Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study

Oh, Do‐Youn; Lee, Kyung-Hun; Lee, Dae-Won; Yoon, Jeesun; Kim, Tae-Yong; Bang, Jae Seung; Nam, Ah-Rong; Oh, Kyoung-Seok; Kim, Jae-Min; Lee, Young; Guthrie, Violeta Beleva; McCoon, Patricia; Liu, Weimin; Wu, Song; Qu, Zhilin; Rebelatto, Marlon C.; Kim, Jin Won

doi:10.1016/s2468-1253(22)00043-7

Cited by 219 publications

(157 citation statements)

References 28 publications

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“…A small phase II trial of gemcitabine and cisplatin plus durvalumab with or without tremelimumab suggests adding dual immunotherapy upfront with chemotherapy may not provide additional benefits to single-agent immunotherapy agents in patients with advanced biliary tract cancer. 7 In conclusion, we reported the first case series on the use of dual immunotherapy with cholangiocarcinoma in patients who had progressed on single-agent immunotherapy with pembrolizumab. It is proof of the concept that sequential immunotherapy can be beneficial after progression on singleagent immunotherapy.…”

Section: Discussionmentioning

confidence: 84%

“…Should we begin to use dual immunotherapy with chemotherapy or reserve dual immunotherapy as a sequential therapy option for our patients? A small phase II trial of gemcitabine and cisplatin plus durvalumab with or without tremelimumab suggests adding dual immunotherapy upfront with chemotherapy may not provide additional benefits to single-agent immunotherapy agents in patients with advanced biliary tract cancer 7…”

Section: Discussionmentioning

confidence: 99%

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Durable Responses in Patients With Advanced Cholangiocarcinoma on Sequential Dual-agent Immunotherapy After Progressing on Single-agent Immunotherapy

Kaakour¹,

Hagopian²,

Lee³

et al. 2022

American Journal of Clinical Oncology

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Objectives: Biliary tract tumors have a poor prognosis despite advancements in targeted therapies. More recent studies have started to investigate the use of combination immunotherapy in advanced biliary cancers. However, currently, there are no clinical trials investigating the use of dual-agent immunotherapy with ipilimumab and nivolumab as a sequential treatment after patients have progressed on single-agent immunotherapy. In this case series, we discussed 3 patients with advanced cholangiocarcinoma who have an objective response to dualagent immunotherapy with ipilimumab and nivolumab after having disease progression on pembrolizumab and multiple other failed lines of treatment.Materials and Methods: A case series, including 3 patients treated at the University of California, Irvine Chao Family Comprehensive Cancer Center, was completed.Results: Although none of the 3 patients had microsatellite instability or high tumor-mutation burden and were not necessarily predicted to have a response to dual-agent immunotherapy, all 3 patients had an objective radiographic and/or tumor-marker response to a combination of ipilimumab and nivolumab.Conclusions: This case series serves as proof of the concept that sequential immunotherapy can be beneficial after progression on singleagent immunotherapy for patients with advanced cholangiocarcinoma. This study can also serve as the foundation to build further tests on the true effectiveness and ideal duration of sequential therapy with dual immunotherapy agents.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Durable Responses in Patients With Advanced Cholangiocarcinoma on Sequential Dual-agent Immunotherapy After Progressing on Single-agent Immunotherapy

Kaakour¹,

Hagopian²,

Lee³

et al. 2022

American Journal of Clinical Oncology

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“…Recently, the TOPAZ-1 trial [ 84 ] showed that the addition of durvalumab, an immune checkpoint inhibitor targeting PD-L1, in combination with gemcitabine and cisplatin improved survival in treatment-naïve patients with CCA. As a result, immunotherapy has been proven to play a role in unselected patients with CCA.…”

Section: Future Challenges and Other Novel Treatmentsmentioning

confidence: 99%

Precision Medicine in Cholangiocarcinoma: Past, Present, and Future

Cheng

Chen

2022

Life

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Cholangiocarcinoma (CCA), or biliary tract cancer, has a poor prognosis. The median survival time among patients with CCA is under 2 years from diagnosis, and the global 5-year survival rate is only 10%. First-line therapy with chemotherapeutic agents, gemcitabine plus cisplatin, has traditionally been used to treat unresectable advanced CCA. In recent years, precision medicine has become a mainstream cancer treatment due to innovative next-generation sequencing technology. Several genetic alterations, including mutations, gene fusions, and copy number variations, have been found in CCA. In this review, we summarized the current understanding of genetic profiling in CCA and targeted therapy in CCA. Owing to the high heterogeneity of CCA, tumor microenvironmental factors, and the complexity of tumor biology, only pemigatinib, infigratinib, ivosidenib, larotrbctinib, and entrectinib are currently approved for the treatment of CCA patients with fibroblast growth factor receptor 2 gene (FGFR2) fusion, isocitrate dehydrogenase gene (IDH1) mutation, and neurotrophin receptor tyrosine kinase gene (NRTK) fusion, respectively. Additional targeted therapies, including other FGFR2 inhibitors, PI3K/AKT/mTOR inhibitors, and BRAF-directed targeted therapy, have been discussed for the management of CCA, and immune checkpoint inhibitors, particularly pembrolizumab, can be administered to patients with high microsatellite instability tumors. There is a further need for improvement in precision medicine therapies in the treatment of CCA and discuss the approved and potential targeted therapies for CCA.

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“…The overall median PFS was 12.1 months and the median OS was 18.4 months, which was promising compared with classical chemotherapy. 70 However, the study did not include a control group. The differences of OS or PFS in the three regimens were not significant.…”

Section: Ici Combinations and In Synergy With Chemotherapymentioning

confidence: 99%

Combination Therapies for Advanced Biliary Tract Cancer

Zeng¹,

Mao²,

Zhang³

et al. 2022

J Clin Transl Hepatol

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Biliary tract cancers (BTCs) are a group of malignant neoplasms that have recently increased in incidence and have a poor prognosis. Surgery is the only curative therapy. However, most patients are only indicated for palliative therapy because of advanced-stage disease at diagnosis and rapid progression. The current first-line treatment for advanced BTC is gemcitabine and cisplatin chemotherapy. Nonetheless, many patients develop resistance to this regimen. Over the years, few chemotherapy regimens have managed to improve the overall survival of patients. Accordingly, novel therapies such as targeted therapy have been introduced to treat this patient population. Extensive research on tumorigenesis and the genetic profiling of BTC have revealed the heterogenicity and potential target pathways, such as EGFR, VEGF, MEK/ERK, PI3K and mTOR. Moreover, mutational analysis has documented the presence of IDH1, FGFR2, HER2, PRKACA, PRKACB, BRAF, and KRAS gene aberrations. The emergence of immunotherapy in recent years has expanded the treatment landscape for this group of malignancies. Cancer vaccines, adoptive cell transfer, and immune checkpoint inhibitors have been extensively investigated in trials of BTC. Therefore, patient stratification and a combination of various therapies have become a reasonable and important clinical strategy to improve patient outcomes. This review elaborates the literature on combined treatment strategies for advanced BTC from the past few years and ongoing clinical trials to provide new inspiration for the treatment of advanced BTC.

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Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study

Cited by 219 publications

References 28 publications

Durable Responses in Patients With Advanced Cholangiocarcinoma on Sequential Dual-agent Immunotherapy After Progressing on Single-agent Immunotherapy

Durable Responses in Patients With Advanced Cholangiocarcinoma on Sequential Dual-agent Immunotherapy After Progressing on Single-agent Immunotherapy

Precision Medicine in Cholangiocarcinoma: Past, Present, and Future

Combination Therapies for Advanced Biliary Tract Cancer

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