tbuckley/cabot-search huggingface dataset:
Cost-effectiveness-analysis of different treatment modalities in bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NIMBC).
Authors: Constantin Rieger, Joerg Schluechtermann, Enno Storz, David A. Pfister, Axel Heidenreich
Journal: Journal of Clinical Oncology (2024)

556 Background: Elaborate treatment and repetitive surveillance makes bladder cancer to the most expensive cancer type over the lifetime of a patient with a peak in non-muscle invasive bladder cancer. Radical cystectomy (RC) as the Standard of Care in BCG unresponsive NMIBC is associated with a significant health-related quality-of-life burden (QALY). Gemcitabine/Docetaxel, Pembrolizumab or Hyperthermic Intravesical Chemotherapy (HIVEC) have recently been published as salvage treatment options trying to increase the rate of bladder preservation. Methods: We developed a Markov model from a payer´s perspective with the clinical data of single-arm studies for BCG unresponsive NMIBC (Gemcitabine/Docetaxel and Pembrolizumab) and our clinical data for patients receiving HIVEC (n=29) as intravesical salvage-chemotherapy. Costs were simulated with a non-commercial DRG-grouper, utilities were derived from comparable cost-effectiveness studies. We used a Monte-Carlo Simulation to identify the optimal treatment, comparing the incremental cost effectiveness ratios (ICER) in consideration of a willingness-to pay of 50.000 Euro/QALY. Results: Over a horizon of 10 years, Gemcitabine/Docetaxel, HIVEC and Pembrolizumab were associated with costs of 48.353 64.438 and 204.580 Euro, and QALY´s of 6.16, 6.48 and 6.00, resulting in an ICER of 26.482, 42.567 and 184.533 Euro in comparison to RC (costs: 21.871 Euro; QALY: 5.01). Monte-Carlo Simulation has identified HIVEC as the treatment of choice in the assumption of a WTP of &lt;50.000 Euro. QALY gains in Gemcitabine/Docetaxel and especially HIVEC were mainly driven by bladder preservation and the low rate of progression. Conclusions: Considering a WTP of &lt;50.000 Euro / QALY, Gemcitabine/Docetaxel and HIVEC are highly cost-effective therapy options in BCG unresponsive bladder cancer, while RC remains the cheapest option. At its current price, Pembrolizumab is only cost-effective with a price reduction of 70%.
Outcomes of patients (pts) with advanced renal cell carcinoma (aRCC) treated with cabozantinib (CABO) after lenvatinib plus pembrolizumab (LEN+PEM).
Authors: Jaime Ivan Haro-Silerio, Andrew Johns, Mohammad Jad Moussa, Mindy Wang, Emily Wang, Craig A. Kovitz, Matthew T Campbell, Eric Jonasch, Amishi Yogesh Shah, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2024)

433 Background: LEN+PEM is an approved first-line therapy for aRCC. In the CLEAR study, it produced a 71% objective response rate (ORR), an 18% complete response rate, and improved progression-free survival (PFS) and overall survival (OS) compared to sunitinib. CABO is approved as second and later line therapy for aRCC. We explored the efficacy of CABO in pts with aRCC after treatment with LEN+PEM. Methods: This is a retrospective study of pts with aRCC who received CABO after LEN+PEM at our institution from 12/2019 to 8/2023. Demographics and clinical data were abstracted from the EMR. A blinded radiologist assessed tumor response using RECIST v1.1. We measured PFS, time on therapy (TOT) and OS from start date of CABO. Results: 22 pts were analyzed (Table 1). Median follow up was 7.7 months (mo); 11 pts received LEN+PEM on the HOPE 111 trial (NCT02501096). Among all 22 pts, 11 (50%) had a partial response (PR), 5 (22.7%) had stable disease (SD), and 6 (27.3%) had progressive disease (PD) on LEN+PEM. Median TOT with LEN+PEM was 7.4 mo (range: 1.8-29). 20 pts (90.9%) discontinued LEN+PEM due to PD, 1 pt (4.5%) due to fatigue, and 1 pt (4.5%) due to elevated liver enzymes. 17 pts received CABO right after LEN+PEM; 3 pts received 1 line and 2 pts received 2 lines of therapy before CABO after LEN+PEM. Of 19 pts with evaluable radiographic response on CABO, 1 pt had a PR (ORR 5.3%, PFS 16.1 mo) and 3 pts had SD for ≥6 mo. Median TOT with CABO was 4.3 mo (range: 0.2-18.2); 13 pts (59.1%) took CABO for ≥4 mo, 7 pts (31.8%) took it for ≥6 mo, of which 3pts receivedpalliative radiation andcontinued CABO therapy beyond PD. Median PFS and median OS with CABO were 4.1 mo (range: 1.2-16.1) and 8.1 mo (range: 0.8-22.5), respectively. At time of analysis, 4 pts were still taking CABO (3 SD, 1 not yet evaluated); 15 pts discontinued CABO: 12 for PD, 1 for Grade 3 hand-foot skin reaction, 1 per pt request, and 1 for transition to hospice; 3 pts died during CABO therapy (bowel obstruction [1], COVID-19 [1], cardiac arrest [1]). Adverse events attributed to CABO were consistent with published reports. Conclusions: In this cohort of heavily pretreated pts who received CABO after LEN+PEM, CABO demonstrated a modest clinical benefit in a minority of pts, underscoring the need to develop effective novel therapies for aRCC. [Table: see text]
Clinical efficacy of lurbinectedin in metastatic neuroendocrine carcinomas of the genitourinary tract: Multi-institutional real-world experience.
Authors: Mohammad Jad Moussa, Syed Arsalan Ahmed Naqvi, Jaanki Khandelwal, Matthew T Campbell, Ana Aparicio, Bilal Ahmed Siddiqui, Alan Haruo Bryce, Parminder Singh, Omar Alhalabi
Journal: Journal of Clinical Oncology (2024)

601 Background: Neuroendocrine carcinomas (NEC) of the genitourinary (GU) tract, including small cell (SC) NEC and large cell (LC) NEC, are rare aggressive malignancies. Although highly sensitive to cisplatin-based chemotherapy, GU metastatic NEC (mNEC) have limited data to support next therapies. Lurbinectedin, a marine-derived alkylating drug and a selective inhibitor of oncogenic transcription and DNA repair pathways, is FDA-approved for small cell lung cancer (SCLC) after progression on frontline platinum-based therapy, with a disease control rate (DCR) of 68.6%. It is unknown whether DCR is similar in SCLC and GU mNEC. Methods: We report the first multi-institutional series (n=14) of lurbinectedin in GU mNEC. Imaging-based best overall responses (BOR) were noted as complete (CR), partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). DCR includes CR, PR, and SD. We use the Kaplan-Meier method for overall survival (OS) and progression-free survival (PFS) from lurbinectedin start date. We define duration of response (DoR) from response date to progression or last contact date for patients (pts) with CR or PR. Results: Most pts had a median age at metastasis of 70.5 years (ICR: 64-74.5) [Table]. Primary locations were bladder (7/14, 50%), prostate (5/14, 35.7%) and ureter (2/14, 12.3%). Histology at diagnosis mostly consisted of mixed or pure SCNEC, with one exception of LCNEC. Most pts had visceral disease, prior immunotherapy and at least 2 prior lines of therapy for mNEC before lurbinectedin (8/14, 57.1%). DCR was 6/14 (42.8%), including 5 bladder pts and 1 prostate pt. Among bladder pts, BOR included one CR (1/7, 14.3%) for the LCNEC case, 2 PR (2/7, 28.6%), 2 SD (2/7, 28.6%) and 2 PD (2/7, 28.6%). Most prostate and ureteral pts either progressed on lurbinectedin or were NE (Prostate: 1 PR, 2 PD, and 2 NE; Ureteral: 1 PD and 1 NE). For all 14 pts, median OS was 11.47 months (95% CI: 2.17-13.63) and median PFS was 2.8 mo (1.4-10.9). Median DoR was 7.38 mo (2.3-9.53) for 4 responding pts (CR or PR). Treatment was stopped due to progression (9/14, 64.3%), three adverse events [thrombocytopenia, electrolyte abnormalities, cerebrovascular accident] (3/14, 21.4%), and pt preference (1/14, 7.1%). Conclusions: Lurbinectedin offers encouraging responses (DCR: 5/7, 71.4%) close to those in SCLC, in previously treated bladder mNEC. One CR was noted for a bladder pt with LCNEC. Responses were less appreciated in prostate and ureteral mNEC due to NE responses and limited number. Larger cohorts are needed to confirm survival benefit and genetic analyses are warranted to identify characteristics of responders. [Table: see text]
EMBARK post hoc analysis of sexual activity (SA) patient-reported outcome (PRO) measures.
Authors: Stephen J. Freedland, John Mulhall, Martin Gleave, Ugo De Giorgi, Fred Saad, Antti Rannikko, Jasmina I. Ivanova, Anchen Nasr, Arlene Reisman, Arijit Ganguli, Pavol Kral, Neal D. Shore
Journal: Journal of Clinical Oncology (2024)

313 Background: In the phase 3 EMBARK trial (NCT02319837), enzalutamide (ENZ) + leuprolide (L) and ENZ monotherapy (mono) delayed metastasis-free survival (MFS) vs placebo (P) + L without impairing global health-related quality of life (HRQoL) in high-risk biochemically recurrent (BCR) nonmetastatic hormone-sensitive prostate cancer (nmHSPC) (PSA doubling time ≤9 months). A prespecified PRO analysis showed that SA (measured as a composite score using European Organization for Research and Treatment of Cancer QoL Questionnaire-Prostate 25 [QLQ-PR25]) was better preserved with ENZ mono vs P + L and no significant difference between ENZ + L vs P + L. A post hoc analysis at the HRQoL item level was conducted to understand the effect on SA in each comparison and enable shared decision-making between physicians and patients. Methods: Men with high-risk BCR nmHSPC were randomized (1:1:1) to ENZ + L (double blind), ENZ mono (open label), and P + L (double blind). HRQoL was assessed at baseline and every 12 weeks until metastasis/death. This post hoc analysis assessed effects on time to confirmed (two consecutive visits) deterioration (TTCD) using predefined thresholds of one category decline from baseline in sexual interest, activity, satisfaction, erectile function, and feeling like a man using QLQ-PR25 item 50; QLQ-PR25 item 51; FACT-P item GS7; FACT-P item BL5; and FACT-P item P5 measures, respectively (Table). Intent-to-treat principle was applied. Results: At baseline, 327–332 men per arm completed the PRO surveys; overall completion rates were ≥85%, except for GS7 (≤36% due to voluntary response). ENZ mono vs P + L : TTCD in items 50 (interest) and 51 (activity), GS7 (satisfaction), and BL5 (erectile function) was delayed with ENZ mono. ENZ + L vs P + L: no significant differences in TTCD were observed, except a shorter TTCD by a median 0.06 months in BL5 (erectile function) with ENZ + L (Table). Conclusions: This post hoc item-level analysis of the EMBARK trial confirmed that SA was better preserved with ENZ mono vs P + L in terms of interest, activity, satisfaction, and maintaining erection. Further, the SA PROs were similar between ENZ + L and P + L, implying there is no further SA burden when adding ENZ to androgen-deprivation therapy. Clinical trial information: NCT02319837 . [Table: see text]
Impact of a rash management guide on incidence and severity of rash with apalutamide: Experience from the Apa-RP study in high-risk localized prostate cancer.
Authors: Neal D. Shore, Jason Hafron, Daniel Saltzstein, Amitabha Bhaumik, Pankaj Aggarwal, Rushikesh Potdar, Jennifer Phillips, Tracy McGowan
Journal: Journal of Clinical Oncology (2024)

316 Background: Apa-RP is a multicenter, open-label, single-arm Phase 2 study of adjuvant treatment with apalutamide and androgen deprivation therapy (ADT) in treatment-naïve patients with high-risk localized prostate cancer who underwent radical prostatectomy (NCT04523207). A rash management guide was implemented to improve dermatologic adverse events (AEs) that included proactive patient education on appropriate skin care and monitoring for rash, and frequent outreach through patient phone calls. We present rash-related safety data from Apa-RP compared with data from 2 Phase 3 apalutamide registrational studies. Methods: 108 patients were treated with apalutamide 240 mg once daily with ADT for 12 28-day cycles. Rash occurrence was monitored and skin-related AEs were defined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading scale. These factors were collated and compared with data from the North American population from SPARTAN (non-metastatic castration-resistant prostate cancer; NCT01946204) and TITAN (metastatic castration-sensitive prostate cancer; NCT02489318). Results: Of 108 patients in Apa-RP, 21.3% developed rash vs 28.3% in SPARTAN and 33.3% in TITAN. Information on rash severity, median time to onset of first rash, the proportion of patients with rash resolution, median time to resolution and the treatment administered for rash are provided in the Table. Conclusions: The Apa-RP rash management protocol demonstrates a proactive and patient-empowered approach to monitoring and managing patients on apalutamide who develop skin rash. With increased vigilance from the care team and appropriate patient education, it may be possible to reduce the incidence, severity and median time to resolution of skin rash. Clinical trial information: NCT04523207 . [Table: see text]
Final results of a phase I trial of HERV-E TCR transduced T cells for the treatment of HLA-A*11 patients with metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Rosa Nadal, Stefan Barisic, Gina M. Scurti, Elena Cherkasova, Long Chen, Kristen Wood, Steven L. Highfill, Brian Wells, Georg Aue, Reem Shalabi, Thomas E. Hughes, Xin Tian, Yifei Xu, Ashkan A. Malayeri, Robert N. Reger, Michael I. Nishimura, Richard W. Childs
Journal: Journal of Clinical Oncology (2024)

435 Background: Human endogenous retrovirus type E (HERV-E) is specifically expressed in ccRCC providing a safe target for T cell-based therapies. We investigated T cells transduced with a TCR targeting HERV-E (HERV-E T cells) for the treatment of mccRCC. Methods: This first-in-human study assessed the safety &amp; efficacy of escalating doses of HERV-E T cells and manufacturing/clinical endpoints correlative analysis. HLA-A*11+ mccRCC patients (pts) were treated with a conditioning regimen, infusion of HERV-E T cells &amp; IL-2. (NCT03354390). Results: Nineteen of185 pts tested were found to express HLA-A*11. 17 HLA-A*11 + pts enrolled on the study: 3 pts on each DL1-3 &amp; 6 pts on DL4. 2 pts did not receive HERV-E T cells given disease progression during manufacturing period. Median age was 57 years. 86% received ≥ 3 prior systemic treatment (range 1-8). The manufacturing failure rate after first apheresis was 12% (n=2); both met target dose after second apheresis and repeat in vitro expansion. All HERV-E T cell products met release criteria for infusion including INF-γ production in response to HERV-E/HLA-A11-expressing tumor cells. Median HERV-E vector copy number (VCN) was 1.9. No dose-limiting toxicities (DLT), off-target toxicities or treatment-related deaths occurred. Pt#17 is on DLT monitoring period. 7 pts completed the planned 14 doses of IL-2 and all received at least 8 doses. Reasons for IL-2 discontinuation: hemodynamic (57%), cardiovascular (28%), pulmonary (28%), renal (14%) criteria &amp; pts decision (14%). The best response was partial response in 7% &amp; stable disease at least 8 weeks in 29% pts. HERV-E mRNA expression was detected in 5 primary &amp; 9 metastatic specimens. HERV-E T cells were measurable in circulation post-dosing, with peak concentrations in the peripheral blood mononuclear compartment on day(D)+7. [DL1: 0.3 %, DL2: 1.2%, DL3: 0.5%, DL4: 12.3%]. Median HERV-E T cell VCN showed no correlation with HERV-E T cells peak concentration on D+4 &amp; D+7. Conclusions: Proof of concept that HERV-T cells can induce tumor regression without evidence of causing off-target toxicities has been established by this trial. Infused HERV-E T cells were detectable transiently in vivo and induce effector cytokine production. Our initial results support the further development of HERV-E-directed therapies that focus on methods to improve in vivo persistence of TCR engineered T-cells and to target HERV-E antigens expressed on more commonly expressed HLA alleles.[Table: see text]
Improving health education through a patient-clinician partnered intervention in the patient with genitourinary cancer.
Authors: Jessica Parker
Journal: Journal of Clinical Oncology (2024)

TPS525 Background: Health literacy is associated with health equity, acts as a cornerstone in optimizing patient care and is associated with improved quality of life. The objective of this project is to improve health literacy in patients with genitourinary cancer through a patient-clinician partnered education intervention. Synthesis of Literature Utilization of a targeted education program delivered in-person using voice instruction demonstrated the greatest significant effect on health-related quality of life; the additional of illustration and text further improved this metric. Optimal health related quality of life is associated with greater comprehension of disease and adherence to treatment plan, heightened self-efficacy, and improvement in patient-provider communication. Methods: The intervention is a patient-clinician partnered written form used in conjunction with verbal instruction. The patient documents reasons for the visit and primary concerns to be addressed prior to the provider encounter during the visit. The Action Plan then records the treatment plan and next steps discussed during the visit. A Confidence Ruler acts as a visual representation of patient confidence in the plan of care, acting as a prompt to the provider to ensure adequate information transfer at conclusion of the visit. The patient then retains the written form highlighting the care discussion for reference and recall as needed. Evaluation A five-point Likert test will measure change pre/post intervention; data will be analyzed in a cohort looking at improvement in overall mean. The HRQOL-14 and the CHLT-6 modified will be used to assess baseline health related quality of life and health literacy respectively followed by cohort analysis of the means to determine efficacy outcomes. The primary outcome is to improve health literacy in all patients within a genitourinary oncology clinic population using is a written tool in concurrence with verbal instruction with secondary focus on improving health-related quality of life in the same population. Recommendation Health literacy must be assessed each visit to optimize patient care outcomes and quality of life. Targeted health education must be patient specific and titrated to individual health literacy needs.
A retrospective cohort study to monitor real-world safety in patients with locally advanced or metastatic urothelial carcinoma (LA/mUC) treated with sacituzumab govitecan (SG) in the United States.
Authors: Mamta Parikh, Freda Boateng, Susan Eng, Mitch Sierecki, Fangfei Chen, Jane Michelle Brockman, Youssef Ghazi, Leslie Ng
Journal: Journal of Clinical Oncology (2024)

608 Background: Patients with LA/mUC experience poor outcomes, with few treatment options historically available. In April 2021, SG (a TROP-2-directed antibody drug conjugate) received accelerated approval for patients with LA/mUC who progressed after platinum-based chemotherapy and immune checkpoint inhibitor therapy, based on the pivotal TROPHY U-01 trial (NCT03547973). We sought to evaluate SG safety in patients with LA/mUC treated in routine clinical practice in this study. Methods: A retrospective cohort of patients aged ≥ 18 years with LA/mUC treated with SG in the United States was evaluated using data from the nationwide Flatiron Health electronic health record–derived de-identified database (from Jan 2011 to Oct 2022). Outcomes included patient characteristics, treatment patterns, adverse events (AEs) of interest incidence, and granulocyte-colony stimulating factor (G-CSF) use. Descriptive statistics were used for data analysis. Results: This study included 86SG-treated patients (male, 70%; median age, 71 [range: 25-85] years; 27% with ECOG ≥ 2; 84% treated in community settings). Most patients (71%) received enfortumab vedotin (EV) in the direct prior line. The majority of patients received SG as monotherapy (94%), with most patients overall (99%) receiving SG as second-line (2L) or later. The most common AEs of interest (any grade, overall) were diarrhea (35%), neutropenia (40%) and nausea/vomiting (21%) (Table). Of the 86 patients, 14 (16%) patients were hospitalized, 8 (9%) discontinued SG treatment likely due to AEs/toxicity, and 3 (3%) died during or within 7 days after the line of treatment. During SG treatment, 52% of patients used G-CSF (primary prophylaxis 24%; secondary prophylaxis 19%; therapeutic use 28%). Only 1 (4.5%) patient who had primary G-CSF prophylaxis developed grade ≥ 3 neutropenia. Conclusions: This study is the largest analysis of SG use in a real-world population with LA/mUC to date; it provides insights into the safety of SG in this setting. Compared with prior data, this real-world population was older, with poorer functionality, and the majority received EV in the direct prior line. Observed AEs were consistent with the known safety profile of SG and indicate that this sequencing is feasible. [Table: see text]
Economic burden of radical cystectomy and trimodal therapy for bladder cancer in the United States: Real-world study.
Authors: Stephen B. Williams, Halit O. Yapici, Puneet K. Singhal, Ian Weimer, Farah Pathan, Kunal Lodaya, Haojie Li
Journal: Journal of Clinical Oncology (2024)

555 Background: Bladder cancer (BC) is exponentially deadly once it invades muscle, with the highest per patient treatment costs among cancers. Radical cystectomy (RC) and trimodal therapy (TMT) are recommended treatment options for muscle-invasive BC. This study describes patient/treatment characteristics and short- and long-term costs/healthcare utilization (HCU) associated with RC and TMT. Methods: Patients with BC undergoing RC or TMT were identified using Optum claims data (October 2015-April 2023). Incident cases were captured, and individuals diagnosed with a prior BC, secondary bladder neoplasm, and non-bladder malignancies were excluded. Costs and HCU (e.g., inpatient, outpatient, emergency, pharmacy) were evaluated up to 5 years of follow-up. Results: Median [IQR] ages of the RC (N=839) and TMT (N=484) cohorts were 71 [66-76] and 75 [69-81] years, and NCI comorbidity index was 0.50±0.43 and 0.52±0.45, respectively. Median follow-up durations were 30 [19,47] and 32 [20,48] months for RC and TMT patients, respectively. Median cost and HCU per patient in the RC cohort were $70,671 [$55,878-$106,812] with 26 [16-39] visits in 3 months, $103,579 [$71,12-$158,489] with 56 [39-86] visits in 12 months and increased to $211,671 [$138,597-$346,389] with 163 [119-218] visits in 60 months. For TMT, median cost and HCU per patient were $34,612 [$16,705-$64,263] with 19 [12-33] visits in 3 months, $116,259 [$65,300-$188,622] with 72 [46-94] visits in 12 months, and increased to $274,462 [$186,337-$421,534] with 186 [144-238] visits in 60 months (N=72). Outpatient care was the highest cost contributor for both cohorts across all time periods, except the first 3 months for RC, where inpatient care was predominant. Approximately 25% (N= 211) of patients received neoadjuvant chemotherapy before RC. For patients receiving TMT, median radiotherapy fractions delivered was 36 [18-43], and 8.1% underwent salvage RC. Conclusions: The burden of RC or TMT-treated BC patients remains high, suggesting key targets for cost containment to optimize value-based care. However, our costs are lower compared to previous literature, possibly due to 3 rd party payer (i.e., closed networks), treatment advancements, and patient selection. Future research should evaluate the cost and HCU implications of guideline-recommended treatments i.e., neoadjuvant chemotherapy followed by RC vs. TMT with advised chemotherapy type/duration for both. [Table: see text]