Dataset Information

Exploitation of Precision Medicine Trials Data: Examples of Long Responders From the SHIVA01 Trial.

ABSTRACT: Purpose:Precision medicine trials constitute a precious source of molecular data with prospective clinical annotations allowing the exploration of patients' subpopulations according to specific clinical or biological questions. Using the SHIVA01-the first randomized trial comparing molecularly targeted therapy on the basis of tumor molecular profiling versus conventional chemotherapy in metastatic cancer patients who failed standard of care therapy-annotated database, we report cases of patients treated in the trial with targeted therapy who experienced an objective response or prolonged disease stabilization in light of patients' molecular alterations. Patients and Methods:We selected all patients included in SHIVA01 treated with a molecularly targeted agent (MTA) who experienced an objective response or disease stabilization that lasted longer than 6 months according to Response Evaluation Criteria in Solid Tumors version 1.1. Results:Among the 170 patients who received MTAs in the SHIVA01 trial, 15 patients (9%) experienced an objective response (n = 3) or disease stabilization that lasted longer than 6 months (n = 12). The most frequent histologic subtypes were breast cancer (27%) and cervical cancer (20%). Six patients, including three patients with breast cancer, were treated with abiraterone on the basis of androgen receptor protein overexpression. Five patients were treated with everolimus on the basis of a PTEN heterozygous deletion with loss of protein expression, PIK3CA mutation, or both alterations. The remaining four patients were treated with tamoxifen, erlotinib, imatinib, and vemurafenib on the basis of progesterone receptor expression, EGFR amplification, KIT mutation, and BRAF mutation, respectively. TP53 mutations were absent in responder patients. Conclusion:Analysis of patients who experienced objective responses or disease stabilization that lasted longer than 6 months allowed the identification of potential biomarkers of sensitivity and resistance to MTAs.

SUBMITTER: Basse C

PROVIDER: S-EPMC7450915 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exploitation of Precision Medicine Trials Data: Examples of Long Responders From the SHIVA01 Trial.

Basse Clémence C Morel Claire C Callens Céline C Pierron Gaëlle G Servois Vincent V Vincent-Salomon Anne A Jobard Aude A Alt Marie M Ricci Francesco F Loirat Delphine D Sablin Marie-Paule MP Bretagne Marie M Saint-Ghislain Mathilde M Hescot Ségolène S Gonçalves Anthony A Tredan Olivier O Dubot Coraline C Gavoille Céline C Delord Jean-Pierre JP Campone Mario M Isambert Nicolas N Belin Lisa L Bieche Ivan I Kamal Maud M Le Tourneau Christophe C

JCO precision oncology 20181019

<h4>Purpose</h4>Precision medicine trials constitute a precious source of molecular data with prospective clinical annotations allowing the exploration of patients' subpopulations according to specific clinical or biological questions. Using the SHIVA01-the first randomized trial comparing molecularly targeted therapy on the basis of tumor molecular profiling versus conventional chemotherapy in metastatic cancer patients who failed standard of care therapy-annotated database, we report cases of ...[more]

PMID: 32914004

Similar Datasets

Project description:ObjectiveThe classical description of Dravet syndrome, the prototypic developmental and epileptic encephalopathy, is of a normal 6-month-old infant presenting with a prolonged, febrile, hemiclonic seizure and showing developmental slowing after age 1 year. SCN1A pathogenic variants are found in >80% of patients. Many patients have atypical features resulting in diagnostic delay and inappropriate therapy. We aimed to provide an evidence-based definition of SCN1A-Dravet syndrome in readiness for precision medicine trials.MethodsEpilepsy patients were recruited to the University of Melbourne Epilepsy Genetics Research Program between 1995 and 2020 by neurologists from around the world. Patients with SCN1A pathogenic variants were reviewed and only those with Dravet syndrome were included. Clinical data, including seizure and developmental course, were analyzed in all patients with SCN1A-Dravet syndrome.ResultsTwo hundred and five patients were studied at a median age of 8.5 years (range 10 months to 60 years); 25 were deceased. The median seizure-onset age was 5.7 months (range 1.5-20.6 months). Initial seizures were tonic-clonic (52%) and hemiclonic (35%), with only 55% being associated with fever. Only 34% of patients presented with status epilepticus (seizure lasting ≥30 minutes). Median time between first and second seizure was 30 days (range 4 hours to 8 months), and seven patients (5%) had at least 6 months between initial seizures. Median ages at onset of second and third seizure types were 9.1 months (range 3 months-25.4 years) and 15.5 months (range 4 months-8.2 years), respectively. Developmental slowing occurred prior to 12 months in 27%.SignificanceAn evidence-based definition of SCN1A-Dravet syndrome is essential for early diagnosis. We refine the spectrum of Dravet syndrome, based on patterns of seizure onset, type, and progression. Understanding of the full spectrum of SCN1A-Dravet syndrome presentation is essential for early diagnosis and optimization of treatment, especially as precision medicine trials become available.

Dataset Information

Exploitation of Precision Medicine Trials Data: Examples of Long Responders From the SHIVA01 Trial.

Publications

Exploitation of Precision Medicine Trials Data: Examples of Long Responders From the SHIVA01 Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets