Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study

Dasari, Arvind; García‐Carbonero, Rocío; Élez, Elena; Yoshino, Takayuki; Sobrero, Alberto; Yao, James C.; García‐Alfonso, Pilar; Kocsis, Judit; Gracián, Antonio Cubillo; Satoh, Taroh; Randrian, Violaine; Tomášek, Jiří; Chong, Geoff; Paulson, Andrew Scott; Masuishi, Toshiki; Jones, Jeremy C.; Csőszi, Tibor; Cremolini, Chiara; Ghiringhelli, François; Shergill, Ardaman; Hochster, Howard S.; Krauss, John C.; Bassam, Ali; Ducreux, Michel; Faugeras, Laurence; Kasper, Stefan; Cutsem, Éric Van; Arnold, Dirk; Nanda, Shivani; Zhao, Yong; Schelman, William R.; Kania, Marek; Tabernero, Josep; Eng, Cathy

doi:10.1016/s0140-6736(23)00772-9

Cited by 75 publications

(47 citation statements)

References 17 publications

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“…22,23 In the continuum of care for mCRC, even in later lines of treatment, fluoropyrimidine-based therapies and the blockade of angiogenesis are the main therapeutic choices. [24][25][26][27] The use of the antiangiogenic drugs regorafenib and fruquintinib, or the chemotherapy compound trifluridinetipiracil, is associated with a modest but significant clinical benefit compared with placebo. 24,26,27 To date, SUNLIGHT is the only randomized phase 3 trial that demonstrated an improvement in both PFS and OS over an active treatment in patients with chemorefractory mCRC.…”

Section: Discussionmentioning

confidence: 99%

“…[24][25][26][27] The use of the antiangiogenic drugs regorafenib and fruquintinib, or the chemotherapy compound trifluridinetipiracil, is associated with a modest but significant clinical benefit compared with placebo. 24,26,27 To date, SUNLIGHT is the only randomized phase 3 trial that demonstrated an improvement in both PFS and OS over an active treatment in patients with chemorefractory mCRC. 25 In this scenario, novel and more effective therapeutic options are required.…”

Section: Discussionmentioning

confidence: 99%

“…22,24,26,27 Furthermore, the available options display mainly a cytostatic activity (ORR, 1%-6%). [24][25][26][27] With all the limitations for indirect cross-trial comparisons, in this study we report an OS Graphs show progression-free survival (A) and overall survival (B). The median progression-free survival was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months).…”

Section: Discussionmentioning

confidence: 99%

“…The expected survival for patients with refractory mCRC who received trifluridine-tipiracil, regorafenib, or fruquintinib as single agents is approximately 7 to 9 months, whereas patients who were treated with trifluridine-tipiracil plus bevacizumab as third-line therapy had a median OS of 10.8 months . Furthermore, the available options display mainly a cytostatic activity (ORR, 1%-6%) .…”

Section: Discussionmentioning

confidence: 99%

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Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

Ciardiello,

Martinelli,

Troiani

et al. 2024

JAMA Netw Open

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ImportanceThe available evidence regarding anti–epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies.ObjectiveTo evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA RAS/BRAF wt mCRC.Design, Setting, and ParticipantsThis nonrandomized controlled trial used a pooled analysis of individual patient data from patients with RAS/BRAF wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28.1 [25.8-35.0] months).InterventionPatients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy.Main Outcomes and MeasuresOverall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated. Exploratory subgroup analysis evaluating several clinical variables was performed. Safety was reported.ResultsOverall, 114 patients with RAS/BRAF wt ctDNA mCRC (median [IQR] age, 61 [29-88] years; 66 men [57.9%]) who received anti-EGFR rechallenge as experimental therapy (48 received cetuximab plus avelumab, 26 received trifluridine-tipiracil plus panitumumab, 13 received irinotecan plus cetuximab, and 27 received panitumumab monotherapy) were included in the current analysis. Eighty-three patients (72.8%) had received 2 previous lines of therapy, and 31 patients (27.2%) had received 3 or more previous lines of therapy. The ORR was 17.5% (20 patients), and the DCR was 72.3% (82 patients). The median PFS was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months). The subgroup of patients without liver involvement had better clinical outcomes. The median PFS was 5.7 months (95% CI, 4.8-6.7 months) in patients without liver metastasis compared with 3.6 months (95% CI, 3.3-3.9 months) in patients with liver metastasis (hazard ratio, 0.56; 95% CI, 0.37-0.83; P = .004). The median OS was 17.7 months (95% CI, 13-22.4 months) in patients without liver metastasis compared with 11.5 months (95% CI, 9.3-13.9 months) in patients with liver metastasis (hazard ratio, 0.63; 95% CI, 0.41-0.97; P = .04). Treatments showed manageable toxic effects.Conclusions and RelevanceThese findings suggest that anti-EGFR rechallenge therapy has promising antitumor activity in patients with refractory ctDNA RAS/BRAF wt mCRC. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival.Trial RegistrationClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

Ciardiello,

Martinelli,

Troiani

et al. 2024

JAMA Netw Open

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“…In China, TAS-102 ( 6 ), regorafenib ( 7 ), and fruquintinib ( 8 ) have been approved as third-line regimens for mCRC. However, no single regimen shows superior survival ( 9 - 11 ). Meanwhile, the current standard treatments also have certain limitations, such as high cost and side effects, including hypertension and hand and foot skin reaction.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of gemcitabine plus raltitrexed or S-1 versus standard third-line therapies in metastatic colorectal cancer: a retrospective cohort study

Tao,

Zhang,

Wang

et al. 2024

J Gastrointest Oncol

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Background After the failure of standard first- and second-line treatments, including oxaliplatin, irinotecan, and 5-fluorouracil (5-FU) combined with targeted drugs, the currently recommended third-line regimens for metastatic colorectal cancer (mCRC) include TAS-102, regorafenib, and fruquintinib. However, these regimens have the drawbacks of mediocre efficacy, substantive side effects, and high cost. Therefore, more effective, economical regimens with fewer side effects are needed in clinical practice. In this study, we assessed the efficacy and safety of gemcitabine plus raltitrexed or S-1 as a third- or later-line treatment in comparison to those of standard third-line therapies for patients with mCRC. Methods Patients with previous failures of at least two lines of standard therapy with oxaliplatin, 5-FU, irinotecan, or capecitabine combined with targeted drugs were included. The participants received standard third-line therapies (including TAS-102, regorafenib, and fruquintinib) or gemcitabine plus raltitrexed or S-1 until disease progression, death, or intolerable toxicity arose. Imaging follow-up was performed every 3 months during their treatment. Progression-free survival (PFS) and overall survival (OS) were recorded. Cox regression analysis was used to investigate the potential predictors of survival. Results From April 2018 to October 2022, 60 patients with mCRC were enrolled in our study. The numbers of patients in the chemotherapy, fruquintinib, regorafenib, and TAS-102 groups were 13, 15, 17, and 15, respectively; the median OS of the four groups was 7.4, 6.1, 8.3, and 6.7 months (P=0.384), respectively; the median PFS was 4.1, 3.4, 4.4, and 2.3 months (P=0.656), respectively; the overall response rate was 7.69%, 6.67%, 0.00%, and 13.33%, respectively; and the disease control rate was 61.54%, 60.00%, 70.59%, and 60.00%, respectively. Additionally, multivariate analysis revealed that primary lesion located in the rectum was adverse independent prognostic factors for OS. A typical case is presented in this article. Conclusions The gemcitabine plus raltitrexed or S-1 regimen is a potential regimen with tolerable adverse reactions and low cost for patients with mCRC.

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Comprehensive pancancer analysis reveals that LPCAT1 is a novel predictive biomarker for prognosis and immunotherapy response

Gao,

Zhu,

et al. 2024

Apoptosis

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Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study

Cited by 75 publications

References 17 publications

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

Efficacy and safety of gemcitabine plus raltitrexed or S-1 versus standard third-line therapies in metastatic colorectal cancer: a retrospective cohort study

Comprehensive pancancer analysis reveals that LPCAT1 is a novel predictive biomarker for prognosis and immunotherapy response

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