Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial

Subbiah, Vivek; Lassen, Ulrik; Élez, Elena; Italiano, Antoîne; Curigliano, Giuseppe; Javle, Milind; Braud, Filippo de; Prager, Gerald W.; Greil, Richard; Stein, Alexander; Fasolo, Angelica; Schellens, Jan H.M.; Wen, Patrick Y.; Viele, Kert; Boran, Aislyn; Gasal, Eduard; Burgess, Paul; Ilankumaran, Palanichamy; Wainberg, Zev A.

doi:10.1016/s1470-2045(20)30321-1

Cited by 373 publications

(261 citation statements)

References 33 publications

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“…However, the PFS primary end point was improved compared to placebo (2.7 vs. 1.4 months; HR 0.37; p < .0001) (Table 4). 48 Numerous other potential targetable genes and molecular pathways are currently being studied in ongoing clinical trials 49 . With better understanding of the cancer molecular profiles, this may open a window into the biology of individual tumors and allow prediction of treatment response 50 …”

Section: The Role Of Targeted Therapy In Ccamentioning

confidence: 99%

Outcomes of neoadjuvant therapy for cholangiocarcinoma: A review of existing evidence assessing treatment response and R0 resection rate

O’Connor

et al. 2020

Journal of Surgical Oncology

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Adjuvant chemotherapy for cholangiocarcinoma (CCA) has not been shown to gain significant improvements in survival. Factors contributing to suboptimal treatment response include aggressive disease biology and late clinical presentation. When feasible, surgical resection is the first line of treatment. Yet, recurrence remains high and longterm survival is rare. Neoadjuvant therapy is an appealing approach, with oncologic advantages in allowing the treatment of occult systemic disease and selection of patients most likely to benefit from radical surgery. However, given the surgery-first treatment paradigm for CCA, there is a paucity of data supporting neoadjuvant therapy. This review summarizes the current evidence on treatment response and margin-negative (R0) resection rate associated with neoadjuvant therapy for CCA.

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Section: The Role Of Targeted Therapy In Ccamentioning

confidence: 99%

Outcomes of neoadjuvant therapy for cholangiocarcinoma: A review of existing evidence assessing treatment response and R0 resection rate

O’Connor

et al. 2020

Journal of Surgical Oncology

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“…The final report among the 43 patients with refractory BTC showed an investigator-assessed ORR of 51%, a median PFS and median OS of nine months and 14 months, respectively. The results indicated that D + T have promising efficacy in patients with ABTC, as well as favorable safety profile [ 89 ].…”

Section: Raf/mekmentioning

confidence: 99%

Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials

et al. 2021

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Biliary tract cancer (BTC) compromises a heterogenous group of tumors with poor prognoses. Curative surgery remains the first choice for localized disease; however, most BTC patients have had unresectable or metastatic disease. The gold standard therapy for these patients is chemotherapy with gemcitabine and cisplatin. There are no consensus guidelines for standard treatment in a second-line setting, although the data of the ABC-06 trial showed a slight survival benefit from oxaliplatin and 5-fluorouracil combination chemotherapy. Recent progress in comprehensive genomic profiling for advanced BTC (ABTC) has helped to clarify tumorigenesis and facilitate the coming era of precision medicine. Generally, targeted agents fail to show significant clinical benefits in unselected populations. Only fibroblast growth factor receptor 2 (FGFR2) fusion and isocitrate dehydrogenase (IDH)- and BRAF mutation-enriched populations have survival benefits from the corresponding inhibitors. Several interesting targeted agents for monotherapies or combination therapies with other compounds are currently ongoing or recruiting. Here, we review the published data from clinical trials of second-line therapies after the failure of gemcitabine-based chemotherapy in ABTC. The results were stratified by different genetic alternations, as well as by chemotherapy, targeted therapy and immunotherapy.

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“…Subbiah et al reported the effect of the combination therapy of the BRAF inhibitor and the MEK inhibitor in biliary tract cancer cases with the BRAF mutation [97]. In the Rare Oncology Agnostic Research (ROAR) basket trial, combination therapy with dabrafenib and trametinib shows good efficacy against biliary tract cancer cases with BRAF V600 mutations, an investigator-assessed overall response of 51%, and an independent reviewerassessed overall response of 47%.…”

Section: Brafmentioning

confidence: 99%

Tumour-Agnostic Therapy for Pancreatic Cancer and Biliary Tract Cancer

Kato

2021

Diagnostics

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The prognosis of patients with solid tumours has remarkably improved with the development of molecular-targeted drugs and immune checkpoint inhibitors. However, the improvements in the prognosis of pancreatic cancer and biliary tract cancer is delayed compared to other carcinomas, and the 5-year survival rates of distal-stage disease are approximately 10 and 20%, respectively. However, a comprehensive analysis of tumour cells using The Cancer Genome Atlas (TCGA) project has led to the identification of various driver mutations. Evidently, few mutations exist across organs, and basket trials targeting driver mutations regardless of the primary organ are being actively conducted. Such basket trials not only focus on the gate keeper-type oncogene mutations, such as HER2 and BRAF, but also focus on the caretaker-type tumour suppressor genes, such as BRCA1/2, mismatch repair-related genes, which cause hereditary cancer syndrome. As oncogene panel testing is a vital approach in routine practice, clinicians should devise a strategy for improved understanding of the cancer genome. Here, the gene mutation profiles of pancreatic cancer and biliary tract cancer have been outlined and the current status of tumour-agnostic therapy in these cancers has been reported.

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Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial

Cited by 373 publications

References 33 publications

Outcomes of neoadjuvant therapy for cholangiocarcinoma: A review of existing evidence assessing treatment response and R0 resection rate

Outcomes of neoadjuvant therapy for cholangiocarcinoma: A review of existing evidence assessing treatment response and R0 resection rate

Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials

Tumour-Agnostic Therapy for Pancreatic Cancer and Biliary Tract Cancer

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