FRI0022 Anemia is an Independent Predictor of Radiographic Damage Progression in Anti-TNF-Treated Rheumatoid Arthritis Patients from Two Large Phase III Trials

2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 426.2-426
Author(s):  
B. Möller ◽  
S. Florentinus ◽  
F. Ganz ◽  
Y. Li ◽  
H. Kupper ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Independent Predictor ◽  
Phase Iii ◽  
Radiographic Damage ◽  
Damage Progression ◽  
Phase Iii Trials ◽  
Large Phase

Low Hemoglobin and Radiographic Damage Progression in Early Rheumatoid Arthritis: Secondary Analysis From a Phase III Trial

2018 ◽  
Vol 70 (6) ◽  
pp. 861-868 ◽  
Author(s):  
Burkhard Möller ◽  
Judith Everts-Graber ◽  
Stefan Florentinus ◽  
Yihan Li ◽  
Hartmut Kupper ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Secondary Analysis ◽  
Phase Iii ◽  
Radiographic Damage ◽  
Phase Iii Trial ◽  
Damage Progression

scholarly journals Immunotherapy Predictive Molecular Markers in Advanced Gastroesophageal Cancer: MSI and Beyond

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1715
Author(s):  
Robin Park ◽  
Laercio Lopes ◽  
Anwaar Saeed
Keyword(s):  
Treatment Options ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
Gastroesophageal Cancer ◽  
Programmed Death ◽  
Phase Iii Trials ◽  
Tumor Mutational Burden ◽  
Large Phase ◽  
Programmed Death 1

Advanced gastroesophageal cancer (GEC) has a poor prognosis and limited treatment options. Immunotherapy including the anti-programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab have been approved for use in various treatment settings in GEC. Additionally, frontline chemoimmunotherapy regimens have recently demonstrated promising efficacy in large phase III trials and have the potential to be added to the therapeutic armamentarium in the near future. There are currently several immunotherapy biomarkers that are validated for use in the clinical setting for GEC including programmed death ligand-1 (PD-L1) expression as well as the tumor agnostic biomarkers such as mismatch repair or microsatellite instability (MMR/MSI) and tumor mutational burden (TMB). However, apart from MMR/MSI, these biomarkers are imperfect because none are highly sensitive nor specific. Therefore, there is an unmet need for immunotherapy biomarker development. To this end, several biomarkers are currently being evaluated in ongoing trials with some showing promising predictive potential. Here, we summarize the landscape of immunotherapy predictive biomarkers that are currently being evaluated in GEC.

scholarly journals Golimumab for Rheumatoid Arthritis

2019 ◽  
Vol 8 (3) ◽  
pp. 387 ◽  
Author(s):  
Eleftherios Pelechas ◽  
Paraskevi Voulgari ◽  
Alexandros Drosos
Keyword(s):  
Rheumatoid Arthritis ◽  
Opportunistic Infections ◽  
Current Data ◽  
Genetically Engineered ◽  
Phase Iii ◽  
Real World Data ◽  
Standard Dosage ◽  
Subcutaneous Dose ◽  
Phase Iii Trials ◽  
Factor Α

Since the advent of infliximab for the treatment of rheumatoid arthritis (RA), new genetically-engineered molecules have appeared. This review aims to present the current data and body of evidence for golimumab (GLM). Safety, efficacy, tolerability and immunogenicity are all being investigated, not only through phase III trials (GO-BEFORE, GO-FORWARD, GO-AFTER, GO-MORE, GO-FURTHER, GO-NICE), but also through studies of real-world data. It seems that GLM in the subcutaneous form is an efficacious molecule with a good safety profile at the standard dosage scheme, but a 100 mg subcutaneous dose is associated with a higher risk of opportunistic infections, lymphoma and demyelination. Furthermore, when compared to other tumor necrosis factor-α molecules, it is non-inferior, and, at some points, such as when it comes to immunogenicity and persistence of the drug, it has a better profile. In summary, GLM is an effective, well-tolerated option for the treatment of RA, for both the clinician and patients who are seeking a convenient dosage scheme.

Intraperitoneal Chemotherapy for Ovarian Cancer: Overview and Perspective

2007 ◽  
Vol 25 (20) ◽  
pp. 2867-2872 ◽  
Author(s):  
Gautam Rao ◽  
Marta Crispens ◽  
Mace L. Rothenberg
Keyword(s):  
Ovarian Cancer ◽  
Abdominal Cavity ◽  
Drug Distribution ◽  
The United States ◽  
Phase Iii ◽  
Systemic Absorption ◽  
Current Interest ◽  
The Past ◽  
Phase Iii Trials ◽  
Large Phase

Intraperitoneal (IP) chemotherapy has theoretical, pharmacologic, and clinical advantages over intravenous (IV) chemotherapy in women with optimally debulked epithelial ovarian cancer confined to the abdominal cavity. Consistent, statistically significant improvements in both progression-free and overall survival have been demonstrated in three large phase III trials conducted in the United States during the past 10 years. Nevertheless, concerns over IP drug distribution and systemic absorption, technical challenges of IP catheter placement and the incidence of IP catheter-related complications, and the clinical relevance of these studies have limited the adoption of IP therapy in ovarian cancer. Current interest in the evaluation of molecularly targeted therapies should build on the progress that has been made through the use of IP chemotherapy in women with optimally debulked ovarian cancer.

scholarly journals Identifying the preferable rheumatoid arthritis subgroups for intervention with the anti-RANKL antibody denosumab to reduce progression of joint destruction

RMD Open ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. e001249
Author(s):  
Yoshiya Tanaka ◽  
Satoshi Soen ◽  
Naoki Ishiguro ◽  
Hisashi Yamanaka ◽  
Toshiyuki Yoneda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Nuclear Factor Κb ◽  
Phase Iii ◽  
Concomitant Treatment ◽  
Double Blind ◽  
Radiographic Damage ◽  
Interaction Factor

ObjectivesTo clarify which rheumatoid arthritis (RA) patients benefit most from the anti-receptor activator of nuclear factor-κB ligand antibody denosumab to reduce the progression of joint destruction.MethodsWe pooled patient data from the 12-month, double-blind, placebo-controlled DRIVE (phase II) and DESIRABLE (phase III) studies. In DRIVE, concomitant treatment was limited to methotrexate, salazosulfapyridine and bucillamine. In DESIRABLE, patients could receive any disease-modifying antirheumatic drug. RA patients were randomised to denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or placebo. Efficacy was assessed by van der Heijde-modified total Sharp score (mTSS), bone erosion score (ES) and joint space narrowing score (JSNS). Change in mTSS was assessed in subgroups stratified by risk factors for radiographic damage if the interaction factor was significant.ResultsThe pooled analysis included 909 patients. Denosumab reduced worsening of mTSS (mean (SD)) at 12 months in the Q6M (0.88 (3.30), p=0.0024) and Q3M (0.66 (2.16), p=0.0002) groups versus placebo (1.50 (3.73)). This reduction in mTSS progression was due to the change in ES (Q6M, 0.44 (1.89), p=0.0006; Q3M, 0.20 (0.86), p<0.0001) versus placebo (0.98 (2.54)); no effect was observed on JSNS. Anti-cyclic citrullinated peptide (CCP) antibodies, glucocorticoid use and baseline ES showed a significant interaction. Denosumab was particularly effective in patients who were anti-CCP antibody positive (p<0.05). Changes in mTSS versus placebo were observed in all denosumab dose groups, regardless of glucocorticoid use and baseline ES.ConclusionsDenosumab broadly reduced the progression of joint destruction in RA patients with risk factors for radiographic damage such as especially anti-CCP antibody positivity.

Should attribution be considered when interpreting adverse event data: A North Central Cancer Treatment Group (NCCTG) evaluation of a phase III placebo controlled trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6006-6006
Author(s):  
S. L. Hillman ◽  
S. J. Mandrekar ◽  
B. M. Bot ◽  
E. A. Perez ◽  
J. W. Kugler ◽  
...  
Keyword(s):  
Adverse Events ◽  
Controlled Trial ◽  
Phase Iii ◽  
North Central ◽  
Adverse Event Data ◽  
Phase Iii Trials ◽  
Large Phase ◽  
Multiple Cycles ◽  
Version 2.0 ◽  
Relationship Of

6006 Background: In March 1998, the Common Toxicity Criteria version 2.0 was implemented and introduced the collection and reporting of attribution of adverse events to study treatment. Collection and reporting of attribution adds time and cost to the clinical trial process, and its use while reporting adverse events (AE) in the literature has varied. We investigate whether attribution adds value to the interpretation of AE data. Methods: Patients on the placebo arm of trial 97–24–51 (CAI vs. Placebo) were chosen since the true relationship of the event to the study treatment is known (“unrelated”). Attribution was collected per CTCv2.0 and categorized as “not related” (not related or unlikely) and “related” (possible, probable, or definite). All reported AEs and the maximum severity for a given AE were evaluated. Patterns were evaluated using generalized estimating equations adjusting for multiple events per patient. Changes in attribution over time for the same event were computed. Results: 84 patients on the placebo arm experienced a total of 1013 AEs. 47% of AEs were reported as “related” with 36% reported as possibly related. Known CAI AEs were more likely to be reported as “related” (p = 0.005). Pulmonary AEs were more likely to be reported as “not related” (p = 0.0006). No patterns were observed by gender, age, PS, severity or treatment cycle of AE. When the same event was reported on the same patient in multiple cycles, the attribution category changed at least once 36% of the time with 25% changing from “related” to “unrelated” or vice versa. Conclusion: Almost 50% of events on a placebo arm of a phase III trial were reported as being attributed to study treatment and 25% of the time the same event was not consistently attributed. These data suggest that attribution is difficult to determine, unreliable, and thus its value in large phase III trials is questionable. [Table: see text] No significant financial relationships to disclose.

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