cancer: Meta-analysis and literature review.
Authors: Abodunrin Faith , Tauseef Abubakar , Silberstein Peter T.
Published: June 2022

5582

Background: Epithelial ovarian cancer has the highest mortality rates among all gynecological malignancies and is the fifth leading cause of cancer-related deaths in females. Previously, the treatment of ovarian cancers included cytoreductive surgery in combination with platinum-based chemotherapy. While this treatment regimen initially resulted in a good response, most of the patients subsequently relapsed. Given the role of Vascular Endothelial Growth factor (VEGF) and angiogenesis in the progression of ovarian cancer, VEGF inhibitors such as Bevacizumab were considered in the treatment of advanced or relapsed ovarian cancer patients. We conducted a meta-analysis to compare the efficacy of Bevacizumab with platinum-based chemotherapy to platinum-based chemotherapy. Methods: A thorough systematic literature review identified five eligible studies reporting the efficacy of bevacizumab with platinum-based chemotherapy in the treatment of advanced or recurrent Ovarian cancer as compared to control group receiving platinum-based chemotherapy alone. These studies were randomized Phase III clinical trials, one of which was recently published in 2021. Summary estimates of the clinical endpoints were calculated with risk ratio (RR) and 95% confidence intervals using the random-effects model. Heterogeneity between studies was examined with COCHRAN’S Q based 12 statistics. The primary endpoint was progression free survival at 12 months while secondary endpoints were overall survival and certain adverse effects. Results: Our pooled analysis from the five studies included 4,648 patients. 2,641 were in the Bevacizumab and platinum-based treatment group while 2007 patients in sole-platinum based chemotherapy group. There was a statistically significant difference in primary outcome of progression free survival at 12 months was noted (RR = 1.56 (95% CI: 1.09 to 2.24; p = 0.020). 33,4% of patients in the treatment group as compared to 22.9% observed in the control group attained PFS at 12 months. The secondary outcome of overall survival at 12 months was seen in 76.7% patients in treatment group as compared to 73.02% observed in control group. This was no statistically significant difference in this case (RR = 1.04 (95% CI: 0.96 to 1.12; p = 0.34). Adverse effects including hypertension, proteinuria, arterial and venous thromboembolism, posterior reversible leukoencephalopathy syndrome occurred more frequently in the treatment group. Conclusions: Results from our meta-analysis support the superiority of Bevacizumab with platinum-based chemotherapy over platinum-based chemotherapy with regards to PFS. However, the OS benefit remains questionable.
Survival outcomes for dostarlimab and real-world (RW) treatment (tx) paradigms in post-platinum patients (pts) with advanced/recurrent (A/R) endometrial cancer (EC): The GARNET trial versus an external control arm from the Flatiron Health database.
Authors: Coleman Robert L. , Shen Qin , Goulden Scott , Mathews Cara Amanda , Hunger Matthias , Pahwa Ankit , Schade Rene
Published: June 2022

5593

Background: There are limited treatment options for pts with A/R EC progressing on or after platinum-based chemotherapy (PBCT) and their prognosis is poor. This study compared the efficacy of the anti-programmed death (PD)-1 antibody dostarlimab evaluated in the single-arm, Phase I GARNET trial with current RW tx. Overall survival (OS) of pts with A/R mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) EC receiving dostarlimab in Cohort A1 of the GARNET trial was compared with an equivalent RW cohort receiving non-anti-PD-(ligand [L])1 tx. Methods: The dostarlimab arm was the GARNET (Cohort A1) dMMR/MSI-H EC safety population. For the external control arm, a RW cohort was constructed using the Flatiron Health database and aligning eligibility criteria with those for GARNET, including pts with A/R EC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1, who had received ≤2 lines of chemotherapy (≥1 line PBCT) and no anti-PD-(L)1 therapy. GARNET pts who received anti-PD-(L)1 therapy following dostarlimab (n=5/129) were excluded. Inverse probability of tx weighting (IPTW) was performed based on propensity scores constructed from key prognostic factors identified by literature review and clinical experts. With IPTW, Kaplan–Meier curves were created, OS rates estimated, and adjusted hazard ratios (HR) estimated by a Cox regression model. MMR/MSI status, only partially available in Flatiron and considered not significantly prognostic for OS as per a recent meta-analyses, was not included in the IPTW. Results: Baseline characteristics for GARNET (N=124) and RW (N=185) after IPTW are shown in the Table. Dostarlimab was associated with a 44% lower risk of death compared with RW tx (OS HR [95% confidence interval {CI}] 0.56 [0.385–0.812]; p=0.002) (see Tablefor median OS). Survival rates (95% CI) were higher for dostarlimab than RW tx at 12 months (mos) (72% [57%–82%] vs 51% [43%–59%]), 18 mos (57% [41%–70%] vs 40% [32%–48%]), and 24 mos (53% [37%–67%] vs 34% [26%–42%]). Conclusions: These results indicate that pts with A/R EC receiving dostarlimab in the GARNET trial had significantly lower risk of death than those receiving current non-anti-PD-(L)1 tx in the RW.[Table: see text]
Biomarker associations of immune checkpoint inhibitor versus chemotherapy effectiveness in first-line metastatic endometrial carcinomas: A real-world study.
Authors: Santin Alessandro , Graf Ryon , Shah Kunal J. , Kelly Andrew David , Danziger Natalie , Lin Douglas I. , Oxnard Geoffrey R. , Elvin Julia Andrea
Published: June 2022

5596

Background: Limited evidence exists comparing outcomes of single-agent anti-PD1 immune checkpoint inhibitors (ICPI) vs. chemotherapy in the 1st line among metastatic endometrial carcinoma (mEC) patients. dMMR, MSI status, and Tumor Mutational Burden (TMB) have been characterized as predictive biomarkers of ICPI response in many solid tumors, including mEC. We sought to evaluate ICPI vs. chemotherapy effectiveness in 1st line mEC, stratified by TMB ≥ 10 mut/MB and MSI as assessed by next-generation sequencing. Methods: Following a prespecified analysis plan, this study used the nationwide (̃280 US cancer clinics) de-identified, EHR-derived, Flatiron Health-Foundation Medicine mEC clinico-genomic database (FH-FMI CGDB), with tissue CGP between 1/2011 - 6/2021. Cohort inclusion criteria: recurrent mEC patients with stage I-III at original diagnosis, 1st line ICPI or platinum chemotherapy treatment with TMB and MSI assessments available. Adjusted hazard ratios (aHR) from multivariable Cox proportional hazard models were utilized for time to next treatment (TTNT) and overall survival (OS) comparisons between 1L chemotherapy and 1L ICPI from start of 1L treatment stratified by TMB (≥ 10 vs. < 10) and adjusted for ECOG, BMI, and stage at diagnosis. Results: Among the 1st line cohort, patients received either Chemotherapy (n = 139, 87%) or first-line ICPI (n = 20, 13%). While the overlap between the TMB ≥ 10 (n = 46) population and MSI-H (n = 39) populations was high, with 38/46 (83%) of TMB ≥ 10 classified as MSI-H and 38/39 (97%) of MSI-H with a TMB ≥ 10, there were also 8 (17%) TMB ≥ 10 patients who were MSS. TMB ≥ 10 was associated with more favorable TTNT (aHR: 0.11 [0.03 - 0.44]) and OS (aHR: 0.1 [0.01 - 0.82]) on single-agent ICPIs vs. chemotherapy; however, TMB < 10 patients exhibited no observed differences in TTNT (aHR: 1.66 [0.79 - 3.48]) or OS (aHR: 1.79 [0.66 - 4.8]) between treatments. MSI-H pts were associated with more favorable TTNT (aHR: 0.1 [0.02 - 0.39]) and OS (aHR: 0.1 [0.01 - 0.86]) on single-agent ICPIs over chemotherapy; however, MSS pts did not observe differences in TTNT (aHR: 1.5 [0.65 - 3.5]) or OS (aHR: 2.14 [0.63 - 7.26]) between ICPI vs. chemotherapy. Conclusions: Recurrent 1st line mEC patients with TMB ≥ 10 and/or MSI-H exhibit more favorable outcomes on single-agent ICPI than standard chemotherapy in real-world settings. These findings warrant prospective randomized validation. Future studies should assess the utility of a combined biomarker approach across TMB and MSI status to identify the broadest group of patients who might benefit from ICPI.
Disparity between Ki67 measurements and tumor gene expression tests in patients with hormone-sensitive early breast cancer from the OPTIMA preliminary trial.
Authors: Stein Robert C. , Marshall Andrea , Bayani Jane , Makris Andreas , MacPherson Iain R. , Hughes-Davies Luke , Sobol Monika , Piper Tammy , Dotchin Georgina , Higgins Helen , Shaaban Abeer , Pinder Sarah E. , Dunn Janet , Bartlett John ,   OPTIMA Trial Management Group
Published: June 2022

567

Background: Tumor gene expression tests are increasingly used in breast cancer management. The Ki67 biomarker has been proposed as an inexpensive alternative for making chemotherapy decisions, has demonstrated utility for determination of endocrine therapy responsiveness and is included in the FDA license for adjuvant abemaciclib. We have compared Ki67 measurements with tumor gene expression test results for patients included in the OPTIMA prelim trial. Methods: We compared Ki67 %staining with the results of Oncotype DX, Prosigna and MammaPrint performed by the test vendor. Ki67 was determined in a single laboratory on triplicate tissue micro-arrays using quantitative image analysis including a 10% manual quality control check. We used kappa statistics to measure agreement between tests, divided into groups using the pre-defined test score boundaries for high vs. not high risk. Results: Data were available for 259 patients. Using ≥20% staining to define a high Ki67 score, kappa values (95% CI) for agreement with Prosigna were: 0.39 (0.28-0.49); Oncotype DX: 0.27 (0.18-0.36); and MammaPrint: 0.38 (0.27-0.49). Kappa values <0.2 are conventionally interpreted as showing slight agreement and 0.21-0.4 as fair agreement. A detailed breakdown of the comparisons of Ki67 with Prosigna and Oncotype DX is tabulated. Conclusions: Agreement between Ki67 and tumor gene expression tests is limited. Therefore, Ki67 values cannot accurately be used to reflect any of the molecular scores assessed here, all of which are well validated prognostic biomarkers. The use of Ki67 to determine suitability for adjuvant chemotherapy requires validation before it can replace the existing tests. Tumor gene expression tests may prove superior to Ki67 for the identification of patients likely to benefit from adjuvant abemaciclib. OPTIMA prelim is registered as ISRCTN42400492 and funded by the UK NIHR Health Technology Assessment Programme, award number 10/34/01. Clinical trial information: ISRCTN42400492. [Table: see text]
Distribution of breast cancer molecular subtypes within receptor classifications: Lessons from the I-SPY2 Trial and FLEX Registry.
Authors: Cha Jaeyoon , Warner Paige , Hiatt Robert , Gomez Scarlett Lin , van 't Veer Laura , Stover-Fiscalini Allison , Borowsky Alexander , Symmans W. Fraser Fraser , Wolf Denise M. , Yau Christina , Yee Douglas , DeMichele Angela , Berry Donald A. , Esserman Laura , Audeh William M. , Modh Shraddha ,   I-SPY2 Consortium
Published: June 2022

592

Background: Expression-based molecular subtypes of breast cancer (BC) predict tumor behavior and therapeutic response. Subtype distributions by age and sociodemographics can inform strategies for BC screening, treatment, and prognosis. The conventional approach, adopted by NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, uses HR and HER2 to label: “triple negative” (HR-HER2-), “HER2-enriched” (HR-HER2+), “luminal A” (HR+HER2-), and “luminal B” (HR+HER2+). However, immunohistochemical (IHC)-based receptor labels may not reflect clinically and epidemiologically relevant molecular subtypes that share the same nomenclature, e.g., luminal B. Methods: We compared IHC labels by HR/HER2 to molecular subtypes by MammaPrint (MP) and BluePrint (BP) for patients in the phase II neoadjuvant I-SPY2 TRIAL for high-risk, stage II-III BC (NCT01042379, n = 981) and in the multicenter, prospective FLEX Registry for stage I-III BC (NCT03053193, n = 5,679). Results: IHC labels were discordant with MP/BP in 52% of I-SPY2 and 43% of FLEX cases (Table 1). HR-HER2- had the highest concordance with basal-type (99% in I-SPY2, 88% in FLEX). HR+ labels had the least agreement with MP/BP: HR+HER2- tumors were molecularly luminal B and basal in 71% and 29% of I-SPY2 and 40% and 4% of FLEX cases, respectively. HR+HER2+ tumors were molecularly luminal A and HER2-type in 10% and 60% of I-SPY2 and 15% and 36% of FLEX cases, respectively. Of molecularly luminal B cases, only 14% in I-SPY2 and 7% in FLEX were HR+HER2+. Conclusions: IHC markers collected by population-based registries (SEER) enable BC surveillance. However, IHC labels cannot be used as surrogates for molecular subtypes by MP/BP, especially for luminal B tumors. Given the unmet need to improve management of luminal B BC, we anticipate the growing importance of molecular subtyping to inform treatment and epidemiological research. We propose that the BC research community work with SEER to update its IHC labels to avoid overlap with molecular subtype nomenclature and incorporate such modern classifications when available. [Table: see text]
Racial and ethnic disparities in adherence and reported symptoms during routine collection of patient-reported outcomes (PROs).
Authors: Takvorian Samuel U , Wu Yaxin , Gabriel Peter Edward , Iocolano Michelle , Bekelman Justin E. , Shulman Lawrence N. , Parikh Ravi Bharat
Published: June 2022

6510

Background: Routine collection of PROs for patients with cancer is an evidence-based practice and critical component of high-quality cancer care, but real-world adherence and reporting patterns are poorly understood. We examined differences in PRO adherence and reported symptoms by race and ethnicity. Methods: We conducted a retrospective cross-sectional study using de-identified electronic health record data from a National Cancer Institute Comprehensive Cancer Center. Participants included adults seen in follow-up at one of two medical oncology practices (1 academic, 1 community) from June 2019 to February 2020, during which two validated PRO instruments (NCI PRO-CTCAE and PROMIS Global v1.2) were routinely administered electronically via portal or tablet at return visits. Adherence was defined for each participant as the proportion of visits in which a PRO questionnaire was completed within 30 days. Using ordinary least squares regression, we modeled patient adherence as a function of race/ethnicity and adjusted for age, sex, insurance, median area income, ECOG performance status, cancer type, cancer stage, visit site, and number of visits during the study. Among study participants completing at least one PRO questionnaire, we modeled reported symptoms from the first questionnaire using a similar approach. Results: From June 2019 to February 2020, there were 29,726 patients (mean [SD] age 60.8 [15.1] years; 18,045 [60.7%] female) seen across 111,262 medical oncology visits. Of these patients, 19,971 (67.2%) completed at least one PRO questionnaire. Adjusted mean PRO adherence and reported symptoms varied by race/ethnicity, with Black and Hispanic patients reporting significantly higher symptom burden than White patients (Table). Conclusions: In this large cohort reflecting real-world PRO collection patterns, Black and Hispanic patients were less likely than White patients to complete PRO questionnaires, but more likely to report more severe symptoms. There is urgent need to ensure equitable PRO access and implementation and to address greater reported symptom burden among minority patients. [Table: see text]
Parental informed consent comprehension in childhood cancer clinical trials: Associations with social determinants of health.
Authors: Aristizabal Paula , Nataraj Shilpa , Perdomo Bianca , Martinez Elena , Nodora Jesse , Thornburg Courtney D
Published: June 2022

6512

Background: Adequate informed consent (IC) comprehension is an ethical right prior to participation in clinical trials. Research investigating IC comprehension and associations with social determinants of health (SDoH) is lacking. We assessed whether SDoH and related contextual factors were associated with parental IC comprehension in therapeutic childhood cancer clinical trials. Methods: We prospectively enrolled parents of children with newly-diagnosed cancer. Univariable and multivariable regression were used to assess whether objective IC comprehension and related domains ( Purpose/Procedures/Randomization, Risks/Benefits, Alternatives, and Voluntariness) were associated with SDoH (ethnicity, marital status, language, education attainment, employment, insurance, socio-economic status, health literacy [HL]) and contextual factors (cancer type, voluntariness, satisfaction with IC). Results: Of 223 parents included, 112 (50%) were Hispanic and 38% of Hispanics were monolingual Spanish-speaking. In adjusted multivariable analyses, limited HL was significantly associated with lower overall IC comprehension (β = -7.22; 95% CI, -10.9 to -3.59; P < 0.001) and lower comprehension of Purpose/Procedures/Randomization (β = -7.53; 95% CI, -11.3 to -3.73; P < 0.001), Risks/Benefits (β = -8.14; 95% CI, -15.5 to -0.772; P = 0.031), and Alternatives (β = -17.0; 95% CI, -30.5 to -3.57; P = 0.013). Preferred Spanish language of written/verbal medical information was significantly associated with lower comprehension of Purpose/Procedures/Randomization (β = -8.50; 95% CI, -15.1 to -1.89; P = 0.012) and Voluntariness (β = -20.1; 95% CI, -34.9 to -5.33; P = 0.008). Lower satisfaction with informed consent (β = 0.988; 95% CI, 0.460 to 1.52; P < 0.001) and single marital status (β = -4.42; 95% CI, -7.81 to -1.02; P = 0.011) were significantly associated with lower IC comprehension. Conclusions: Among parents of children with newly diagnosed cancer who provided consent for their child’s participation in a therapeutic clinical trial, limited HL was consistently associated with lower IC comprehension in all domains analyzed, except for Voluntariness. Spanish language preference for medical information was associated with lower comprehension of two domains; and lower satisfaction was associated with lower overall IC comprehension. These findings suggests that parents with limited HL, limited English-proficiency, and lower satisfaction may not fully comprehend the IC and thereby not truly make informed decisions. Our findings highlight the potential role of language-concordant interventions tailored to the participant’s HL level in order to ultimately improve IC comprehension and contribute to a reduction of disparities in clinical trial participation and promote equitable translation of discoveries and treatments to underserved groups.
Analysis of patient (pt) withdrawal of consent using 11,993 pts from 58 alliance for clinical trials in oncology trials.
Authors: Mandrekar Sumithra J. , Hillman Shauna L , Strand Carrie , Zahrieh David , George Suzanne , Jatoi Aminah
Published: June 2022

6513

Background: Pt recruitment receives well-deserved attention, but pt retention is also important for trial interpretability and generalizability. We report on trends and predictive factors for withdrawal of pt consent, defined as pt cessation from trial participation for reasons not mandated in the protocol. Methods: Alliance phase II/III trials that enrolled pts during 2013 – 2019 were included. All pts had ≥2 years (yrs) of follow-up. Primary outcome was withdrawn consent (yes; no) within 2 yrs of enrollment. Pt factors included year of enrollment, age, race, ethnicity, and gender. Trial factors included randomization, use of placebo, and use of radiation. Univariable (Uni) and full multivariable (MV) logistic regression models (including all factors from Uni setting) with a Bonferroni p-value correction (p <.004 considered significant) were used. Results: Median age was 62 yrs, with 67% female, 82% White, 9% Black or African American, and 7% Hispanic. 52% of trials were phase II, 5% II/III and 43% III. Common (> 10%) trial categories included 22% experimental therapeutics or rare tumors, 12% gastrointestinal, 12% genitourinary, 12% neuro-oncology and 10% symptom intervention. 78% of trials were randomized, 22% placebo-controlled and 14% used radiation. 1060 (9%) pts withdrew consent within 2 yr of enrollment (range,5.7% -9.8%) during 2013-2019. In Uni models, all trial and pt factors significantly predicted pt withdrawal except age, race, and gender (See table). In MV models, pts of Hispanic origin, and >75 yrs were more likely to withdraw. Trials using radiation had less likelihood of pt withdrawal. Placebo-controlled randomized trials had higher likelihood of withdrawal. Conclusions: Both trial and pt factors contribute to higher rates of pt withdrawal from clinical trials. Understanding these factors will enable investigators to focus on pt education and optimization of trial design to improve pt retention and the overall clinical trial plan. Support: U10CA180821, U10CA180882 [Table: see text]
Neighborhood socioeconomic disadvantage, tobacco use, and cessation indicators among adults with cancer in the United States: Results from 10 ECOG-ACRIN trials.
Authors: Walter Angela Wangari , Lee Ju-Whei , Gareen Ilana F. , Kircher Sheetal Mehta , Herman Benjamin A. , Streck Joanna M. , Kumar Shaji , Mayer Ingrid A. , Saba Nabil F. , Neal Joel W. , Atkins Michael B. , Hodi F. Stephen , Kyriakopoulos Christos , Tempany Clare , Shanafelt Tait D. , Wagner Lynne I. , Land Stephanie R. , Ostroff Jamie S. , Park Elyse R.
Published: June 2022

6514

Background: Tobacco use is a modifiable risk factor for adverse outcomes among patients diagnosed with cancer. Despite ASCO’s recommendation for assessment and treatment of tobacco use, integration into cancer care is suboptimal. Socioeconomic contexts influence access and utilization of tobacco treatment, but little is known about the relationship between neighborhood socioeconomic disadvantage (NSD) and tobacco assessment, assistance, and cessation among cancer patients enrolled in clinical trials. Methods: The NCI Cancer Patient Tobacco Use Questionnaire (C-TUQ) was centrally administered to participants enrolled in 10 ECOG ACRIN clinical trials (9 therapeutic, 1 imaging). We examined associations of NSD with patient-reported rates of receiving brief tobacco cessation support (i.e., Ask, Assist (counseling)) and cessation (past 30d quit attempts and duration). NSD was measured using the national Area Deprivation Index (ADI) based on participant’s zip code. Associations between ADI (low, intermediate, and high) and tobacco variables were evaluated using logistic regression and ANOVA. Results: 740 patients, completing the C-TUQ between June 2017-October 2021, can be classified as 402 (54%) never smokers, 81 (11%) current smokers, and 257 (35%) former smokers. Patients were 70% male; 94% white; 3% Hispanic; mean age 58.8 (SD 9.0). Cancer diagnoses were 36% leukemia; 19% lymphoma, 18% prostate, 11% breast; 9% melanoma, 7% myeloma, and 0.5% head and neck. Patients were categorized into high (33%), intermediate (34%) and low (33%) disadvantaged neighborhoods. Patients in high (vs. low) disadvantaged neighborhoods were more likely to report being asked about smoking (OR = 3.90; 95% CI (confidence interval), 1.61 to 9.46; p = 0.0062) but less likely to report receiving counseling to help quit smoking (OR = 0.20; 95% CI, 0.06 to 0.73; p = 0.0234). Patients from high disadvantaged neighborhoods had the shortest quit duration, followed by patients from intermediate and low disadvantaged neighborhoods (mean = 145.78, 187.66, and 210.98 months, respectively, p = 0.0372). Conclusions: Greater socioeconomic neighborhood disadvantage was associated with increased assessment of tobacco use but decreased tobacco treatment referral, and the shortest quit duration. More research is needed to promote increased referral to tobacco treatment for individuals with cancer from disadvantaged neighborhoods to promote and sustain cessation.
Cancer risk factors and cancer in transgender versus cisgender people: Real-world data from a tertiary health care institution.
Authors: Alpert Ash B. , Sayegh Sabrina Jamileh , Strawderman Myla S. , Cunliffe Scott , Cupertino Ana Paula , Cerulli Catherine , Griggs Jennifer J.
Published: June 2022

6538

Background: Data are sparse regarding the prevalence of cancer and cancer risk factors among transgender people. Transgender people experience structural stigma and extreme rates of violence that may contribute to cancer through multiple mechanisms. The purpose of this study was to assess cancer risk factors and cancer in transgender people in a single institutional electronic health record (EHR) and compare the rates to those among cisgender, or non-transgender, people. Methods: Using a combination of structured gender identity data, diagnosis codes, and keyword searches, we identified a cohort of transgender people seen at our institution, a large tertiary care center. We next identified a cohort of cisgender people matched by age, year of first encounter in our EHR, and years of follow-up. Among these cohorts, we searched for cancer, premalignant lesions, human immunodeficiency virus (HIV), human papilloma virus (HPV), and hepatitis and assessed body mass index (BMI) and smoking status through structured EHR fields. Lastly, we compared the prevalence of cancer, premalignant lesions, and cancer risk factors between the two cohorts using chi-square tests. If expected cell sizes were <5, exact tests were used. Results: We identified cohorts of 923 transgender and 1846 cisgender people matched by age, follow-up time, and year of the first encounter. Rates of smoking (42 versus 34%, p < 0.0001), BMI ≥ 40 (21% versus 13%, p < 0.0001), and HIV (3 versus 0%, p < 0.0001) were significantly higher among transgender compared with cisgender people. Rates of premalignant lesions and cancer did not significantly differ between cohorts. Conclusions: In this large sample of patients seen at our institution, rates of several cancer risk factors were higher for transgender than cisgender people. No differences were demonstrated in prevalence of premalignant lesions and cancer between groups. These data require confirmation in larger national datasets. Interventions that decrease structural oppression and provide support for tobacco cessation, decreased transmission of HIV, and access to high-quality food and exercise are also called for. [Table: see text]
Disparities in delayed diagnosis, access to treatment, and treatment delays among Hispanic men with metastatic prostate cancer.
Authors: Swami Nishwant , Dee Edward Christopher , Mahal Brandon A
Published: June 2022

6550

Background: Reporting racial/ethnic disparities in aggregate for Hispanics could obscure differences between subgroups given heterogeneity in social determinants of health. We sought to identify differences in delayed diagnosis, treatment status, and time to treatment among Hispanic subpopulations with metastatic prostate cancer. Methods: 2004-2017 data from the National Cancer Database (NCDB) was used to identify patients with prostate adenocarcinoma; patients were disaggregated by racial subgroup and Hispanic country-of-origin. Ordinal logistic regression defined adjusted odds ratios (aORs) with 95% CI of 1) presenting with Stage IV cancer, 2) receiving treatment, and 3) receiving delayed treatment (defined as treatment after 90 days). Sensitivity analysis was conducted for delayed treatment after 180 days. Results: Among 1,305,785 patients, Hispanic men had greater odds of presenting with stage IV prostate cancer compared with non-Hispanic White (NHW) men (aOR = 1.54 95% CI 1.50-1.58, p < 0.001). All Hispanic racial subgroups were more likely to present with stage IV cancer with highest odds observed in Hispanic Black men (aOR 1.68 95% CI 1.46-1.93, p < 0.001). Disparities were also observed in all country of origin subgroups, particularly for men of Mexican heritage (aOR 1.99 95% CI 1.86-2.12, p < 0.001). Among men with metastatic disease, Hispanic men were less likely to receive treatment than NHW men (aOR 0.60 95% CI 0.53-0.67, p < 0.001). Hispanic White patients were less likely to receive treatment compared with NHW men (Hispanic White aOR 0.58 95% CI 0.52-0.66, p < 0.001). Upon disaggregation by country of origin, disparities persisted, particularly for men of Dominican heritage (aOR 0.52 95%CI 0.28-0.98 p = 0.044). Hispanic men were more likely to experience treatment delays when compared to NHW men (aOR 1.38 95%CI 1.26-1.52 p < 0.001). All Hispanic racial subgroups experienced greater treatment delays, particularly Hispanic Black men (aOR 1.83 95%CI 1.22-2.75 p = 0.002). Men of Central or South American heritage had the greatest odds of treatment delays (aOR 1.48 95%CI 1.07-2.04 p = 0.018). Sensitivity analysis indicated consistent findings among Hispanic patients overall, Hispanic White patients, and patients of Mexican and Puerto Rican heritage. Conclusions: We found notable differences in stage IV cancer at presentation, treatment for metastatic disease, and delays in treatment when outcomes were stratified by racial subgroup and Hispanic country of origin. Future studies in Hispanic populations with disaggregated data are needed to characterize outcomes, study mediators of the observed variations, and develop targeted interventions.
Medicare expenditures for discarded oncology therapies.
Authors: Scheckel Caleb , Desai Aakash , Jensen Chelsee , Orme Jacob , Pritchett Joshua , Mahipal Amit , Khera Nandita , Go Ronald S.
Published: June 2022

6552

Background: Significant amounts of expensive oncology drugs are discarded resulting in waste and financial consequences for patients. Beginning in 2023, the Infrastructure Investment and Jobs Act (IIJA) will require drug manufacturers to refund Medicare for any single-use drugs where greater than 10% of the drug is wasted. We explored potential IIJA-associated savings through assessment of patterns in spending for discarded oncology agents between 2017-2020. Methods: We utilized the Medicare Part B Discarded Drug Units database from 2017-2020. Using J codes, we extracted spending and reimbursement data for discarded medications for antineoplastic and classical hematology therapies. The primary outcome was identification of therapies with high percentage of waste and the economic impact of retroactive application of the IIJA for discarded therapies. Results: Medicare Part B utilization data was extracted for a median 77 (64-152) oncologic therapies per year with median reimbursement for discarded treatments of $590 M ($566-616). From 2017-2020, bortezomib, romiplostim, and nab-paclitaxel were consistently among the top 5 therapies by value of wasted product. Pembrolizumab waste by value declined significantly after 2017 following transition to fixed dosing. In 2020, the top 5 therapies by value of wasted product were bortezomib, nab-paclitaxel, trastuzumab, romiplostim, and cabazitaxel with a value of $278 M. In 2020, the agents with the highest percentage of wasted product were bortezomib (27%), cabazitaxel (28%), decitabine (23%), topotecan (23%), and azacitidine (22%) with a collective discarded value of $160 M. Notably, these agents have weight-based dosing and single-use vials. Based upon the average number of drug claims per recipient and volume of product discarded, eliminating drug waste would allow an additional 6564 patients to receive treatment with discarded bortezomib. The number of additionally treated patients for the other top 5 agents: cabazitaxel (1216), decitabine (1509), topotecan (291), and azacitidine (2682). Retroactive application of IIJA policy would have impacted a median 20 (12-26) oncology agents resulting in median annual cost savings of $153 M (142-157) and the median annual spending on wasted oncology therapies would decline to $440 M (410-466). Conclusions: The IIJA would have yielded a median annual savings of $153 M in Medicare spending if applied retroactively. Given a 10% waste cutoff, a limited number of agents would be targeted by this legislation. In our study, we observe that drugs associated with weight-based dosing and single-use drug vials account for most drug waste. Strategies to minimize discarded units (through storage of unused product, approval of multi-dose vial formulations, or fixed-dose therapies) could yield substantial savings while enabling health equity in collaboration with communities with difficult access to these drugs.
Updated health-related quality of life of patients with TRK-fusion cancer treated with larotrectinib in clinical trials.
Authors: Kummar Shivaani , Shen Lin , van Tilburg Cornelis Martinus , Tan Daniel S.W. , Doz Francois , McDermott Raymond S. , Zwaan C. Michel , Keating Karen N. , Chirila Costel , Norenberg Ricarda , Fellous Marc Mardoche , Brega Nicoletta , Xu Rui-hua , Laetsch Theodore Willis , Drilon Alexander E. , Hong David S.
Published: June 2022

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Background: NTRK gene fusions have been identified as oncogenic drivers in patients (pts) with TRK fusion cancer across multiple solid tumors. Larotrectinib, a highly selective, CNS-active TRK inhibitor has shown high response rates, durable disease control, and a favorable safety profile in pts with TRK fusion cancer and is approved in over 40 countries. Larotrectinib has demonstrated rapid health-related quality of life (HRQOL) improvement in a group of 57 adult and pediatric pts (Kummar et al, Curr Prob Canc 2021). Here, we report updated HRQOL results for larger group of pts treated with larotrectinib. Methods: HRQOL data were collected in two ongoing trials (NCT02576431, NCT02637687) of larotrectinib in pts with TRK-fusion cancer using the EORTC QLQ-C30, EQ-5D-5L questionnaires and were analyzed descriptively and longitudinally. Scores from the EORTC QLQ-C30 Global Health Status (GHS), EQ-5D-5L VAS range from 0 to 100, with higher scores indicating better QOL. We also calculated the proportion of pts with either below normal or normal and above normal HRQOL scores against values in the literature for the US general population. Results: By July 2021, 113 adults with TRK-fusion cancer had received larotrectinib and completed the baseline (BL) and ≥ 1 post-BL questionnaire. The majority of pts had clinically meaningful HRQOL improvements during treatment (Table). For EORTC QLQ-C30 GHS, most adults maintained or improved scores from BL at or above the normal population level category. HRQOL improvements (change from BL > 0) occurred after ̃2 months of treatment in 75% of adults. Median duration of pts with sustained improvement in EORTC QLQ-C30 GHS, and EQ-5D-5L VASs was 12.5 months (range, 1.8-34.1), and 12.9 months (range, 1.8-34.0), respectively. HRQOL results were consistent across multiple data cuts. Conclusions: Patients with TRK-fusion cancer treated with larotrectinib continued to have rapid, clinically meaningful, and sustained improvements in HRQOL. Clinical trial information: NCT02576431, NCT02122913, NCT02637687.
Lisocabtagene maraleucel (liso-cel) as second-line (2L) treatment (tx) for R/R large B-cell lymphoma (LBCL) in patients (pt) not intended for hematopoietic stem cell transplantation (HSCT): Patient-reported outcomes (PRO) from the phase 2 PILOT study.
Authors: Gordon Leo I. , Hoda Daanish , Shi Ling , Guo Shien , Liu Fei Fei , Braverman Julia , Dubowy Ronald L. , Peng Lily , Sehgal Alison
Published: June 2022

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Background: PILOT (NCT03483103) evaluated liso-cel, an autologous, CD19-directed, CAR T cell product, as 2L tx in pts with R/R LBCL not intended for HSCT. We analyzed changes in health-related quality of life (QOL) with respect to functioning and symptoms in PILOT. Methods: Adults with R/R LBCL after first-line tx were eligible. Pts were deemed not candidates for high-dose chemotherapy and HSCT by their physician and met ≥ 1 frailty criteria: age ≥ 70 yr, ECOG PS = 2, DLCO ≤ 60%, LVEF < 50%, CrCl < 60 mL/min, or ALT/AST > 2 × ULN. Pts completed EORTC QLQ-C30, FACT-LymS, and EQ-5D-5L (health utility index [HUI] and VAS) at screening (baseline [BL]), pre-tx (within 7 days before lymphodepletion), preinfusion on day of liso-cel infusion (Day 1), post-tx on Days 29, 60, 90, 180, 270, 365, 545, and 730/end of study, or at PD. The PRO-evaluable set included all pts with BL and ≥ 1 post-BL assessments. Linear mixed-effects models for repeated measures assessed the least squares (LS) mean change from BL for visits with ≥ 10 pts. Meaningful change from BL was calculated using responder definitions (in points): 10 for EORTC QLQ-C30, 3 for FACT-LymS, 0.08 for EQ-5D-5L HUI, and 7 for EQ-VAS. Results: Among the PRO-evaluable set, completion rates were high (≥ 80%) across most visits for all measures. For EORTC QLQ-C30, mean BL fatigue was meaningfully worse than in a general noncancer population (difference of > 10 points). Overall LS mean changes through Day 545 showed significant improvements in EORTC QLQ-C30 fatigue and pain, FACT-LymS, and EQ-VAS (Table). Improvement for lymphoma symptoms was also clinically meaningful. Fatigue improvement was clinically meaningful with a more sensitive minimal important difference of 4 (Cocks et al, 2012). Significant worsening was not observed for any outcome. In individual patient-level analysis, 70% of pts demonstrated meaningful improvement in FACT-LymS at month 6. Conclusions: Liso-cel meaningfully improved fatigue and FACT-LymS scores without negatively impacting other QOL measures. These data support the clinical evidence of liso-cel as a potential new 2L tx in pts with R/R LBCL not intended for HSCT. Clinical trial information: NCT03483103. [Table: see text]
Polypharmacy and premature aromatase inhibitor (AI) discontinuation in older women with breast cancer.
Authors: Joyce Elizabeth , Kidwell Kelley M. , Stearns Vered , Hayes Daniel F. , Storniolo Anna Maria , Henry Norah Lynn
Published: June 2022

6568

Background: Treatment with AI therapy for at least five years is recommended to reduce risk of cancer recurrence in postmenopausal women with hormone-positive breast cancer, but up to 50% prematurely discontinue their AI. Prior studies have demonstrated higher rates of nonadherence in older patients. Higher rates of comorbidities are also present in older patients, many of which require treatment with prescription medications. However, in prior studies, the impact of polypharmacy on AI persistence in older women has been variable. We evaluated the relationship between use of prescription and over-the-counter (OTC) medications and AI discontinuation in older women in a randomized controlled trial of AI therapy. Methods: In the Exemestane and Letrozole Pharmacogenetics (ELPh) trial, postmenopausal women with stage 0-III hormone-positive breast cancer were randomized to receive exemestane or letrozole and followed for two years. Prescription medication and OTC supplement usage was prospectively collected. Only enrolled participants at least 65 years of age were included in this analysis. Univariate and multivariable Cox proportional hazards models evaluated the association between baseline prescription medications, OTC medications, initial assigned AI medication, and time to discontinuation of initial AI. Results: 131 women at least 65 years old with baseline medication and OTC supplement information were identified. The average age was 70.4 (SD 5). 58 participants (44%) were randomized to exemestane and 73 (56%) to letrozole. 21% had previously received tamoxifen and 18% received taxane-based chemotherapy. The average number of prescription medications at AI initiation was 4.95, and 127 patients reported taking at least one. The average number of OTC medications was 3.23, and 107 patients reported taking at least one. There was no difference in number of prescription medications or OTC medications by study arm. As previously reported, exemestane was associated with premature discontinuation (HR 1.92 [95%CI 1.06-3.50], p = 0.032). Controlling for AI, the risk of discontinuation decreased by 12% for every additional prescription medication (HR 0.88 [95%CI 0.78-0.99], p = 0.038). OTC medication use was not significantly associated with AI duration. Conclusions: Increased prescription medication usage at AI initiation was associated with decreased risk of premature discontinuation of AI. Further research is needed to evaluate this interaction and identify characteristics that impact AI persistence in older women with breast cancer. Clinical trial information: NCT00228956.