Black Disparities in Targeted Therapy Clinical Trials – A Call for Future Reset

Studies show marked disparities in the relative risk of cancer death between Black Americans and White Americans even after adjusting for the stage at diagnosis and age. This may be explained by disparities in different aspects of cancer care including providing equal screening opportunities, availability of proper treatment options and inclusivity in clinical trials. To our knowledge, our study is the first descriptive study on Black disparities in targeted therapy clinical trials. We collected data on Black inclusivity from pivotal clinical trials as well as trials of special interest involving targeted therapies in some of the commonly encountered cancers. Our results show that most targeted therapy trials included in our review were multinational including some participating countries with very few or no Blacks and therefore had very poor Black representation with an average of around 1-3%. Also, some trials lacked transparent data on the racial demographics raising concerns on the generalizability of data when extrapolated to treat the Black population. We have reviewed existing literature on differences in cancer biology and host biology depending on the race and end with suggestions to improve Black inclusivity in clinical trials.

Download Full-text

Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

Pharmaceuticals ◽

10.3390/ph14010051 ◽

2021 ◽

Vol 14 (1) ◽

pp. 51

Author(s):

Brinda Balasubramanian ◽

Simran Venkatraman ◽

Kyaw Zwar Myint ◽

Tavan Janvilisri ◽

Kanokpan Wongprasert ◽

...

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Drug Development ◽

Surgical Resection ◽

Treatment Options ◽

Standard Of Care ◽

Time Data ◽

Current Standard ◽

Innovative Drug ◽

Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

Download Full-text

Is there a role for adjuvant therapy after surgery in “high risk for recurrence” kidney cancer? An update on current concepts

Current Oncology ◽

10.3747/co.25.3865 ◽

2018 ◽

Vol 25 (5) ◽

Cited By ~ 3

Author(s):

T. Sharma ◽

C. Tajzler ◽

A. Kapoor

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

High Risk ◽

Adjuvant Therapy ◽

Patient Population ◽

Treatment Options ◽

Significant Proportion ◽

High Risk Patient ◽

Disease Free Survival ◽

Cochrane Reviews

BackgroundAlthough surgical resection remains the standard of care for localized kidney cancers, a significant proportion of patients experience systemic recurrence after surgery and hence might benefit from effective adjuvant therapy. So far, several treatment options have been evaluated in adjuvant clinical trials, but only a few have provided promising results. Nevertheless, with the recent development of targeted therapy and immunomodulatory therapy, a series of clinical trials are in progress to evaluate the potential of those novel agents in the adjuvant setting. In this paper, we provide a narrative review of the progress in this field, and we summarize the results from recent adjuvant trials that have been completed.MethodsA literature search was conducted. The primary search strategy at the medline, Cochrane reviews, and http://ClinicalTrials.gov/ databases included the keywords “adjuvant therapy,” “renal cell carcinoma,” and “targeted therapy or/and immunotherapy.”ConclusionsData from the s-trac study indicated that, in the “highest risk for recurrence” patient population, disease-free survival was increased with the use of adjuvant sunitinib compared with placebo. The assure trial showed no benefit for adjuvant sunitinib or sorafenib in the “intermediate- to high-risk” patient population. The ariser (adjuvant girentuximab) and protect (adjuvant pazopanib) trials indicated no survival benefit, but subgroup analyses in both trials recommended further investigation. The inconsistency in some of the current results can be attributed to a variety of factors pertaining to the lack of standardization across the trials. Nevertheless, patients in the “high risk of recurrence” category after surgery for their disease would benefit from a discussion about the potential benefits of adjuvant treatment and enrolment in ongoing adjuvant trials.

Download Full-text

Systemic treatment options for advanced biliary tract carcinoma

Journal of Gastroenterology ◽

10.1007/s00535-020-01712-9 ◽

2020 ◽

Vol 55 (10) ◽

pp. 944-957

Author(s):

Changqing Xie ◽

Nicole A. McGrath ◽

Cecilia Monge Bonilla ◽

Jianyang Fu

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Biliary Tract ◽

Treatment Options ◽

Single Agent ◽

Current Status ◽

Dna Mismatch ◽

First Line Therapy ◽

Molecular Landscape ◽

Line Setting

Abstract Advanced biliary tract cancers (BTC) include a diverse collection of rare and heterogenous tumors with poor prognosis. The combination of gemcitabine and cisplatin is the established first-line therapy for advanced BTC. There are no accepted standard treatments in the second line setting, though there are several ongoing clinical trials that implement chemotherapy as a therapeutic strategy. The understanding of the molecular landscape of BTC has offered hope of targeted therapies to the identified actionable genomic aberrations, such as FGFR2 gene fusions, mutations of IDH1/2, HER2, BRAC1/2 and BRAF. Pembigatinib has become the first approved targeted therapy for BTC with FGFR2 fusion or other rearrangements. Recent immunotherapy has opened new therapy avenues in BTC with pembrolizumab approved for either microsatellite instability high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors, including BTC. The combination of immunotherapy with other modalities is currently being evaluated in different clinical trials, since single agent immunotherapy appears to provide modest benefits in advanced BTC. In this review, we summarize the current status of treatment options, including systemic chemotherapy, targeted therapy, immunotherapy, and various combinations in advanced BTC.

Download Full-text

New Treatment Options for Advanced Gastroesophageal Tumours: Mature for the Current Practice?

Cancers ◽

10.3390/cancers12020301 ◽

2020 ◽

Vol 12 (2) ◽

pp. 301

Author(s):

Hannah Christina Puhr ◽

Matthias Preusser ◽

Gerald Prager ◽

Aysegül Ilhan-Mutlu

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Targeted Therapies ◽

Current Practice ◽

Treatment Options ◽

Novel Agents ◽

Novel Treatment ◽

New Treatment ◽

Current Impact

Several clinical trials attempted to identify novel treatment options for advanced gastroesophageal tumours in first, second and further lines. Although results of targeted therapy regimens were mainly disappointing, novel immunotherapy agents showed promising activity, which led to their approval in second and third lines in many countries. This review focuses on the results of recent clinical trials investigating novel agents including targeted therapies, immunotherapy components and chemotherapies and discuss their current impact as well as current approval status on the treatment armamentarium of advanced gastroesophageal tumours.

Download Full-text

Progression-Free Survival as a Surrogate for Overall Survival in Clinical Trials of Targeted Therapy in Advanced Solid Tumors

Drugs ◽

10.1007/s40265-017-0728-y ◽

2017 ◽

Vol 77 (7) ◽

pp. 713-719 ◽

Cited By ~ 14

Author(s):

Stefan Michiels ◽

Everardo D. Saad ◽

Marc Buyse

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Targeted Therapy ◽

Solid Tumors ◽

Progression Free Survival ◽

Advanced Solid Tumors ◽

Free Survival

Download Full-text

Therapeutic clinical trials to combat COVID-19 pandemic in India: analysis from trial registry

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0208 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Angelika Batta ◽

Raj Khirasaria ◽

Vinod Kapoor ◽

Deepansh Varshney

Keyword(s):

Clinical Trials ◽

De Novo ◽

Treatment Options ◽

Drug Repurposing ◽

Trial Registry ◽

Therapeutic Treatment ◽

Clinical Trial Registry ◽

Clear Cut ◽

Therapeutic Trials ◽

Microsoft Office

AbstractObjectivesWith the emergence of Novel corona virus, hunt for finding a preventive and therapeutic treatment options has already begun at a rapid pace with faster clinical development programs. The present study was carried out to give an insight of therapeutic interventional trials registered under clinical trial registry of India (CTRI) for COVID-19 pandemic.MethodsAll trials registered under CTRI were evaluated using keyword “COVID” from its inception till 9th June 2020. Out of which, therapeutic interventional studies were chosen for further analysis. Following information was collected for each trial: type of therapeutic intervention (preventive/therapeutic), treatment given, no. of centers (single center/multicentric), type of institution (government/private), study design (randomized/single-blinded/double-blinded) and sponsors (Government/private). Microsoft Office Excel 2007 was used for tabulation and analysis.ResultsThe search yielded total of 205 trials, out of which, 127 (62%) trials were interventional trials. Out of these, 71 (56%) were AYUSH interventions, 36 (28.3%) tested drugs, 9 (7%) tested a nondrug intervention, rest were nutraceuticals and vaccines. About 66 (56%) were therapeutic trials. Majority were single-centered trials, i.e. 87 (73.7%). Trials were government funded in 57 (48.3%) studies. Majority were randomized controlled trials, i.e. 67 (56.8%). AYUSH preparations included AYUSH-64, Arsenic Album, SamshamaniVati etc.ConclusionsThe number of therapeutic interventional clinical trials was fair in India. A clear-cut need exists for an increase in both quantity and quality of clinical trials for COVID-19. Drug repurposing approach in all systems of medicine can facilitate prompt clinical decisions at lower costs than de novo drug development.

Download Full-text

Variation in treatment preferences of pulmonary exacerbations among Australian and New Zealand cystic fibrosis physicians

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2021-000956 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000956

Author(s):

Grace Currie ◽

Anna Tai ◽

Tom Snelling ◽

André Schultz

Keyword(s):

Cystic Fibrosis ◽

Clinical Trials ◽

New Zealand ◽

Treatment Options ◽

Early Response ◽

Treatment Preferences ◽

Dornase Alfa ◽

Clinical Scenarios ◽

Professional Opinion ◽

Pulmonary Exacerbations

BackgroundDespite advances in cystic fibrosis (CF) management and survival, the optimal treatment of pulmonary exacerbations remains unclear. Understanding the variability in treatment approaches among physicians might help prioritise clinical uncertainties to address through clinical trials.MethodsPhysicians from Australia and New Zealand who care for people with CF were invited to participate in a web survey of treatment preferences for CF pulmonary exacerbations. Six typical clinical scenarios were presented; three to paediatric and another three to adult physicians. For each scenario, physicians were asked to choose treatment options and provide reasons for their choices.ResultsForty-nine CF physicians (31 paediatric and 18 adult medicine) participated; more than half reported 10+ years of experience. There was considerable variation in primary antibiotic selection; none was preferred by more than half of respondents in any scenario. For secondary antibiotic therapy, respondents consistently preferred intravenous tobramycin and a third antibiotic was rarely prescribed, except in one scenario describing an adult patient. Hypertonic saline nebulisation and twice daily chest physiotherapy was preferred in most scenarios while dornase alfa use was more variable. Most CF physicians (>80%) preferred to change therapy if there was no early response. Professional opinion was the most common reason for antibiotic choice.ConclusionsVariation exists among CF physicians in their preferred choice of primary antibiotic and use of dornase alfa. These preferences are driven by professional opinion, possibly reflecting a lack of evidence to base policy recommendations. Evidence from high-quality clinical trials is needed to inform physician decision making.

Download Full-text

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Journal of Clinical Medicine ◽

10.3390/jcm10040711 ◽

2021 ◽

Vol 10 (4) ◽

pp. 711

Author(s):

Byung-Chul Lee ◽

Insung Kang ◽

Kyung-Rok Yu

Keyword(s):

Clinical Trials ◽

Therapeutic Agent ◽

Therapeutic Potential ◽

Therapeutic Option ◽

Treatment Options ◽

Genetic Material ◽

Experimental Models ◽

Attractive Alternative ◽

Cell Based Therapy ◽

Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

Download Full-text

Dystrophinopathies and Limb-Girdle Muscular Dystrophies

Neuropediatrics ◽

10.1055/s-0037-1601860 ◽

2017 ◽

Vol 48 (04) ◽

pp. 262-272 ◽

Cited By ~ 9

Author(s):

Anna Sarkozy ◽

Mariacristina Scoto ◽

Francesco Muntoni ◽

Joana Domingos

Keyword(s):

Clinical Trials ◽

Treatment Options ◽

Shoulder Girdle ◽

Muscle Disease ◽

Standards Of Care ◽

Muscular Dystrophies ◽

New Treatment ◽

Shoulder Girdle Muscles ◽

Independent Ambulation ◽

Duchenne's Muscular Dystrophy

AbstractMuscular dystrophies are a heterogeneous group of inherited diseases. The natural history of these disorders along with their management have changed mainly due to a better understanding of their pathophysiology, the evolution of standards of care, and new treatment options. Dystrophinopathies include both Duchenne's and Becker's muscular dystrophies, but in reality they are a spectrum of muscle diseases caused by mutations in the gene that encodes the protein dystrophin. Duchenne's muscular dystrophy is the most common form of inherited muscle disease of childhood. The current standards of care considerably prolong independent ambulation and survival. Several therapeutic options either aiming at substituting/correcting the primary protein defect or limiting the progression of the dystrophic process are currently being explored in clinical trials.Limb-girdle muscular dystrophies (LGMDs) are rare and heterogeneous conditions, characterized by weakness and wasting of the pelvic and shoulder girdle muscles. Originally classified into dominant and recessive, > 30 genetic forms of LGMDs are currently recognized. Further understanding of the pathogenic mechanisms of LGMD will help identifying novel therapeutic approaches that can be tested in clinical trials.

Download Full-text