Regorafenib–avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial

Cousin, Sophie; Cantarel, Coralie; Guégan, Jean-Philippe; Mazard, Thibault; Gomez‐Roca, Carlos; Metges, Jean-Philippe; Bellera, C.; Adenis, Antoine; Korakis, Iphigénie; Poureau, Pierre-Guillaume; Bourcier, Kévin; Toulmonde, Maud; Kind, Michèle; Rey, Christophe; Auzanneau, Céline; Bessede, Alban; Soubeyran, Isabelle; Italiano, Antoîne

doi:10.1016/j.ejca.2021.11.012

Cited by 28 publications

(30 citation statements)

References 27 publications

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“…24,25 Several small nonrandomised or single-arm studies on ICI combination therapy with variations in the individual agents showed acceptable or good outcomes. [11][12][13][14] However, almost all previous studies were conducted on heterogeneous BTC tumours. In turn, our study focussed only on ICCs to obtain evidence that can help inform treatment decisions for this specific malignancy.…”

Section: Discussionmentioning

confidence: 99%

Effect of different PD‐1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma

Lei

et al. 2023

Aliment Pharmacol Ther

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SummaryBackgroundImmune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC).AimTo compare the effect of different anti‐PD‐1 combination therapies as the first‐line treatments for uICC.MethodsThis study included 318 patients who received chemotherapy alone (Chemo), anti‐PD‐1 plus chemotherapy (ICI‐chemo), anti‐PD‐1 plus targeted therapy (ICI‐target) or anti‐PD‐1 plus targeted therapy and chemotherapy (ICI‐target‐chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety.ResultsPatients with ICI‐chemo (median PFS [mPFS], 6.3 months; HR: 0.61, 95% CI: 0.42–0.88; p = 0.008; median OS [mOS], 10.7 months; HR: 0.61, 95% CI: 0.39–0.94; p = 0.026), ICI‐target (7.2 months; HR: 0.54, 95% CI: 0.36–0.80; p = 0.002; 15.8 months; HR: 0.54, 95% CI: 0.35–0.84; p = 0.006) or ICI‐target‐chemo (6.9 months; HR: 0.65, 95% CI: 0.47–0.90; p = 0.009; 14.4 months; HR: 0.47, 95% CI: 0.31–0.70; p < 0.001) achieved better clinical outcomes than those with Chemo (3.8 months; 9.3 months). ICI‐target was not inferior to ICI‐chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55–1.42; p = 0.614; HR for OS: 0.89, 95% CI: 0.51–1.55; p = 0.680). ICI‐target‐chemo yielded similar prognoses as ICI‐chemo (HR for PFS: 1.07, 95% CI: 0.70–1.62; p = 0.764; HR for OS: 0.77, 95% CI: 0.45–1.31; p = 0.328) and ICI‐target (HR for PFS: 1.20, 95% CI: 0.77–1.88; p = 0.413; HR for OS: 0.86, 95% CI: 0.51–1.47; p = 0.583) but resulted in more adverse events (p < 0.001; p = 0.010). Multivariable and propensity score analyses supported these findings.ConclusionsAmong patients with uICC, ICI‐chemo or ICI‐target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI‐target‐chemo.

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Section: Discussionmentioning

confidence: 99%

Effect of different PD‐1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma

Lei

et al. 2023

Aliment Pharmacol Ther

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“…REGOMUNE (NCT03475953) is a single arm, multicentric phase II trial investigating the safety and efficacy of regorafenib (160 mg daily for 3 weeks with 1 week rest) in combination with avelumab (once every 2 weeks) in patients with various solid tumors. At present, the results of the GIST subgroup have not been disclosed, but synergistic anti-tumor effect has been shown in biliary tract tumors and colorectal cancer ( 108 , 109 ).…”

Section: Agent Combination Based On Different Strategiesmentioning

confidence: 95%

An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors

Sun

Yue

2022

Front. Oncol.

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Platelet-derived growth factor receptor A (PDGFRA) mutations occur in approximately 10–15% of gastrointestinal stromal tumors (GISTs). These tumors with PDGFRA mutations have a different pathogenesis, clinical characteristics, and treatment response compared to tumors with receptor tyrosine kinase protein (KIT) mutations (60–70%). Many clinical studies have investigated the use of tyrosine kinase inhibitors mainly in patients with KIT mutations; however, there is a lack of attention to the PDGFRA-mutated molecular subtype. The main effective inhibitors of PDGFRA are ripretinib, avapritinib, and crenolanib, and their mechanisms and efficacy in GIST (as confirmed in clinical trials) are described in this review. Some multi-targeted tyrosine kinase inhibitors with inhibitory effects on this molecular subtype are also introduced and summarized in this paper. This review focuses on PDGFRA-mutated GISTs, introduces their clinical characteristics, downstream molecular signaling pathways, and existing resistance mechanisms. We focus on the most recent literature that describes the development of PDGFRA inhibitors and their use in clinical trials, as well as the potential benefits from different combination therapy strategies.

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“…Overexpression of PD-L1 and indoleamine 2,3-dioxygenase were associated with improved outcomes. Based on these results, further investigations in selected patients based on the characteristics of the TME are needed [ 61 ]. In another ongoing phase I/II clinical trial, the combination of Regorafenib and Durvalumab (MEDI4736) in patients with advanced BTC tumors is under investigation (NCT04781192).…”

Section: Clinical Studies Targeting Both Angiogenesis and Immune Chec...mentioning

confidence: 99%

Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues

Schirizzi

Leonardis

Lorusso

et al. 2023

Cancers

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Although biliary tract cancers are traditionally considered rare in Western countries, their incidence and mortality rates are rising worldwide. A better knowledge of the genomic landscape of these tumor types has broadened the number of molecular targeted therapies, including angiogenesis inhibitors. The role of immune checkpoint inhibitors (ICIs) could potentially change the first-line therapeutic approach, but monotherapy with ICIs has shown disappointing results in CCA. Several clinical trials are evaluating combination strategies that include immunotherapy together with other anticancer agents with a synergistic activity. The tumor microenvironment (TME) composition plays a pivotal role in the prognosis of BTC patients. The accumulation of immunosuppressive cell types, such as tumor-associated macrophages (TAMs) and regulatory T-cells, together with the poor infiltration of cytotoxic CD8+ T-cells, is known to predispose to a poor prognosis owing to the establishment of resistance mechanisms. Likewise, angiogenesis is recognized as a major player in modulating the TME in an immunosuppressive manner. This is the mechanistic rationale for combination treatment schemes blocking both immunity and angiogenesis. In this scenario, this review aims to provide an overview of the most recent completed or ongoing clinical trials combining immunotherapy and angiogenesis inhibitors with/without a chemotherapy backbone.

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Regorafenib–avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial

Cited by 28 publications

References 27 publications

Effect of different PD‐1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma

Effect of different PD‐1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma

An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors

Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues

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