Camrelizumab plus oxaliplatin‐based chemotherapy as first‐line therapy for advanced biliary tract cancer: A multicenter, phase 2 trial

Chen, Xinni; Qin, Shukui; Gu, Shanzhi; Ren, Zhenggang; Chen, Zhendong; Xiong, Jianping; Liu, Ying; Meng, Zhiqiang; Zhang, Xiao; Wang, Linna; Zhang, Xiaojing; Zou, Jianjun

doi:10.1002/ijc.33751

Cited by 36 publications

(34 citation statements)

References 48 publications

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“…This is the first report on the efficacy and safety of camrelizumab in combination with apatinib in patients with cholangiocarcinoma. Most studies on immunotherapy for advanced biliary tract cancer are in the exploratory stage, and these findings demonstrated promising therapeutic efficacy and relatively manageable toxicity, which needs further trials ( 61 , 62 ).…”

Section: Clinical Efficacy In Liver Cancer and Cholangiocarcinomamentioning

confidence: 99%

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Huang

Zhang

et al. 2022

Front. Immunol.

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Digestive system malignancies are one of the primary causes of cancer-related death. Meanwhile, angiogenesis has been proved to play an important role in the process of cancer neovascularization. Apatinib, a novel targeted antiangiogenic molecule, could generate highly selective competition in the vascular endothelial growth factor receptor-2, involved in tumor progression and metastasis. It has been implied as a promising cancer treatment agent that can prevent tumor cell proliferation meanwhile inhibit tumor angiogenesis. Furthermore, completed clinical trials demonstrated that apatinib could prolong the progression-free survival and overall survival in advanced gastric cancer and primary liver cancer. Recent studies revealed that apatinib had a synergistic effect with immunotherapy as a second-line and third-line treatment regimen for some other cancers. In this review, we summarize the pharmacological properties of apatinib and the latest clinical application in chemotherapy-refractory patients with advanced digestive system cancer. Based on the comparable survival results, the molecular mechanisms of apatinib are prospective to include the antiangiogenic, apoptosis-inducing, and autophagy-inducing properties in the corresponding signaling pathway. Treatment of apatinib monotherapy or combination immunotherapy remains the optimal option for patients with digestive system malignancies in the future.

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Section: Clinical Efficacy In Liver Cancer and Cholangiocarcinomamentioning

confidence: 99%

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Huang

Zhang

et al. 2022

Front. Immunol.

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“…BTC patients treated by single ICI displayed dissatisfied ORR ranging from 5.8% to 22% (9, 10). However, recent research of immune-combined therapy in BTC showed an increasing ORR amount to 43.8%~54% (25,26). Whether and how chemotherapy facilitate the anti-PD1 therapy needs exploration.…”

Section: Discussionmentioning

confidence: 99%

Immune-related RNA signature predicts outcome of PD-1 inhibitor-combined GEMCIS therapy in advanced intrahepatic cholangiocarcinoma

Zeng¹,

Yuan²,

Chen³

et al. 2022

Front. Immunol.

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BackgroundImmune checkpoint inhibitor (ICI)-combined chemotherapy in advanced intrahepatic cholangiocarcinoma has been proved to have more efficacy in a series of clinical trials. However, whether the tumor microenvironment (TME) plays a vital role in immune-combined therapy has not been rigorously evaluated.MethodsFirstly, we assayed the immunogenic properties of GEM-based chemotherapy. Then, 12 ICC patients treated with PD-1 inhibitor (sintilimab) combined with gemcitabine and cisplatin (GemCis) from a phase 2 clinical trial (ChiCTR2000036652) were included and their immune-related gene expression profiles were analyzed using RNA from baseline tumor samples. Immune-related signature correlating with clinical outcome was identified according to the 12 ICC patients, and its predictive value was validated in an ICC cohort with 26 patients. Multiplexed immunofluorescence (mIF) and flow cytometry (FCM) analysis were performed to evaluate the immune-related molecules with therapeutic outcomes.ResultsGEM-based chemotherapy induced immunogenic cell death of cholangiocarcinoma cells, together with increased CD274 expression. In an ICC cohort, we found that upregulation of immune-checkpoint molecules and immune response-related pathways were significantly related to better clinical outcome. On the contrary, baseline immune-cell proportions in tumor tissues did not show any correlation with clinical benefit between responders and non-responders. Immune-related signature (including six genes) correlating with clinical outcome was identified according to the 12 ICC patients, and its predictive value was validated in a small ICC cohort with 26 patients.ConclusionImmune-related RNA signature predicts the outcome of PD-1 inhibitor-combined GEMCIS therapy in advanced intrahepatic cholangiocarcinoma, which could be tested as a biomarker for immune-chemotherapy in the future.

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“…These promising results suggest that camrelizumab plus oxaliplatin-based chemotherapy could be a new first-line therapy for advanced BTC. 68 Another phase 1 study of durvalumab (an anti-PD-L1) and tremelimumab, an anti-CTLA-4, reported similar, promising results. Durvalumab monotherapy cohorts achieved a median OS of 8.1 months and dual therapy achieved 10.1 months, suggesting its potential as a novel second-line therapy.…”

Section: Ici Combinations and In Synergy With Chemotherapymentioning

confidence: 91%

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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Camrelizumab plus oxaliplatin‐based chemotherapy as first‐line therapy for advanced biliary tract cancer: A multicenter, phase 2 trial

Cited by 36 publications

References 48 publications

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Immune-related RNA signature predicts outcome of PD-1 inhibitor-combined GEMCIS therapy in advanced intrahepatic cholangiocarcinoma

Combination Therapies for Advanced Biliary Tract Cancer

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