scholarly journals Effectiveness and toxicity of lenvatinib in refractory thyroid cancer: Dutch real-life data

2020 ◽  
Vol 182 (2) ◽  
pp. 131-138 ◽  
Author(s):  
M D Aydemirli ◽  
E Kapiteijn ◽  
K R M Ferrier ◽  
P B Ottevanger ◽  
T P Links ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Clinical Practice ◽  
Gallbladder Disease ◽  
Real Life ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Eligibility Criteria ◽  
Real Life Situation ◽  
Select Trial

Objective The SELECT trial showed progression-free survival (PFS) benefit for lenvatinib for advanced radioiodine-refractory differentiated thyroid cancer (RAI-refractory or RR-DTC) patients, on which current clinical practice is based. We assessed whether the effectiveness and toxicity of lenvatinib in real-life clinical practice in the Netherlands were comparable to the pivotal SELECT trial. Methods From three Dutch centres Electronic Health Records (EHRs) of patients treated in the lenvatinib compassionate use program or as standard of care were reviewed and checked for SELECT eligibility criteria. Baseline characteristics, safety, and efficacy measures were compared and PFS and overall survival (OS) were calculated. Furthermore, PFS was compared to estimates of PFS reported in other studies. Results A total of 39 DTC patients with a median age of 62 years were analysed. Of these, 27 patients (69%) did not fulfil the SELECT eligibility criteria. The most common grade ≥3 toxicities were hypertension (n = 11, 28%), diarrhoea (n = 7, 18%), vomiting (n = 4, 10%), and gallbladder disease (n = 3, 8%). Median PFS and median OS were 9.7 (95% confidence interval (CI): 4.0–15.5) and 18.3 (95% CI: 4.9–31.7) months, respectively, response rate was 38% (95% CI: 23–54%). PFS in the Dutch real-life situation was comparable to previous real-life studies, but inferior to PFS as shown in the SELECT trial (P = 0.04). Conclusions PFS in our non-trial population was significantly shorter than in the SELECT trial population. In the interpretation of results, differences in the real-life population and the SELECT study population regarding patient characteristics should be taken into account.

scholarly journals Professionals’, patients’ and families’ views on the use of opioids for chronic breathlessness: A systematic review using the framework method and pillar process

2021 ◽  
pp. 026921632110321
Author(s):  
Florence Reedy ◽  
Mark Pearson ◽  
Sarah Greenley ◽  
Joseph Clark ◽  
David C Currow ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Practice ◽  
A Priori ◽  
Synthesis Method ◽  
Patient Characteristics ◽  
Severe Illness ◽  
Pharmacological Interventions ◽  
Eligibility Criteria ◽  
Treatment Regimens ◽  
Appraisal Tool

Background: In combination with non-pharmacological interventions, opioids may safely reduce chronic breathlessness in patients with severe illness. However, implementation in clinical practice varies. Aim: To synthesise the published literature regarding health professionals’, patients’ and families’ views on the use of opioids for chronic breathlessness, identifying issues which influence implementation in clinical practice. Design: Systematic review and synthesis using the five-stage framework synthesis method. Data sources: Three electronic databases (MEDLINE, Embase via OVID, ASSIA via Proquest) were searched (March 2020) using a predefined search strategy. Studies were also citation chained from key papers. Papers were screened against a priori eligibility criteria. Data were extracted from included studies using the framework synthesis method. Qualitative and quantitative data were synthesised using the pillar process. Included studies were critically appraised using the Mixed-Methods Appraisal Tool. Results: After de-duplication, 843 papers were identified. Following screening, 22 studies were included. Five themes were developed: (i) clinician/patient characteristics, (ii) education/knowledge/experience, (iii) relationship between clinician/family, (iv) clinician/patient fear of opioids and (v) regulatory issues. Conclusions: There are significant barriers and enablers to the use of opioids for the symptomatic reduction of chronic breathlessness based on the knowledge, views and attitudes of clinicians, patients and families. Clinicians’ interactions with patients and their families strongly influences adherence with opioid treatment regimens for chronic breathlessness. Clinicians’, patients’ and families’ knowledge about the delicate balance between benefits and risks is generally poor. Education for all, but particularly clinicians, is likely to be a necessary (but insufficient) factor for improving implementation in practice.

Economic aspects of nivolumab in non-small cell lung cancer (NSCLC): Lessons from real life.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18322-e18322
Author(s):  
Elizabeth Dudnik ◽  
Laila Roisman ◽  
Jair Bar ◽  
Nir Peled ◽  
Ariel Hammerman ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Market Price ◽  
Real Life ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Routine Practice ◽  
Duration Of Treatment ◽  
Total Treatment Cost ◽  
Group B ◽  
Ecog Ps

e18322 Background: Novel immunotherapy agents' costs have a significant impact on healthcare system budgets. Aside from the cost per dose of the compound, the total treatment cost (TTC) is affected by the duration of treatment (DOT). DOT in real life may differ significantly from that observed in the randomized clinical trials because of the differences in baseline patient characteristics and treatment patterns. Methods: Advanced NSCLC patients (pts) (n=192) treated with nivolumab 3mg/kg q2w (expanded access program/standard of care) at five Israeli cancer centers between January 2015 and March 2016 were included in the analysis. DOT and TTC were assessed in 2 groups (group A: ECOG PS 0/1, n=92; group B: ECOG PS ≥2, n=100). In addition, response for a subgroup of 49 pts was evaluated by RECIST, v.1.1. In this subgroup, DOT and TTC of treatment (Tx) beyond progression (PD) were assessed as well. Nivolumab cost per dose was calculated for a 78 kg pt based on current market price in Israel: 3 mg/kg X 78 kg = 240 mg = 11,250 NIS (2,993 USD). Results: Pt baseline characteristics: median age 67y (range, 41-99); males 68%; smokers 77%; ECOG PS ≥2 52%; Non-squamous/Squamous/NA 78%/19%/3%. 27% of pts continued nivolumab at the time of last follow-up. DOT and TTC are presented in the table below. Conclusions: DOT and TTC are similar for ECOG PS 0/1 and ECOG PS ≥2 pts. Tx beyond PD increases the TTC by 32%. These facts should be taken into consideration when evaluating budget impact of novel immunotherapy agents' implementation into routine practice. [Table: see text]

PAzopanib as first line in MEtastatic RCC patients: A “real-world” ITalian experience (PAMERIT study)—Preliminary results.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 611-611
Author(s):  
Alessandra Mosca ◽  
Ugo De Giorgi ◽  
Giuseppe Procopio ◽  
Umberto Basso ◽  
Giacomo Carteni ◽  
...  
Keyword(s):  
Real World ◽  
Poor Prognosis ◽  
Cell Cancer ◽  
Safety Data ◽  
Real Life ◽  
Rank Correlation ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Good Prognosis ◽  
Real World Data

611 Background: Pazopanib (Pazo) became a standard of care in metastatic renal cell cancer (mRCC) patients (pts) based on 2 prospective trials, but “real life” data are slight. Methods: We retrospectively analyzed clinical outcomes in a large series of mRCC pts routinely treated with 1st line Pazo, among 39 Italian Centers. Descriptive statistics has been performed using Chi-Square and Pearson rank correlation test. Progression-free survival (PFS), overall survival (OS) and safety data are still under investigation. Results: 474 mRCC pts have been collected and divided in 4 age categories: 1) ≤50 yrs old (9.4%); 2) 51-64 yrs old (32.6%); 3) 65-74 yrs old (33.0%); 4) ≥75 yrs old (25.0%). According to Heng score, 25.6%, 48.4% and 10.4% pts had good, intermediate and poor prognosis, respectively, without correlations with age (p = 0.128). Clear cell was the most represented histology (87.3%), independently from age (p = 0.556). 84.6% pts underwent nephrectomy, mainly younger pts (p = 0.000). Pazo initial daily dose was 800 mg in 76.5% pts, 600 mg in 10.8% pts and 400 mg in 12.7% pts, with a significant dose reduction in elderly pts: Pazo 800 was administered in 86.7% of ≤50 yrs old pts and in 54.2% of ≥75 yrs old pts (p = 0.000). Complete (CR)/partial response (PR), stable and progressive disease have been recorded in 37%, 39.5% and 23.5% pts, respectively. Radiological response directly correlated either with age (CR/PR in 55.6% of ≤50 yrs old pts vs 28.8% of ≥75 yrs old pts; p = 0.009) and with Heng score (CR/PR in 47.1% of good prognosis pts vs 24.5% of poor prognosis pts; p = 0.002). Conclusions: “Real world” data showed that younger (≤50 yrs old) mRCC pts more frequently underwent nephrectomy, received Pazo 800 mg daily and obtained CR/PR, with respect to elderly pts (≥75 yrs old). CR/PR to Pazo is associated with good prognosis. PFS and OS will be provided.

scholarly journals Efficacy and tolerability of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer: results of a multicenter observational study in the Russian Federation

2020 ◽  
Vol 10 (1) ◽  
pp. 65-72
Author(s):  
E. V. Borodavina ◽  
P. A. Isaev ◽  
A. Yu. Shurinov ◽  
P. O. Rumyantsev ◽  
V. V. Krylov ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Clinical Practice ◽  
Russian Federation ◽  
Differentiated Thyroid Cancer ◽  
Progression Free Survival ◽  
Good Tolerability ◽  
Study Objective ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
The Russian Federation

Background. The implementation of tyrosine kinase inhibitors into clinical practice improved treatment outcomes in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Lenvatinib is recommended as a first-line drug for these patients. The study objective is to analyze clinical experience with lenvatinib in patients with RR-DTC in the Russian Federation. Materials and methods. The data from 18 clinical sites in Russia was analyzed for the period December 2015 and September 2019. Seventyseven patients with histologically verified DTC, proven resistance to radioactive iodine therapy, and tumor progression (according to the Response Evaluation Criteria In Solid Tumors 1.1 criteria) were included in the study. Results.Median progression-free survival in patients included into analysis (n = 72) was 26.1 months. In patients who responded to therapy (including those with partial and complete response), median progression-free survival reached 36.2 months, which is higher than that reported in the updated results of the SELECT study (33.1 months). Lenvatinib-associated adverse events (AEs) were observed in 87 % of patients. Severe AEs were registered in 18.2 % of participants. In 6.5 % of cases, AEs lead to lenvatinib cessation; in 74 % of cases, AEs required dose reduction.Conclusion. Our findings suggest high efficacy and good tolerability of lenvatinib in patients with RR-DTC in routine clinical practice in the Russian Federation.

The effect of cytoreductive radiofrequency ablation (cRFA) on results of therapy with sunitinib or interferon-alpha (IFN) in metastatic renal cell carcinoma (RCC) patients with a small primary tumor.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 414-414
Author(s):  
Ilya Tsimafeyeu ◽  
Bin Chung ◽  
Janie S. Zart ◽  
Keyword(s):  
Primary Tumor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Good Prognosis ◽  
Eligibility Criteria ◽  
Small Primary ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
Metastatic Rcc

414 Background: At least 5% of the patients (pts) with small primary RCC initially present with metastasis. The main objective of this trial was to evaluate the role of cRFA in metastatic RCC pts with small primary tumor treated with immuno- or targeted therapy. Methods: Three parallel single-arm prospective studies were conducted. Eligibility criteria were nearly identical for all trials, and included histopathologically confirmed RCC; metastatic measurable disease; size of primary tumor ≤5 cm; good prognosis by MSKCC model; no previous therapy. Study 1: Pts were treated with percutaneous cRFA under CT guide and following IFN, 9 MIU, s.c, 3 tiw. Study 2: Pts received cRFA and following sunitinib in repeated 6-week cycles of 50 mg/day for 4 weeks, followed by 2 weeks off. Study 3: Pts with unresected primary RCC received sunitinib alone. The primary endpoint was a 33% increase in progression-free survival (PFS) over expected 5 months in study 1 and over expected 11 months in studies 2-3 (power 80%; significance .05). Sample size was 38 pts for each study. Results: Studies were comparable by baseline patient characteristics (age, gender, histology, ECOG PS, number of metastatic sites, primary tumor size). Efficacy data for 114 evaluable pts showed an objective response rate (ORR) of 8% (95% CI 4.5, 10.5) for study 1, 28.9% (95% CI 15.2, 34) for study 2, and 31.6% (95% CI 20.3, 38.9) for study 3; median PFS of 9.1 (95% CI 6.9, 10.2), 13.4 (95% CI 9.8, 14), and 12.7 (95% CI 11.3, 13.5) months for studies 1-3, respectively. ORR and PFS were significantly higher in sunitinib trials comparing with study 1 (P<.01 all differences); no differences were found between studies 2 and 3 (ORR, P=.1; PFS, P=.6). The study 1 met its primary end point, showing that PFS was significantly increased. There were no unexpected toxicities of medical treatment and complications of cRFA. Conclusions: cRFA is a safe and effective approach for select patients with metastatic RCC treated with immunotherapy. Cytoreductive ablative technique did not improve PFS in pts treated with sunitinib. Sunitinib was effective in metastatic RCC pts with unresected small primary tumor.

AcceleRET Lung: A phase III study of first-line pralsetinib in patients (pts) with RET-fusion+ advanced/metastatic non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS9633-TPS9633 ◽  
Author(s):  
Benjamin Besse ◽  
Enriqueta Felip ◽  
Corinne Clifford ◽  
Melinda Louie-Gao ◽  
Jennifer Green ◽  
...  
Keyword(s):  
Phase 1 ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Survival Duration ◽  
First Line ◽  
Open Label ◽  
Eligibility Criteria ◽  
Multiple Tumor ◽  
Platinum Based Chemotherapy

TPS9633 Background: RET gene fusions have been identified as oncogenic drivers in multiple tumor types, including 1-2% of NSCLC, but no selective RET inhibitors are approved for use. The investigational RET inhibitor, pralsetinib, potently and selectively targets oncogenic RET alterations, including those that confer resistance to multikinase inhibitors. In the registration-enabling phase 1/2 study (ARROW; NCT03037385), pts with RET-fusion+ NSCLC treated with 400 mg once daily (QD) of pralsetinib (N = 80) after platinum-based chemotherapy achieved an overall response rate (ORR) of 61% (95% CI 50, 72; 2 responses pending confirmation) per independent central review. In addition, a promising ORR of 73% (all centrally confirmed responses) was attained in the treatment naïve cohort (N = 26). Most treatment-related adverse events were grade 1-2 across the entire safety population treated at 400 mg QD (N = 354). AcceleRET Lung, an international, open-label, randomized, phase 3 study, will evaluate the efficacy and safety of pralsetinib versus standard of care (SOC) for first-line treatment of advanced/metastatic RET fusion+ NSCLC (NCT04222972). Methods: Approximately 250 pts with metastatic RET-fusion+ NSCLC will be randomized 1:1 to oral pralsetinib (400 mg QD) or SOC (non-squamous histology: platinum/pemetrexed ± pembrolizumab followed by maintenance pemetrexed ± pembrolizumab; squamous histology: platinum/gemcitabine). Stratification factors include intended use of pembrolizumab, history of brain metastases, and ECOG PS. Key eligibility criteria include no prior systemic treatment for metastatic disease; RET-fusion+ tumor by local or central assessment; no additional actionable oncogenic drivers; no prior selective RET inhibitor; measurable disease per RECIST v1.1. Pts randomized to SOC will be permitted to cross-over to receive pralsetinib upon disease progression. The primary endpoint is progression-free survival (blinded independent central review; RECIST v1.1). Secondary endpoints include ORR, overall survival, duration of response, disease control rate, clinical benefit rate, time to intracranial progression, intracranial ORR, safety/tolerability and quality of life evaluations. Recruitment has begun with sites (active or planned) in North America, Europe and Asia. Clinical trial information: NCT04222972 .

scholarly journals Development, validation, and implementation of biomarker testing in cardiovascular medicine state-of-the-art: proceedings of the European Society of Cardiology—Cardiovascular Round Table

2020 ◽  
Author(s):  
Perry Elliott ◽  
Martin R Cowie ◽  
Jennifer Franke ◽  
André Ziegler ◽  
Charalambos Antoniades ◽  
...  
Keyword(s):  
Clinical Practice ◽  
New Technologies ◽  
Biomarker Discovery ◽  
Real Life ◽  
High Sensitivity ◽  
Standard Of Care ◽  
Round Table ◽  
Current Standard ◽  
Development Pathway ◽  
Regulatory Standards

Abstract Many biomarkers that could be used to assess ejection fraction, heart failure, or myocardial infarction fail to translate into clinical practice because they lack essential performance characteristics or fail to meet regulatory standards for approval. Despite their potential, new technologies have added to the complexities of successful translation into clinical practice. Biomarker discovery and implementation require a standardized approach that includes: identification of a clinical need; identification of a valid surrogate biomarker; stepwise assay refinement, demonstration of superiority over current standard-of-care; development and understanding of a clinical pathway; and demonstration of real-world performance. Successful biomarkers should improve efficacy or safety of treatment, while being practical at a realistic cost. Everyone involved in cardiovascular healthcare, including researchers, clinicians, and industry partners, are important stakeholders in facilitating the development and implementation of biomarkers. This article provides suggestions for a development pathway for new biomarkers, discusses regulatory issues and challenges, and suggestions for accelerating the pathway to improve patient outcomes. Real-life examples of successful biomarkers—high-sensitivity cardiac troponin, T2* cardiovascular magnetic resonance imaging, and echocardiography—are used to illustrate the value of a standardized development pathway in the translation of concepts into routine clinical practice.

scholarly journals Daily Practice Managing Resistant Multiple Sclerosis Spasticity With Delta-9-Tetrahydrocannabinol: Cannabidiol Oromucosal Spray: A Systematic Review of Observational Studies

2019 ◽  
Vol 11 ◽  
pp. 117957351983199 ◽  
Author(s):  
Katja Akgün ◽  
Ute Essner ◽  
Cordula Seydel ◽  
Tjalf Ziemssen
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Clinical Practice ◽  
Real World ◽  
Observational Studies ◽  
Rating Scale ◽  
Real Life ◽  
Daily Practice ◽  
Patient Characteristics ◽  
Numeric Rating Scale

Background/purpose: Spasticity is one of the most common symptoms in people with multiple sclerosis (MS). Conventional anti-spasticity agents have limitations in their efficacy and tolerability. Delta-9-tetrahydrocannabinol: cannabidiol (THC:CBD) spray, a cannabinoid-based medicine, is approved as an add-on therapy for MS spasticity not adequately controlled by other anti-spasticity medications. The results from randomized controlled trials (RCTs) have demonstrated a reduction in the severity of spasticity and associated symptoms. However, RCTs do not always reflect real-life outcomes. We systematically reviewed the complementary evidence from non-interventional real-world studies. Methods: A systematic literature review was conducted to identify all non-RCT publications on THC:CBD spray between 2011 and 2017. Data on study design, patient characteristics, effectiveness, and safety outcomes were extracted from those publications meeting our inclusion criteria. Results: In total, we reviewed 14 real-world publications including observational studies and treatment registries. The proportion of patients reaching the threshold of minimal clinical important difference (MCID), with at least a 20% reduction of the spasticity Numeric Rating Scale (NRS) score after 4 weeks ranged from 41.9% to 82.9%. The reduction in the mean NRS spasticity score after 4 weeks was maintained over 6-12 months. The average daily dose was five to six sprays. Delta-9-tetrahydrocannabinol: cannabidiol was well tolerated in the evaluated studies in the same way as in the RCTs. No new or unexpected adverse events or safety signals were reported in everyday clinical practice. Conclusions: The data evaluated in this systematic review provide evidence for the efficacy and safety of THC:CBD in clinical practice and confirm results obtained in RCTs.

Three versus four cycles of neoadjuvant gemcitabine cisplatin for muscle invasive bladder cancer (MIBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16524-e16524
Author(s):  
Catherine Kendall Major ◽  
Michael Brandon Williams ◽  
Mark T. Fleming
Keyword(s):  
Radical Cystectomy ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Intention To Treat ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Muscle Invasive ◽  
Dose Dense

e16524 Background: The standard of care for MIBC is neoadjuvant (NAC) cisplatin-based chemotherapy with either 3-4 cycles of dose dense MVAC or 4 cycles of gemcitabine/cisplatin (GC) followed by radical cystectomy. However, due to toxicity some patients are unable to complete intention to treat full course chemotherapy. We aim to identify any variation in overall survival (OS) and progression-free survival (PFS) with 3 vs 4 cycles of neoadjuvant GC in the setting of miUCB. We hypothesize that there will be a statistically significant difference in OS and PFS with three vs four cycles of neoadjuvant GC. Methods: A consecutive retrospective chart review of patients with MIBC treated with three or four cycles of neoadjuvant cisplatin-based chemotherapy from 2009-2020 was performed. R Studio was used to generate Kaplan-Meier curves representing OS and PFS with p-values. Results: One hundred and twenty-one patients were identified. Patient characteristics are described in the table below. Eighty-six patients received 4 cycles of GC and thirty-five patients received 3 cycles. Ninety-five patients proceeded to cystectomy: 93 received a radical cystectomy, 1 received a partial cystectomy, and 1 was aborted due to positive lymph nodes. There was a statistically significant difference in OS between those who got 3 or 4 cycles (p=0.03) and PFS (p=0.014). Median OS for those who got 3 cycles and 4 cycles was 52 months and 92 months respectively. Conclusions: Toxicity can preclude patients from receiving four cycles of GC and this study demonstrates a significant difference in overall OS and PFS between those who receive 3 vs 4 cycles of GC.[Table: see text]

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