tbuckley/cabot-search huggingface dataset:
Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory Pediatric B-Cell Acute Lymphoblastic Leukemia
Authors: John K. Lin, Benjamin J. Lerman, James I. Barnes, Brian C. Boursiquot, Yuan Jin Tan, Alex Q.L. Robinson, Kara L. Davis, Douglas K. Owens, Jeremy D. Goldhaber-Fiebert
Journal: Journal of Clinical Oncology (2018)

Purpose The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel was recently approved to treat relapsed or refractory pediatric acute lymphoblastic leukemia. With a one-time infusion cost of $475,000, tisagenlecleucel is currently the most expensive oncologic therapy. We aimed to determine whether tisagenlecleucel is cost effective compared with currently available treatments. Methods Markov modeling was used to evaluate tisagenlecleucel in pediatric relapsed or refractory acute lymphoblastic leukemia from a US health payer perspective over a lifetime horizon. The model was informed by recent multicenter, single-arm clinical trials. Tisagenlecleucel (under a range of plausible long-term effectiveness) was compared with blinatumomab, clofarabine combination therapy (clofarabine, etoposide, and cyclophosphamide), and clofarabine monotherapy. Scenario and probabilistic sensitivity analyses were used to explore uncertainty. Main outcomes were life-years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (3% discount rate). Results With an assumption of a 40% 5-year relapse-free survival rate, tisagenlecleucel increased life expectancies by 12.1 years and cost $61,000/QALY gained. However, at a 20% 5-year relapse-free survival rate, life-expectancies were more modest (3.8 years) and expensive ($151,000/QALY gained). At a 0% 5-year relapse-free survival rate and with use as a bridge to transplant, tisagenlecleucel increased life expectancies by 5.7 years and cost $184,000/QALY gained. Reduction of the price of tisagenlecleucel to $200,000 or $350,000 would allow it to meet a $100,000/QALY or $150,000/QALY willingness-to-pay threshold in all scenarios. Conclusion The long-term effectiveness of tisagenlecleucel is a critical but uncertain determinant of its cost effectiveness. At its current price, tisagenlecleucel represents reasonable value if it can keep a substantial fraction of patients in remission without transplantation; however, if all patients ultimately require a transplantation to remain in remission, it will not be cost effective at generally accepted thresholds. Price reductions would favorably influence cost effectiveness even if long-term clinical outcomes are modest.
Cumulative burden of morbidity (CBM) among testicular cancer survivors (TCS) in the Platinum study.
Authors: Sarah L. Kerns, Chunkit Fung, AnnaLynn Williams, Mohammad Issam Abu Zaid, Howard D. Sesso, Patrick Monahan, Shirin Ardeshir-Rouhani-Fard, Darren R. Feldman, Robert James Hamilton, David J. Vaughn, Clair Beard, Deepak M. Sahasrabudhe, Sophie D. Fossa, Lawrence H. Einhorn, Lois B. Travis
Journal: Journal of Clinical Oncology (2016)

10089 Background: Few studies systematically evaluated CBM in adult-onset cancer survivors, accounting for number and severity of adverse health outcomes. TCS provide a unique opportunity to do so, given their young age at diagnosis, relatively homogeneous cisplatin-based chemotherapy (CHEM) and high cure rates. We comprehensively evaluated CBM among TCS enrolled in an ongoing multicenter investigation. Methods: Eligible TCS (aged < 50 y at diagnosis, given first line CHEM) completed comprehensive health questionnaires and prescription drug usage. Responses were mapped and graded using the NCI CTCAEv4.03, resulting in > 35 graded health outcomes. A CBM score was calculated based on number and severity of each outcome, following Geenen et al.(JAMA 2007). Ordinal logistic regression examined the relationship between clinical factors and CBM and between CBM and self-reported health. Results: Among 751 TCS (median age at evaluation 38 y, range 19-68 y; time since CHEM 4.6 y, range 1-30 y), the most common health outcomes were obesity (42% grade 2, 29% grade 3, 4% grade 4), sensory neuropathy (28% grade 1, 18% grade 2, 17% grade 3), motor neuropathy (27% grade 1, 11 % grade 2, 6% grade 3), tinnitus (31% grade 1, 7% grade 2, 7% grade 3), and hearing loss (27% grade 1, 15% grade 2, 1.3% grade 3, 0.1% grade 4). Low, medium, high, and severe CBM scores were observed in 8%, 69%, 20%, and 0.5% of TCS, respectively. Only 3% of TCS had no adverse health outcomes, and nearly 90% had a CBM score of at least medium. Older age at evaluation was significantly associated with worse CBM score (OR 1.04; 95% CI 1.03, 1.06; p < 0.001). When including health outcomes considered to be related to cisplatin exposure, each 100 mg/m2 increase in cisplatin dose was associated with significantly worse CBM (OR per 100 mg/m2 1.30; 95% CI 1.14, 1.67; p = 0.007) after adjusting for age at evaluation and bleomycin use. Increasing CBM score was significantly associated with worse self-reported health (OR 2.56, 95% CI 2.03, 3.21; p < 0.001). Conclusions: CBM after CHEM appears relatively early and is strongly correlated with worse self-reported health, indicating TCS perceive this as impacting negatively on their health. Survivorship care plans for TCS should take into account the CBM.
BP-C1 in the treatment of primary inoperable pancreatic cancer.
Authors: Stig Einride Larsen, Tarek M.M. Ibrahim
Journal: Journal of Clinical Oncology (2017)

e15708 Background: The aim was to estimate the efficacy and tolerability of intramuscular administration of a new benzene-poly-carboxylic acids complex with cis-diammineplatium (II) (BP-C1) in treatment of primary inoperable pancreatic cancer patients Methods: The study was an open, single center, non-randomized trial with security sequential design. The study sample consists of 12 patients with a mean age 61.8 years, BMI 23.9 and disease duration 1.8 months. The patients received daily intramuscular injection of 0.035 mg/kg bw BP-C1 for 32 days. NCI Bethesda (CTC-NCI) and EORTC QOL-C30 were recorded at screening, after every 16 days of treatment and 28 days follow-up. CT-scans performed at screening, after 32-days BP-C1 treatment and follow-up. The RECIST criteria used for tumor evaluation and the sum diameters of the three largest lesions measured. Patient classified as responding to treatment if Stable Disease (SD) or better was obtained. Results: The number of target lesions was unchanged from screening to Day 32. The sum lesion diameters declined from 47.3 mm at screening to 46.3 after 32 days of BP-C1. During follow-up, the sum diameters declined significantly (p = 0.03) to 14.0 mm. After 32 days of treatment, three patients classifies as Progressive Disease (PD) and nine as SD: A responds rate of 75% (95% CI: 42.8 – 94.5%). After 28 days follow-up, five patients classifies as PD, three as SD and four as PR: A responds rate of 58.3% (95% CI: 27.7 – 84.8%). “Discomfort last week” and “Physical activity problem” declined significantly (p &lt; 0.01) and “Health and life quality” increases significantly (p &lt; 0.01) from screening to Day 16 and Day 32. Sum CTC score increase non-significantly from 9.8 at screening to 12.3 and 13.4 after 16 and 32 days of treatment, respectively. During follow-up, the score decreased to 8.8. Thirty AE recorded. Ten classified as “Unrelated”, seven as “Possibly”, 12 as “Probably” and one as “Definite” related to the trial treatment. Of the 20 AE, which might be related to the treatment, 12 classifie as “Mild”, six as “Moderate”, one as “Severe “and one as “Life-threatening”. Conclusions: BP-C1 reduce the cancer growth, improve quality-of-life and well tolerated with only few mild to moderate AE.
Qualitative study of cancer patients’ advance care planning (ACP) values.
Authors: Rajiv Agarwal, Angelo E. Volandes, Danielle R. Romano, Margaux Genoff, Eileen Mary O'Reilly, William Breitbart, Andrew S. Epstein
Journal: Journal of Clinical Oncology (2018)

e22151 Background: Person-Centered Oncologic Care and Choices (P-COCC) is a validated ACP paradigm of a values-focused patient (pt) interview augmented by an informational care goals video. In a randomized trial (Epstein et al ASCO 2017), P-COCC was acceptable but more distressing than usual care or video alone. To ask why, we qualitatively analyzed P-COCC interviews. Methods: Thematic content analysis was performed on transcripts of audio-recorded values interviews of advanced gastrointestinal cancer pts. For reliability and analytic rigor, 2 reviewers met in weekly iterative consensus rounds. Primary analysis phase consisted of identification of key domains to guide coding, line-by-line coding with ATLAS.ti software to generate a codebook, and quality assurance. Secondary analysis phase consisted of independent review and categorization of codes, followed by 18 successive consensus meetings to identify distinct themes. Results: From the P-COCC narratives of 48 pts, 109 codes were generated and categorized into 15 values code families. Thematic consensus analysis resulted in 8 distinct themes across domains of medical treatment preferences, communication needs, and psycho-social supports: 1) most pts favored limited or comfort care; 2) life-prolonging care was associated with a negative emotional response (e.g. fear of artificial existence, poor life quality, value-discordant care); 3) the video was generally well-accepted and informative, but pts questioned its appropriateness in relation to their state of illness and readiness to engage in ACP; 4) pts trusted the oncology team; 5) concerns (e.g. fear, uncertainty) about illness and prognosis drove a desire for open communication and being understood; 6) relationships with loved ones provided meaning to pts’ lives; 7) religion and spirituality enhanced inner strength and support; and 8) pts valued maintaining an identity, keeping agency, and living life outside of cancer. Conclusions: In advanced cancer, addressing core values can increase distress, which seems brought on by sensitive but pertinent ACP topics on end-of-life medical care. Future work should address how psycho-social supports can be leveraged during the ACP process to optimally inform and guide pts. Clinical trial information: NCT01912131.
Patritumab (P) or placebo (PBO) plus cetuximab (C) and platinum-based therapy in squamous cell carcinoma of the head and neck (SCCHN): a phase 2 study.
Authors: Kevin J. Harrington, Martin David Forster, Magnus Dillon, Lorna Grove, Sola Adeleke, Shuquan Chen, Jane S. Diamond, Henrik Hannus, Kandance Cooper, Jonathan Greenberg
Journal: Journal of Clinical Oncology (2016)

TPS6104 Background: P is a fully human monoclonal antibody against human epidermal growth factor receptor 3. P blocks activation by the ligand, heregulin (HRG), inducing receptor internalization. Evidence is growing that HRG presence determines disease progression and survival; in a phase 2 study in non–small-cell lung cancer, P + erlotinib increased progression-free survival (PFS) in high HRG mRNA expression (HRG-high) patients. A phase 1b study in SCCHN demonstrated safety, tolerability and tumor response of P + C + cisplatin or carboplatin and informed the P phase 2 dose. January 2016 (N = 15) response rate = 47%; best responses = 3 complete response (CR), 4 partial response (PR) and 8 stable disease (SD). This phase 2 study (NCT02633800) evaluates first-line P + C + platinum (P arm) vs. PBO + C + platinum (PBO arm) in recurrent and/or metastatic (R/M) SCCHN. The primary objective is to evaluate PFS in the HRG-high population (P vs. PBO arms). Methods: This is arandomized, controlled, double-blind first-line study in Europe. Patients aged ≥ 18 years with confirmed R/M SCCHN, ECOG performance status ≤ 1 and documented HRG expression (per archived or fresh biopsies) are eligible. The primary efficacy endpoint is PFS. Secondary endpoints include overall survival, overall response rate, pharmacokinetics and safety (including human antihuman antibody incidence). Approximately 105 patients will be stratified 2:1 by HRG status (70 high; 35 low), and then randomized 1:1 to the P or PBO arm. All patients will receive either intravenous P (18mg/kg loading dose [LD]; 9mg/kg maintenance dose [MD] every 3 weeks [q3w]) or PBO, and C (400mg/m2 LD; 250mg/m2 MD weekly) + ≤ 6 cycles of cisplatin (100mg/m2 q3w) or carboplatin (area under the curve of 5). Patients demonstrating CR, PR or SD will be treated with P/PBO + C + ≤ 6 cycles platinum for the study duration (until all patients have died or ≥ 13 months postrandomization of last patient); those benefiting may continue treatment uninterrupted in an open-label extension phase until progressive disease, toxicity or withdrawal. Survival status will be obtained ≥ 13 months after discontinuation. The first patient was dosed December 2015 and enrollment is open. Clinical trial information: NCT02633800.
Phase I venetoclax monotherapy for relapsed/refractory multiple myeloma.
Authors: Shaji Kumar, Ravi Vij, Jonathan L. Kaufman, Joseph Mikhael, Thierry Facon, Brigitte Pegourie, Lotfi Benboubker, Cristina Gasparetto, Martine Amiot, Philippe Moreau, Susan Diehl, Stefanie Alzate, Jeremy A Ross, Martin Dunbar, Ming Zhu, Suresh K Agarwal, Joel Leverson, Paulo Cesar Maciag, Maria E. Verdugo, Cyrille Touzeau
Journal: Journal of Clinical Oncology (2016)

8032 Background: The anti-apoptotic protein BCL-2 has been implicated in the survival of multiple myeloma (MM) cells. Venetoclax (VEN) is an oral, highly selective BCL-2 inhibitor, which induces cell death in MM cell lines and primary samples, particularly those with t(11;14), a high BCL-2 and low BCL-XL profile. Methods: In this phase 1 study of VEN monotherapy in relapsed/refractory (R/R) MM, objectives are to evaluate safety, PK, RPTD, and preliminary efficacy. After 2-week dose-ramp-up, VEN was given daily at 300, 600, 900, or 1200 mg in dose escalation (DE) cohorts and 1200 mg in safety expansion (SE). Results: As of 9/17/15, 48 pts were enrolled: 30 DE and 18 SE. Median age was 65; 28 were ISS stage II/III. Median (range) prior therapies: 5 (1–15). 45 had prior bortezomib (32 refractory), 46 lenalidomide (37 refractory), and 40 had SCT. 18 pts had t(11;14). AEs in ≥ 30% of pts were diarrhea (40%), nausea (40%), thrombocytopenia (31%). Grade 3/4 AEs in ≥ 10%: thrombocytopenia (29%), anemia, neutropenia (17% each). SAEs in ≥ 2 pts were sepsis (n = 3), cough, malignant neoplasm progression, and pyrexia (2 each). Median (range) time on VEN was 1.9 (0.2–13.8) months. 33 (69%) pts discontinued (DC): 26 related to PD, 4 due to AEs (worsening shortness of breath, hypokalemia, nausea, lung disorder), 2 withdrew consent, 1 due to death (brain hemorrhage following injury). 5 deaths occurred (3 PD, 1 brain hemorrhage, 1 lung disorder). 2 DLTs were seen at 600 mg (cohort was expanded): epigastric pain, nausea with abdominal pain. Steady state mean Cmax and AUC24 were ~dose proportional at all doses except 900 mg (n = 21). 43 of 48 pts were evaluable for efficacy (table). In CR pts, responses were maintained for 9.7 (600 mg) and 9.0 months (900 mg, ongoing). VGPR was reported for 3 pts, all 1200 mg. Conclusions: VEN monotherapy has a tolerable safety profile in R/R MM. Preliminary efficacy, including CR, and VGPR, support VEN single agent activity in this population, primarily in t(11;14) pts. Clinical trial information: NCT01794520.Best response, n (%) With t(11;14) (n = 17) Without t(11;14) (n = 26) All (n = 43) ORR 4 (24) 1 (4) 5 (12) CR 2 (12) 0 2 (5) VGPR 2 (12) 1 (4)* 3 (7) MR 1 (6) 0 1 (2) SD 5 (29) 12 (46) 17 (40) PD 6 (35) 12 (46) 18 (42) DC before assessment 1 (6) 1 (4) 2 (5) *Pt has translocation of chromosome 14 with unknown partner
Benefit of chemotherapy (CT) in patients (pts) with Merkel cell carcinoma (MCC) with distant metastases (mets) and visceral organ involvement.
Authors: Angeline J. Sabol, Svetomir Markovic, Clark Otley, Katharine Andress Rowe Price
Journal: Journal of Clinical Oncology (2016)

e21000 Background: MCC is a rare skin cancer with a propensity for distant mets, yet the ability of palliative CT to impact survival is unknown. Methods: Pts with MCC were identified from an institutional database from 1990-2015. Demographic and clinical data were abstracted from the medical record. Pts with distant mets were analyzed for survival. Genomic testing by Foundation Medicine, if performed, is reported. Results: 205 pts with MCC were identified; 43 (21%) developed distant mets. Median age was 69 years (range 52-93, 36 male). Median time of follow up was 1.7 years. For initial treatment, 41 pts had surgery and 30 pts had adjuvant radiotherapy. Location of distant mets included: skin (n = 26), liver (n = 17), distant lymph nodes (n = 10),), bone (n = 7) lung (n = 2), heart (n = 2), kidney (n = 1), stomach (n = 1), pancreas (n = 1), and testes (n = 1). Visceral mets were seen in 23 pts. 24 pts received chemotherapy for metastatic disease and 19 did not. CT regimens were platinum/etoposide (n = 21) and doxorubicin, cyclophosphamide, and vincristine (n = 7). At last follow-up, 16 pts were alive and 27 were dead. For the whole cohort, 2-year overall survival (OS) was not increased with the use of CT (41% no CT, 68% with CT; p = 0.222). 2-year OS was 61% for pts without visceral involvement and 49% for pts with visceral mets (p = 0.127). However, 2-year OS of pts with visceral mets who received CT was better than those pts with visceral mets who did not receive CT (77% versus 0%; p = 0.0016). Genomic testing was available for 5 pts. Two pts had no targetable mutations. One pt had a mutation in HRAS G12S. One pt had a PTEN R335 mutation and was treated with temsirolimus but had to stop due to low blood counts after 2 doses so response could not be assessed. One pt had several genomic alterations: CD274 (PD-L1) amplification, JAK2 amplification, KDR G49E, PDCD1LG2 (PD-L2 amplification, and PIK3R2 W165. Conclusions: CT may have a survival benefit in pts with MCC with distant visceral mets. Further genomic testing is needed to inform the role of targeted therapies for pts with metastatic MCC.
Antiplatelet Therapy After Coronary Artery Bypass Grafting
Authors: Makoto Mori, Arnar Geirsson
Journal: JAMA (2018)

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Does patient preference for sexual function preservation impact treatment choice in prostate cancer? Analysis of a population-based cohort.
Authors: James Richard Broughman, Ramsankar Basak, Deborah S Usinger, Kiayni Spearman, Ronald C. Chen
Journal: Journal of Clinical Oncology (2016)

e18093 Background: Prostate cancer patients face several treatment options which vary in their impact on sexual function: active surveillance (least), radiotherapy, and radical prostatectomy (most). In a population-based, prospective cohort of men with newly-diagnosed prostate cancer, we examined whether patient preference for sexual function preservation and baseline sexual function status were associated with treatment choice. Methods: In collaboration with the North Carolina Cancer Registry, 1147 patients were enrolled before treatment from 2011 to 2013 from across the state and followed prospectively. Study staff collected patient-reported treatment preferences (including “preserving your sexual function is…very important, somewhat important, not important”) and pre-treatment quality of life using the validated Prostate Cancer Symptom Indices (PCSI). Per PCSI, each patient was categorized as having normal, intermediate, or poor baseline sexual function. Treatment received was abstracted from medical records. Multivariable logistic regression adjusted for age, race, cancer risk group, marital status, insurance, education and income. Results: Median age was 67 years. 53% of patients indicated preserving sexual function was “very important” – this varied significantly by baseline function: normal (67%), intermediate (58%), and poor (40%). In each group, treatments for patients who indicated “very important” to preserve sexual function were no different than those who indicated this to be somewhat/not important (Table, p = .23). Multivariable analysis showed no association between patient preference and treatment (p = .88). Conclusions: Patient preference to preserve sexual function has little impact on treatment choice in localized prostate cancer. Percentage of patients receiving each treatment modality based on baseline function and preference. Baseline Sexual Function Very important to preserve sexual function Active Surveillance (%) Radiotherapy (%) Radical Prostatectomy (%) Other Treatments (%) Normal Yes (N = 226) 26 24 49 1 No (N = 112) 31 22 46 1 Intermediate Yes (N = 177) 31 25 43 1 No (N = 129) 17 33 47 4 Poor Yes (N = 202) 24 38 35 3 No (N = 301) 30 36 29 5