scholarly journals Systemic treatment options for advanced biliary tract carcinoma

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.

scholarly journals Use of first-line trabectedin in advanced leiomyosarcoma: a review of clinical data and future perspectives

2016 ◽  
Vol 4 (1) ◽  
pp. 6-10
Author(s):  
Nadia Hindi ◽  
Florence Duffaud ◽  
Giacomo Giulio Baldi ◽  
Patricia Pautier
Keyword(s):  
Clinical Trials ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Large Subgroup ◽  
Myxoid Liposarcomas ◽  
Line Setting

Leiomyosarcomas (LMS) represent a large subgroup of soft-tissue sarcoma (STS) generally considered moderately sensitive to conventional chemotherapy. Single-agent doxorubicin is the standard first-line therapy for advanced non-selected STS, although combination with ifosfamide appears to be superior in terms of objective response. Gemcitabine-based regimes, dacarbazine, trabectedin and pazopanib seem to be especially active in patients with advanced LMS, while the activity of ifosfamide in this histotype is low. Data derived from clinical trials and retrospective series show that trabectedin is especially active in L-sarcomas including non-gynecological and uterine LMS as well as liposarcomas, in particular myxoid liposarcomas. Trabectedin has also been tested in the first-line setting, alone or in combination with doxorubicin, for the treatment of LMS of uterine and non-uterine origin in a trial by the French Sarcoma Group (phase II study LMS-02) with encouraging results in terms of median progression-free survival and objective response. The toxicity profile of trabectedin appears to be comparable to, or even more manageable than, that of other chemotherapy combinations in the first-line setting. Designing new clinical trials based on specific histologic subtypes is feasible, and the results of such studies would help to optimize the management of patients with STS.

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

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.

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

2018 ◽  
Vol 25 (5) ◽  
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.

scholarly journals Current approaches to the management of diabetic retinopathy

2014 ◽  
Vol 17 (3) ◽  
pp. 122-128 ◽  
Author(s):  
Tatiana Yul'evna Demidova ◽  
Yulia Alexandrovna Trakhtenberg
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Diabetic Retinopathy ◽  
Mechanism Of Action ◽  
Treatment Options ◽  
Current Status ◽  
Antiangiogenic Agents

This review reflects the current status of the diabetic retinopathy treatment problem and describes the results of the largest trials on epidemiology, screening and the risk factors for complications. In addition, this article describes the current approaches and treatment options for diabetic retinopathy, including a description of fenofibroic acid with its mechanism of action and data from clinical trials. This article also contains information on antiangiogenic agents for intravitreal administration.

The treatment of advanced stage favorable histology non-Hodgkin's lymphoma: a preliminary report of a randomized trial comparing single agent chemotherapy, combination chemotherapy, and whole body irradiation

Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 592-598 ◽  
Author(s):  
RT Hoppe ◽  
P Kushlan ◽  
HS Kaplan ◽  
SA Rosenberg ◽  
BW Brown
Keyword(s):  
Clinical Trials ◽  
Combination Chemotherapy ◽  
Treatment Options ◽  
Single Agent ◽  
Treatment Protocol ◽  
Whole Body ◽  
Remission Induction ◽  
Advanced Stage ◽  
Favorable Histology ◽  
Hodgkin's Lymphomas

Abstract Between 1975 and 1978, 51 patients with favorable histology non- Hodgkin's lymphomas, pathologic stage III-IV, were treated prospectively on a randomized treatment protocol. Treatment options were single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP), or fractionated whole body irradiation followed by low dose involved field irradiation. The median follow-up interval in this group of patients is not 41 mo. Actuarial survival is excellent, 84% at 4 yr for the entire group, with similar survival observed for each of the three treatment options. Initial complete remission rates (64%, 88%, and 71%) were not significantly different in the three treatment arms. Frequent relapse after initial remission induction was noted, however, with a freedom from relapse at 4 yr of only 25%. The toxicities of the three therapies were acceptable. Acute complications of therapy were most numerous in the group of patients treated with CVP; however, long-term hematologic depression was most commonly observed in patients treated with whole body irradiation. In general, hematologic complications were more frequent among patients who had marrow involvement and intact spleens at the time of initial therapy. The relationship of this study to other clinical trials in the management of patients with advanced stage favorable histology lymphomas and its implications for future clinical trials are discussed.

scholarly journals Contemporary Tailored Oncology Treatment of Biliary Tract Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Fiona Turkes ◽  
Juliet Carmichael ◽  
David Cunningham ◽  
Naureen Starling
Keyword(s):  
Clinical Trials ◽  
Biliary Tract ◽  
Treatment Options ◽  
Prognostic Significance ◽  
Response To Treatment ◽  
Genomic Profiling ◽  
Biliary Tract Cancers ◽  
Comprehensive Genomic Profiling ◽  
Genomic Aberrations ◽  
Oncology Treatment

Biliary tract cancers (BTCs) are poor prognosis malignancies with limited treatment options. Capecitabine has recently emerged as an effective agent in the adjuvant setting; however, treatment of advanced disease is still limited to first-line cisplatin and gemcitabine chemotherapy. Recent global efforts in genomic profiling and molecular subtyping of BTCs have uncovered a wealth of genomic aberrations which may carry prognostic significance and/or predict response to treatment, and several targeted agents have shown promising results in clinical trials. As such, the uptake of comprehensive genomic profiling for patients with BTCs and the expansion of basket trials to include these patients are growing. This review describes the currently approved systemic therapies for BTCs and provides insight into the emerging targeted and immunotherapeutic agents, as well as conventional chemotherapeutic regimes, currently being investigated in clinical trials.

Relapsed Multiple Myeloma

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 303-309 ◽  
Author(s):  
Sagar Lonial
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Phase 1 ◽  
Treatment Options ◽  
Single Agent ◽  
Great Promise ◽  
New Agents ◽  
Ongoing Work ◽  
The Many

Abstract Advances in treatment options for patients with multiple myeloma have made a significant impact on the overall survival of patients and have helped achieve levels of response and duration of remission previously not achievable with standard chemotherapy-based approaches. These improvements are due, in large part, to the development of the novel agents thalidomide, bortezomib, and lenalidomide, each of which has substantial single-agent activity. In addition, a large number of second-generation agents are also in clinical development, such that the repertoire of available treatment options continues to expand. To better interpret clinical trials performed in the relapsed setting, it is important that definitions of relapse categories are used to help better pinpoint the specific benefit for a given therapy, especially in the combination therapy setting as it aids in determining if ongoing work should be continued or abandoned for a given new agent. Insights from preclinical modeling and in vitro work have identified several new combinations, new targets and second- or third-generation versions of existing targets that hold great promise in the setting of relapsed myeloma. Combinations of thalidomide, bortezomib, and lenalidomide with conventional agents or among each other have resulted in enhanced response rates and efficacy. Clinical trials of agents such as carfilzomib, pomalidomide, vorinostat, panobinostat, and elotuzomab are just a few of the many exciting new compounds that are being tested in phase 1 and phase 2 clinical trials for relapsed patients. Further clinical and translational testing are critical to better understanding how best to combine these new agents, as well as identifying patient populations that may best benefit from treatment with these developing new agents.

scholarly journals NTRK2 Fusion Driven Pediatric Glioblastoma: Identification of key molecular drivers by personalized oncology

2019 ◽  
Vol 46 (s2) ◽  
pp. S64
Author(s):  
Levine ◽  
Y Shen ◽  
K Mungall ◽  
J Serrano ◽  
M Snuderl ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Braf V600e ◽  
Current Status ◽  
Driver Mutations ◽  
List Type ◽  
Idh1 R132h ◽  
Tyrosine Kinase 2 ◽  
Cerebellar Glioblastoma ◽  
Molecular Landscape

We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Explore the current molecular landscape of pediatric high grade gliomas2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors3.Discuss the current status of NTRK inhibitor clinical trials

Resistance to BRAF inhibition in melanoma: An epigenetic approach.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19040-e19040 ◽  
Author(s):  
Steve Walston ◽  
Nicolaus Gordon ◽  
Arnab Chakravarti ◽  
Kamalakannan Palanichamy
Keyword(s):  
Targeted Therapy ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Single Agent ◽  
Annexin V ◽  
Invasive Disease ◽  
Braf V600e ◽  
Cancer Genes ◽  
Braf Inhibition

e19040 Background: Melanoma only accounts for 4% of skin cancer while causing 75% of cancer related deaths. Worldwide incidence is increasing faster than any other cancer, and there are few effective treatment options for invasive disease translating to poor survival. The burgeoning understanding of molecular mechanisms driving carcinogenesis creates unique opportunities to develop targeted therapy. This is especially apparent in the case of BRAF in melanoma. BRAF V600E mutations occur in up to 50% of melanomas endowing these tumors with a constitutively activated MAPK pathway. Blockade of BRAF mutated tumors shows impressive initial responses above 80%. However, single-agent targeted therapy is often plagued with an emergence of resistant clones, and these impressive responses were transient. Diverse resistance mechanisms have been reported at the transcriptome level in patients treated with BRAF inhibitors. However, reports elucidating the prominent epigenetic regulators of resistance to BRAF inhibition are lacking. Methods: We sequenced the DNA of 14 melanoma cell lines and determined 9 had BRAF V600E mutation and 5 were wild type. We also sequenced cancer genes such as p53, PTEN, cKit, NRAS, etc. The BRAF mutant cells were exposed to PLX4032 (BRAF V600E inhibitor) and the concentrations were incrementally increased to develop resistant clones. This resistance was corroborated using annexin V / PI assay to display approximately a 50% decrease in apoptosis in drug resistant cells compared with control cells after 5 days of 5 µM PLX4032 exposure. The epigenome was profiled in control and resistance clones. Results: The statistically significant clusters were identified and currently we are validating their relevance using functional models. We are also profiling the epigene expression levels in melanoma patient biopsies to determine their predictive and prognostic value. Conclusions: It is likely the epigenome plays an integral role in the previously demonstrated mechanisms of BRAF resistance. Our study should illuminate connections with pathways conveying drug resistance to increase understanding of these mechanisms. Consequently, it may be possible to develop improved treatments and prognostic biomarkers.

Analysis of real-world data (RWD) on treatment (tx) sequencing in patients with advanced non-small cell lung cancer (aNSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20642-e20642
Author(s):  
Meng Ma ◽  
Xiang Zhou ◽  
Howard Goldsweig ◽  
Nicholas Hahner ◽  
Dianwei Han ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Rank Test ◽  
Real World Data ◽  
Therapeutic Modalities ◽  
Platinum Based Chemotherapy ◽  
Line Of Therapy ◽  
Line Setting

e20642 Background: While optimal sequencing of systemic therapy in aNSCLC is critical to achieve maximal clinical benefit, it is practically challenging to study tx sequencing through clinical trials. RWD allow retrospective, observational studies to examine tx patterns and associated clinical outcomes. Methods: 1,609 aNSCLC patients who received systemic therapies at Mount Sinai hospitals were analyzed for the number of line of therapy (LOT), therapeutic modalities (chemotherapy, targeted therapy and immunotherapy), and the sequence in which treatments were given when LOT > 1. Time to tx discontinuation (TTD) was used as a surrogate clinical endpoint for outcomes. Results: 578 of the 1,609 (36%) patients received more than one LOT. 356 (22%) received tyrosine kinase inhibitors (TKIs), and 297 (16%) received immune checkpoint inhibitors (CPIs). Kaplan-Meier analysis revealed that among 297 patients who received CPIs, median TTD was longer in the 1st line setting (295 days, 95% CI 169 to 523; n=132) than when LOT > 1 (169 days, 95% CI 113 to 269; n=165), although the difference was not statistically significant (P=0.092, log-rank test). No difference of TTD on TKIs was observed between LOT = 1 and LOT > 1 (P=0.51). With respect to tx sequencing, when patients (n=94) received TKIs as the 1st LOT, 60%, 35%, and 5% of them received another TKI, chemotherapy, or a CPI-containing regimen, respectively, as the 2nd LOT. Among patients (n=370) who progressed on 1st line platinum-based chemotherapy, 52%, 32%, and 16% received another chemo regimen, a CPI-containing regimen, or a targeted therapy, respectively, as the 2nd LOT; these percentages shifted significantly toward more CPIs (24%, 66%, 10% for chemo, CPI, targeted, respectively) when only 2016-2018 data were examined. In the 2nd line setting after platinum therapy, TTD was significantly longer in the CPI group (332 days, 95% CI 169-484) compared to the chemo group (88 days, 95% CI 65-100; P<0.0001), consistent with results from pivotal clinical trials. Conclusions: As the tx algorithm of aNSCLC has been evolving rapidly, we observed diverse tx patterns in RWD. Various tx sequences may impact patient outcomes, and therefore warrant further investigation.

Sign in / Sign up

Export Citation Format

Share Document