scholarly journals Analisi di costo di pemetrexed vs docetaxel nel trattamento di seconda linea del carcinoma polmonare non a piccole cellule

2005 ◽  
Vol 6 (2) ◽  
pp. 119-126
Author(s):  
Roberto Ravasio
Keyword(s):  
Adverse Events ◽  
Cost Analysis ◽  
Cost Utility ◽  
Phase Iii ◽  
Chemotherapy Drugs ◽  
Study Results ◽  
Previously Treated ◽  
The Mean ◽  
The Difference ◽  
Mean Cost

OBJECTIVES: to compare costs of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy paying special attention to the adverse events. MATERIALS AND METHODS: a cost analysis was carried out performing comparison between pemetrexed and docetaxel. Clinical data (overall survival) and resource consumption (chemotherapy drugs, G-CSF, and hospitalizations due to adverse events) were obtained from a randomized phase III trial. The economic evaluation was based on direct costs using local Italian unit costs (euro 2005). The perspective was the National Health Service’s. RESULTS: the study results showed that mean survival of pemetrexed (8,3 months; 0,69 years) was higher than mean survival of docetaxel (7,9 months; 0,66 years). The mean cost of treatment with pemetrexed was 8.684,26 euros and with docetaxel was 6.182,87 euros. This difference was nearly offset by the difference in the costs of adverse events: the mean cost of adverse events due to chemotherapy treatment with pemetrexed (493,93 euros) turned out to be lower than with docetaxel (2.394,34 euros). CONCLUSION: the present cost-analysis could be a stable ground for a further cost-utility analysis, aimed at reaching a more cost-effectiveness management of the chemotherapy-related adverse effects in patients with NSCLC.

Iodixanol in Abdominal Digital Subtraction Angiography

1993 ◽  
Vol 34 (3) ◽  
pp. 242-245 ◽  
Author(s):  
K. Singh ◽  
R. Sundgren ◽  
B. Bolstad ◽  
L. Björk ◽  
M. Lie
Keyword(s):  
Adverse Events ◽  
Clinical Importance ◽  
Diagnostic Information ◽  
Phase Iii ◽  
Digital Subtraction ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Phase Iii Trial ◽  
The Mean ◽  
The Difference

The safety, tolerability and efficacy of iodixanol 270 mg I/ml were compared to those of iohexol 300 mg I/ml in a double-blind, randomized, parallel abdominal intra-arterial DSA phase III trial. Fifty-nine patients were included in the trial; 39 patients received iodixanol and 20 received iohexol. The mean volume of iodixanol administered was 235.8 ml (0.93 g I/kg b.w.) while the mean volume of iohexol was 254.7 ml (1.10 g I/kg b.w.). No differences in diagnostic information and radiographic density were apparent in spite of the difference in the concentration of iodine. No serious adverse events occurred. Four patients (10%) in the iodixanol group and 2 (10%) in the iohexol group experienced adverse events. Eight percent of the injections of iodixanol promoted discomfort, compared to 12%) of the injections of iohexol. An increase in S-urea and S-creatinine was seen with both agents the first day after injection, but appeared to be less pronounced with iodixanol than with iohexol. Other serum tests revealed no changes of clinical importance. Both iodixanol and iohexol were found to be effective, safe and well tolerated contrast media for abdominal intra-arterial DSA.

scholarly journals Private Practice Pricing in the Birmingham Region

2019 ◽  
Vol 8 (1) ◽  
pp. 34-37
Author(s):  
Anant Bakshi ◽  
Raeesa Khan ◽  
Bilal Ahmed
Keyword(s):  
Dental Implants ◽  
Average Cost ◽  
Dental Treatment ◽  
Dental Procedure ◽  
Dental Procedures ◽  
Dental Intervention ◽  
The Mean ◽  
The Difference ◽  
Mean Cost ◽  
Insight Into

This study was carried out to evaluate the difference in prices for dental treatments carried out privately in general dental practice within the Birmingham area. Ten different practices were chosen at random, which were spread across Birmingham, in order to get a better insight into the differences across the districts. Their prices for pre-determined dental procedures were procured off the practices’ respective websites or through telephoning. The findings of this study have shown a wide variation in prices for each dental procedure, with the greatest variation in prices between practices being £850 for dental implants. The procedures with the lowest average cost were fissure sealants at £23.14. The procedure with the highest average cost was dental implants at £2,261.11. This study also showed that as more dental treatment was required, the mean cost for the dental intervention increased, regardless of the tooth being treated.

scholarly journals Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1

2016 ◽  
Vol 34 (25) ◽  
pp. 3005-3013 ◽  
Author(s):  
Matthew Smith ◽  
Johann De Bono ◽  
Cora Sternberg ◽  
Sylvestre Le Moulec ◽  
Stéphane Oudard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Specific Antigen ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Bone Biomarkers ◽  
End Point ◽  
Castration Resistant ◽  
Previously Treated

Purpose Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. Patients and Methods Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. Results A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post–random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). Conclusion Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes.

scholarly journals Lactulose versus lactitol in acute hepatic encephalopathy (HE).

2020 ◽  
Vol 27 (08) ◽  
pp. 1595-1601
Author(s):  
Shahid Rasool ◽  
Salman Azhar ◽  
Talha Munir ◽  
Mian Sajjad Ahmad ◽  
Rizwan Abbas ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Controlled Trial ◽  
P Value ◽  
Chi Square ◽  
Female Ratio ◽  
Study Results ◽  
Level Of Consciousness ◽  
Acute Hepatic Encephalopathy ◽  
The Mean ◽  
The Difference

Hepatic encephalopathy (HE), a syndrome observed in some patients with cirrhosis, with depressed level of consciousness. Lactulose as well as lactitol has been used in the treatment of HE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects and better tolerated. However, literature showed equal efficacy of both drugs. So we conducted this trial to find better drug to implement its use in future. Objective: To compare the effectiveness of lactulose and lactitol in patients with acute hepatic encephalopathy. Study Design: Randomized Controlled Trial. Setting: Department of Medicine OPD and Emergency (East, West, North, South), Mayo Hospital, Lahore. Period: 6 Months June 2017 to Dec 2017. Material & Methods: 570 patients were included through non-probability, consecutive sampling after informed consent. Initial grade of HE was assessed and patients were randomly divided in two groups by using lottery method i.e. lactulose or lactitol. Patients were admitted to ward for management and kept under observation for 5 days. After 5 days, HE grades was measured again, then improvement in grade of HE (effectiveness) was measured. All data was entered and analyzed by using SPSS version 21.0. Chi-square was applied to compare both groups for effectiveness taking p-value≤0.05 as significant. Results: In this study the mean age of the patients was 44.22 ±11.81 years, the male to female ratio of the patients was 2.4:1. The mean duration of the cirrhosis of the patients was 3.73±1.61 months. In our study the effectiveness was achieved in 538 (94.39%) patients, out of which 263 cases were from lactulose group and 275 were from lactitol group and the difference was significant (p<0.0.5). Conclusion: Our study results concluded that Lactitol is better choice for the treatment of patients with acute hepatic encephalopathy as compared to lactulose. More efficacy was achieved in lactitol group patients than in lactulose group patients.

scholarly journals Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E–Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study

2021 ◽  
Vol 39 (4) ◽  
pp. 273-284 ◽  
Author(s):  
Josep Tabernero ◽  
Axel Grothey ◽  
Eric Van Cutsem ◽  
Rona Yaeger ◽  
Harpreet Wasan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Standard Of Care ◽  
Braf V600e ◽  
Phase Iii ◽  
Primary Analysis ◽  
Metastatic Setting ◽  
Previously Treated Patients ◽  
Previously Treated

PURPOSE BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with BRAFV600E–mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, binimetinib plus cetuximab (ENCO/BINI/CETUX; triplet) and encorafenib plus cetuximab (ENCO/CETUX; doublet) regimens improved overall survival (OS) and objective response rate (ORR; by blinded central review) versus standard of care. The purpose of this analysis was to report updated efficacy and safety data. METHODS In this open-label, phase III trial, 665 patients with BRAF V600E–mutant mCRC were randomly assigned 1:1:1 to receive triplet, doublet, or control. Primary end points were OS and independently reviewed ORR comparing triplet to control. OS for doublet versus control was a key secondary end point. Updated analyses include 6 months of additional follow-up and ORR for all randomized patients. RESULTS Patients received triplet (n = 224), doublet (n = 220), or control (n = 221). Median OS was 9.3 months (95% CI, 8.2 to 10.8) for triplet and 5.9 months (95% CI, 5.1 to 7.1) for control (hazard ratio [HR], 0.60 [95% CI, 0.47 to 0.75]). Median OS for doublet was 9.3 months (95% CI, 8.0 to 11.3) (HR v control, 0.61 [95% CI, 0.48 to 0.77]). Confirmed ORR was 26.8% (95% CI, 21.1% to 33.1%) for triplet, 19.5% (95% CI, 14.5% to 25.4%) for doublet, and 1.8% (95% CI, 0.5% to 4.6%) for control. Adverse events were consistent with the prior primary analysis, with grade ≥ 3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet, and control, respectively. CONCLUSION In the BEACON CRC study, encorafenib plus cetuximab improved OS, ORR, and progression-free survival in previously treated patients in the metastatic setting compared with standard chemotherapy. Based on the primary and updated analyses, encorafenib plus cetuximab is a new standard care regimen for previously treated patients with BRAF V600E mCRC.

SERUM THYROTROPHIN AND CIRCULATING THYROGLOBULIN ANTIBODIES IN SUBJECTS WITH NON-TOXIC GOITRE AND IN EUTHYROID SUBJECTS WHO HAD UNDERGONE SUBTOTAL THYROIDECTOMY OR RADIOIODINE THERAPY

1973 ◽  
Vol 74 (2) ◽  
pp. 283-295 ◽  
Author(s):  
Ariel Gordin
Keyword(s):  
Radioiodine Therapy ◽  
Elevated Serum ◽  
Mean Value ◽  
Health Examination ◽  
Thyroglobulin Antibodies ◽  
Previously Treated ◽  
The Mean ◽  
The Difference ◽  
Immune Phenomena ◽  
Serum Tsh

ABSTRACT As part of a multiphasic health examination in two regions in the east of Finland, 5492 adult subjects were studied in the province of Kainuu and 2767 in the city of Joensuu. The general prevalence of goitre was 6.0 % in the Kainuu region and 4.2 % in Joensuu and that of frank hypothyroidism 0.3 and 0.4 %, respectively. The serum thyrotrophin (TSH) and circulating thyroglobulin antibodies (TgA) were determined in subjects with non-toxic goitre, in euthyroid subjects who had undergone thyroidectomy or radioiodine therapy, and in matched controls without thyroid disease. In a group of 99 subjects with non-toxic goitre the mean serum TSH (2.9 μU/ml) did not differ from the mean (2.9 μU/ml) of the 40 corresponding controls. Of the 36 subjects who were euthyroid after thyroidectomy without recurrent goitre, 9 had an elevated serum TSH level, and the mean value for this group (5.8 μU/ml) was significantly higher than the mean (3.5 μU/ml) for the 36 controls. Of the 19 subjects with recurrent non-toxic goitre, 2 had an elevated serum TSH level, but the mean value (5.0 μU/ml) was not significantly higher than the mean (3.4 μU/ml) for the 19 controls. Of the 15 subjects who were euthyroid after radioiodine therapy, 4 had an elevated serum TSH level, and the mean value (6.2 μU/ml) was significantly higher than the mean of the 15 controls (3.3 μU/ml). The subjects with non-toxic goitre and positive TgA titres had a significantly higher mean serum TSH than those with goitre but negative TgA titres (3.8 against 2.7 μU/ml). The thyroidectomized subjects without recurrent goitre who had detectable TgA had a significantly lower mean serum TSH than the corresponding subjects who were TgA-negative (4.0 against 6.4 μU/ml). The subjects with recurrent goitre and positive TgA titres had a higher mean TSH level than those without TgA (7.6 against 3.5 μU/ml). but the difference was not significant. Subjects previously treated with radioiodine who had positive TgA titres had a lower mean serum TSH than those who were TgA-negative (4.6 against 6.8 μU/ml), but the difference was not significant. About a fourth of the subjects who were euthyroid after previous thyroidectomy or radioiodine therapy in the present study had elevated serum TSH values, indicating slight thyroid failure. The present results also indicate that auto-immune phenomena may play some part in producing slight thyroid failure in non-toxic goitre, but that other factors are responsible for the elevated TSH values in euthyroid subjects after thyroidectomy or treatment with radioiodine.

A Comparison of Proposed Biosimilar and Originator Filgrastim for the Prevention of Neutropenia in Patients with Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Phase III, Randomized, Double-Blind Trial (The PIONEER study)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5133-5133 ◽  
Author(s):  
Kimberly Blackwell ◽  
Vladimir Semiglazov ◽  
Pedro Gascon ◽  
Roumen Nakov ◽  
Stefan Kramer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Group ◽  
Adverse Events ◽  
Lower Limit ◽  
Study Drug ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Pioneer Study ◽  
The Mean

Abstract Introduction: Biosimilars are biologics which have demonstrated highly similar safety, potency and purity to an originator product. Several biosimilars of recombinant human filgrastim, based on the originator Neupogen®, have become available in Europe since 2008 and are now in clinical use for the prevention of chemotherapy-induced neutropenia and hematopoietic stem cell mobilization. Filgrastim biosimilars are presently being developed for the U.S. market. Study design: A randomized, double-blind, four-group, multi-center phase III non-inferiority trial was performed with breast cancer patients treated with myleosuppressive chemotherapy. The two filgrastim products – proposed biosimilar, EP2006 (“biosimilar”) vs. originator (U.S.-licensed Neupogen®) - were compared regarding efficacy and safety. Patients included: women ≥18 years with histologically-proven breast cancer eligible for neoadjuvant or adjuvant treatment with docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC regimen) given for 6 cycles. Other key inclusion criteria included: Eastern Cooperative Oncology Group performance status ≤2 and adequate bone marrow function. Eligible patients were randomized to 4 groups with 2 of these groups alternating between the biosimilar and the originator filgrastim at the end of each cycle: 1) EP: treatment with EP2006 in all cycles; 2) EPNEU: EP2006 in Cycle 1, alternating between Neupogen and EP2006 in the following cycles; 3) NEUEP: Neupogen in Cycle 1, alternating between EP2006 and Neupogen in the following cycles; 4) NEU: treatment with Neupogen in all cycles. Patients received either biosimilar or originator filgrastim subcutaneously (daily dose of 5 µg/kg body weight) starting on Day 2 of each chemotherapy cycle until the absolute neutrophil count (ANC) recovered to 10×109/L after nadir or up to 14 days. Total duration of the study was 25 weeks: 3 weeks screening, 18 weeks treatment (total 6 cycles, 3 weeks each) and a follow-up visit 4 weeks after the last study drug administration. Primary objective was to assess the efficacy of the biosimilar compared to the originator with respect to mean duration of severe neutropenia (DSN) following Cycle 1 chemotherapy. A one-sided 97.5% confidence interval (CI) for the difference in the mean DSN calculated using ANCOVA model with factors “treatment” and “kind of therapy” and covariates “baseline ANC” was to be considered non-inferior if lower limit of this CI lies entirely above non-inferiority margin of -1 day. All secondary efficacy endpoints and safety endpoints were analyzed descriptively by treatment group. The study was conducted between December 2011 and June 2013. Results: Enrolled were 258 patients in 27 centers, of which 218 patients were randomized to treatment. The baseline characteristics were balanced between different groups. The per-protocol set included 204 patients out of 218 randomized patients. The safety set included 214 patients who received at least one dose of study drug. On average each patient received treatment for 8-9 days per cycle. The mean DSN in Cycle 1 was 1.17±1.11 days (biosimilar) and 1.20±1.02 days (originator); the mean difference in DSN was 0.04 days (97.5% CI, lower limit -0.26 days). The pre-defined non-inferiority criteria were met and the biosimilar was considered non-inferior to the originator filgrastim. The incidence of febrile neutropenia over all 6 cycles chemotherapy was comparably low in all treatment groups (EP: 2/40, 5.0%, EPNEU: 5/45, 11.1%, NEUEP: 1/44, 2.3%, NEU: 0/46, 0.0%). There was no obvious difference in incidences of treatment emergent adverse events between the treatment arms. Twelve patients experienced serious adverse events (EP: 5/53, 9.4% patients; EPNEU: 4/54, 7.4%; NEUEP: 1/55, 1.8%; NEU: 2/52, 3.8%). None of them were study drug related, including one death (in the EP treatment group due to pulmonary embolism). No subjects developed anti-drug antibodies. Conclusion: This large clinical study showed that efficacy and safety of the biosimilar was comparable to the originator filgrastim in prevention of neutropenia in patients with breast cancer. Repeated switching between the biosimilar and the originator filgrastim did not impact efficacy, safety or immunogenicity. Acknowledgment: The authors acknowledge the other investigators of the PIONEER study and acknowledge Gabor Stiegler, Sandoz Biopharmaceuticals for the medical writing. Disclosures Blackwell: Sandoz Biopharmaceuticals: Consultancy. Semiglazov:Sandoz Biopharmaceuticals: Consultancy. Gascon:Sandoz Biopharmaceuticals: Consultancy. Nakov:Sandoz Biopharmaceuticals: Employment. Kramer:Sandoz Biopharmaceuticals: Employment. Schwebig:Sandoz Biopharmaceuticals: Employment. Harbeck:Sandoz Biopharmaceuticals: Consultancy.

PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy

2016 ◽  
Vol 34 (32) ◽  
pp. 3914-3920 ◽  
Author(s):  
Sharlene Gill ◽  
Yoo-Joung Ko ◽  
Christine Cripps ◽  
Annie Beaudoin ◽  
Sukhbinder Dhesy-Thind ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Group Performance ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Life Questionnaire ◽  
Second Line ◽  
European Organization ◽  
Phase Iii Study ◽  
Previously Treated

Purpose The standard of care for second-line therapy in patients with advanced pancreatic cancer after gemcitabine-based therapy is not clearly defined. The CONKO-003 phase III study reported a survival benefit with second-line fluorouracil (FU) and oxaliplatin using the oxaliplatin, folinic acid, and FU (OFF) regimen. 1 PANCREOX was a phase III multicenter trial to evaluate the benefit of FU and oxaliplatin administered as modified FOLFOX6 (mFOLFOX6; infusional fluorouracil, leucovorin, and oxaliplatin) versus infusional FU/leucovorin (LV) in this setting. Patients and Methods Patients with confirmed advanced pancreatic cancer who were previously treated with gemcitabine therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. A total of 108 patients were randomly assigned to receive biweekly mFOLFOX6 or infusional FU/LV until progression. Progression-free survival (PFS) was the primary end point. Results Baseline patient characteristics were similar in both arms. No difference was observed in PFS (median, 3.1 months v 2.9 months; P = .99). Overall survival (OS) was inferior in patients assigned to mFOLFOX6 (median, 6.1 months v 9.9 months; P = .02). Increased toxicity was observed with the addition of oxaliplatin, with grade 3/4 adverse events occurring in 63% of patients who received mFOLFOX6 and 11% of those who received FU/LV. More patients in the mFOLFOX6 arm withdrew from study due to adverse events than in the FU/LV arm (20% v 2%), whereas the use of postprogression therapy was significantly higher in the FU/LV arm (25% v 7%; P = .015). No significant differences were observed in time to deterioration on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 global health scale. Conclusion No benefit was observed with the addition of oxaliplatin, administered as mFOLFOX6, versus infusional FU/LV in patients with advanced pancreatic cancer previously treated with first-line gemcitabine.

scholarly journals Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results

2021 ◽  
pp. 135245852110379
Author(s):  
Ralf Gold ◽  
Douglas L Arnold ◽  
Amit Bar-Or ◽  
Robert J Fox ◽  
Ludwig Kappos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Dimethyl Fumarate ◽  
Phase Iii ◽  
Study Results ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Dimethyl fumarate (DMF) demonstrated favorable benefit–risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension. Objective: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE. Methods: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0–2), then DMF (Years 3–10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years. Results: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04–10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF ( n = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120–0.169)), while for PBO/DMF ( n = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0–2 years, 0.330 (95% CI, 0.266–0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118–0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening. Conclusion: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF’s positive benefit/risk profile for long-term RRMS treatment.

Ipilimumab retreatment following induction therapy: The expanded access program (EAP) experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9041-9041 ◽  
Author(s):  
Kim Allyson Margolin ◽  
Omid Hamid ◽  
Jeffrey S. Weber ◽  
Anna C. Pavlick ◽  
F. Stephen Hodi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Clinical Benefit ◽  
Objective Response ◽  
Initial Therapy ◽  
Phase Iii ◽  
Delayed Response ◽  
Serious Adverse Events ◽  
Study Results ◽  
Grade 3

9041 Background: Phase III study MDX010-020 for patients (pts) with advanced melanoma showed that retreatment (ReRx) with ipilimumab (Ipi) upon disease progression could result in further clinical benefit (Hodi et al. NJEM 2010). The Ipi EAP (CA184-045), conducted from 3/2010 to 3/2011, allowed ReRx with Ipi for a subset of pts with progression after benefit from their initial Ipi (SD for ≥3 months or objective response). Methods: Pts with unresectable stage III/IV melanoma who progressed on ≥1 systemic therapies or had no alternative treatment options were eligible for the EAP. Pts who received 3 mg/kg Ipi i.v. q 3 wks up to 4 doses on the EAP were eligible for ReRx using the same regimen if they had not experienced unacceptable toxicity requiring Ipi discontinuation (e.g., grade 4 any severe adverse events (AEs), grade 3/4 immune-related AEs (excluding endocrinopathies)), and had disease progression after clinical benefit defined as ≥3 months SD or objective response, or delayed response following progressive disease not requiring a different interval therapy. Endpoints of this retrospective analysis were clinical benefit defined by objective response or SD ≥3 months and toxicities measured by occurrence of serious adverse events (SAEs), irAEs, or death on study. Results: 108/2155 pts (5%) met the eligibility criteria for ReRx. Among these 108 pts, grade 3 drug-related SAEs during initial therapy were endocrinopathies only (4%). During ReRx, grade 3 drug-related SAEs, all <2%, were colitis, diarrhea, GI hemorrhage, fatigue and dehydration, similar to the toxicities of Ipi in the full EAP cohort of 2155 pts. Three pts (3%) of the 108 in this ReRx cohort had drug-related GI SAEs leading to discontinuation of Ipi. Among these pts who underwent ReRx, the median OS from the 1st initial therapy dose was 21.1 months. Conclusions: In this analysis of EAP pts who experienced benefit from initial Ipi therapy (including those with durable SD who subsequently progressed) and received ReRx with Ipi, no new safety signals were identified. The potential benefit of Ipi ReRx on OS will be prospectively evaluated in an ongoing phase II study in which pts who qualify are randomized to Ipi ReRx or physician’s choice alternative therapy. Clinical trial information: NCT00495066.

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