Chemotherapy and Targeted Therapy in Advanced Biliary Tract Carcinoma: A Pooled Analysis of Clinical Trials

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.

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Systemic Treatment of Advanced Biliary Tract Carcinoma: Emerging Roles of Targeted Therapy and Molecular Profiling

Clinical Cancer Drugs ◽

10.2174/2212697x02666151020212855 ◽

2015 ◽

Vol 2 (2) ◽

pp. 80-86 ◽

Cited By ~ 4

Author(s):

Edward Wyluda ◽

Nelson Yee

Keyword(s):

Targeted Therapy ◽

Biliary Tract ◽

Systemic Treatment ◽

Molecular Profiling ◽

Biliary Tract Carcinoma

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Impact of geographic region on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4583 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4583-4583

Author(s):

Andre Poisl Fay ◽

Rana R. McKay ◽

Xun Lin ◽

Ronit Simantov ◽

Toni K. Choueiri

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Survival Data ◽

Western Europe ◽

Univariate Analysis ◽

Patient Characteristics ◽

Pooled Analysis ◽

Geographic Region ◽

Health Determinants ◽

Rank Test

4583 Background: Health determinants vary according to the geographic region and may impact the outcomes of mRCC patients treated on clinical trials of targeted therapy. We investigate the OS by geographic region of mRCC patients treated in the targeted therapy era. Methods: We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Clinical characteristics and survival data were collected. Statistical analyses were performed using the Kaplan-Meier method and log-rank test in univariate analysis. Results: Overall, 4736 patients were included in the analysis. Patient characteristics differed according to geographic region (table). No statistically significant differences in OS were observed when comparing US/Canada (USC, reference) to other regions: Latin America (LA), Asia/Oceania/Africa (AOA), and Eastern Europe (EE). OS differed among patients enrolled on trials in the USC compared to Western Europe (WE) (20.3 vs.17.4 months, respectively; HR: 1.15; 95%CI 1.03-1.3 p = 0.015). All grade treatment-related adverse events (AE) were reported more frequently in USC. There were no significant differences in grade 3-5 AEs between groups. Conclusions: We highlight that despite differing baseline characteristics, OS was similar among most geographic regions. Factors such as disease biology, access to care, AE reporting, and quality of care that may contribute to potential differences in outcomes among regions need to be further characterized. [Table: see text]

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