Abstract
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.
Highlights
We propose that the implementation of co-clinical trials will expedite the approval of targeted therapy drugs in CCA by improving trial outcomes
It is noteworthy that the FDA granted accelerated approval for pemigatinib, a novel FGFR inhibitor, to be used in treatment of CCA patients that are positive for FGFR2 fusions and have failed first line chemotherapy [36] based on outcomes from a multi-cohort Phase II clinical trial [NCT04096417]
In co-clinical trials, the candidate drugs are tested in preclinical animal models, that represent the genetic subtypes of patients, using the same protocol that is to be used in the clinical trials
Summary
Known as “precision oncology”, considers the heterogeneity of cancer and abandoning the “one size fits all” premise It combines different aspects of molecular profiling to appropriately inform diagnosis, prognosis, and thereby customizing treatment for patients, individually [19]. This is practiced in high-income countries (HICs) for prevalent cancers such those of the lung, breast, etc., to predict treatment outcomes in patients [20]. A majority of clinical trials with targeted therapy drugs fail to meet their endpoint objectives, mainly because a mixed cohort of patients are recruited to the study, as a consequence, the test drugs result in poor outcomes and fail to get regulatory approval [27]. Improved outcomes from clinical trials will encourage the approval of targeted therapy drugs for the selected cohort of CCA patients
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