LBA25 FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer

Dasari, N.A.; García‐Carbonero, Rocío; Fernandez, M.E. Elez; Yoshino, T.; Sobrero, Alberto; Yao, J.C.; García‐Alfonso, Pilar; Kocsis, Judit; Gracián, Antonio Cubillo; Bianchi, Andrea Sartore; Satoh, Takeshi; Randrian, Violaine; Tomášek, Jiří; Chong, Geoffrey; Yang, Z.; Schelman, W.; Kania, M.; Tabernero, Josep; Eng, Cathy

doi:10.1016/j.annonc.2022.08.021

Cited by 28 publications

(27 citation statements)

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“…A most recent disclosure of phase III, multiregional clinical trial, FRESCO-2 trial (NCT0432253) in patients with refractory mCRC for more than third-line treatment, had showed that fruquintinib not only significantly improved OS (median: 7.4 m vs. 4.8 m; HR=0.66; [95% CI: 0.55, 0.80]; p<0.001) but also PFS (median: 3.7 m vs. 1.8 m; HR=0.32; [95% CI: 0.27, 0.39]; p<0.001) as compared to placebo. This evidence signifies the clinical benefit of fruquintinib even for mCRC treatment beyond third-line ( 18 ).…”

Section: Discussionmentioning

confidence: 84%

A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer

Jin¹,

Li²,

Lin³

et al. 2022

Front. Oncol.

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ObjectiveThe objective of this study was to assess the comparative efficacy in third-line setting for metastatic CRC (mCRC) patients using matched population of FRESCO trial with fruquintinib and real-world data with other TKIs.Materials and methodsThe arm of fruquintinib from the FRESCO phase III trial (NCT02314819) included the data of patients with metastatic CRC that progressed after at least two lines of chemotherapy and received fruquintinib treatment. An external control arm was constructed using real-world data (RWD) of patients who received other TKIs based on key eligibility criteria of FRESCO. The baseline characteristics of two arms was balanced by propensity score matching (PSM). The Kaplan–Meier method and Cox proportional hazard model was used to evaluate progression free survival (PFS) and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), respectively.ResultsOverall, 128 patients were successfully matched by PSM in each, fruquintinib and other TKIs group. The patients in fruquintinib group showed significant increase in median PFS than other TKIs (3.71 vs. 2.49 months, HR = 0.67, 95%CI, 0.48-0.94, p = 0.019). In the subgroup analysis, fruquintinib showed a significant benefit in PFS compared with other TKIs among patients undergoing two or three previous chemotherapy regimens (HR 0.58, 95%CI 0.40-0.84; p=0.004), with rectum as primary disease site (HR 0.52, 95%CI 0.31-0.87; p=0.013), with left sided primary tumor location (HR 0.62, 95%CI 0.42-0.90; p=0.011), with multiple metastasis sites (HR 0.68, 95%CI 0.48-0.97; p=0.034) and with lung metastasis (HR 0.65, 95%CI 0.43-0.98; p=0.042).ConclusionWith the approach of establishing the external control arm from RWD, this study has demonstrated that treatment with fruquintinib significantly prolonged PFS as compared to other TKIs in patients as third-line mCRC treatment.

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Section: Discussionmentioning

confidence: 84%

A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer

Jin¹,

Li²,

Lin³

et al. 2022

Front. Oncol.

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“…The continuum of care is ever evolving in the treatment of patients with mCRC. The results of the recently completed FRESCO-2 trial with fruquintinib in refractory mCRC show a significant and clinically meaningful improvement in OS ( 76 ). Regorafenib and trifluridine/tipiracil are other current treatment options beyond the second line that have been shown to improve OS in patients previously treated with chemotherapy or targeted therapy ( 5 ).…”

Section: Discussionmentioning

confidence: 99%

Rechallenge with anti-EGFR therapy to extend the continuum of care in patients with metastatic colorectal cancer

et al. 2023

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In patients with RAS wild-type metastatic colorectal cancer (mCRC), an anti-epidermal growth factor receptor (EGFR) monoclonal antibody plus chemotherapy is a standard option for treatment in the first-line setting. Patients who progress while on treatment with anti-EGFR-based therapy can be resistant to further anti-EGFR treatment, but evidence suggests that the anti-EGFR-resistant clones decay, thereby opening the potential for rechallenge or reintroduction in later lines of treatment. Results from recent clinical studies have shown that some patients with mCRC who are rechallenged with anti-EGFR monoclonal antibodies exhibit durable responses. While other therapies have demonstrated improved overall survival in chemorefractory mCRC over the past decade, rechallenge with anti-EGFR monoclonal antibodies in later lines of treatment represents a new option that deserves further investigation in clinical trials. In this review, we summarize the molecular rationale for rechallenge or reintroduction in patients with mCRC who have progressed on earlier-line anti-EGFR treatment and examine the current evidence for using liquid biopsy as a method for selecting rechallenge as a therapeutic option. We also provide an overview of published trials and trials in progress in this field, and outline the potential role of rechallenge in the current clinical setting.

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“…Compared with placebo, fruquintinib improved OS (7.4 months versus 4.8 months, p < 0.001) and PFS (3.7 months versus 1.8 months, p < 0.001) with tolerable safety profile (grade ⩾3 AE 62.7% versus 50.4%). 61 …”

Section: Vegf Inhibitionmentioning

confidence: 99%

New developments in targeted therapy for metastatic colorectal cancer

Wong

B.Y.²,

Lui

2023

Ther Adv Med Oncol

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Colorectal cancer (CRC) is the second most lethal cancer worldwide and the prognosis of metastatic CRC (mCRC) remains poor. Recent advancements in translational research have led to the identification of several new therapeutic targets and improved the treatment outcome of patients with tumours harbouring BRAF V600E mutation, ( HER2) ErBB2 alterations, NTRK gene fusions and KRAS(G12C) mutation. Improved understanding towards the mechanism of resistance to targeted therapy such as anti-epidermal growth factor receptor antibodies and the evolving role of therapeutic monitoring with circulating tumour DNA (ctDNA) has enabled the longitudinal tracking of clonal evolution during treatment and the individualization of subsequent treatments. To broaden the community-based implementation of precision oncology in directing targeted therapies for patients with gastrointestinal cancers including mCRC, the feasibility of ‘Master Protocols’ that utilizes ctDNA-based genotyping platforms is currently being evaluated. Such protocols encompass both observational and interventional clinical trials of novel targeted therapies conducted within a large clinical trial network. In this review, we will discuss the latest developments in targeted therapies, and therapeutic strategies for overcoming acquired drug resistance in patients with mCRC.

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LBA25 FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer

Cited by 28 publications

References 0 publications

A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer

A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer

Rechallenge with anti-EGFR therapy to extend the continuum of care in patients with metastatic colorectal cancer

New developments in targeted therapy for metastatic colorectal cancer

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