Plasmatic BRAF-V600E allele fraction as a prognostic factor in metastatic colorectal cancer treated with BRAF combinatorial treatments

Ros, Javier; Matito, Judit; Villacampa, Guillermo; Comas, Raquel; García, Ariadna; Martini, Giulia; Baraibar, Iosune; Saoudi, Nadia; Salvà, Francesc; Martín, A. Muñoz; Antista, Maria; Toledo, Rodrigo A.; Martinelli, E.; Pietrantonio, Filippo; Boccaccino, Alessandra; Cremolini, Chiara; Dientsmann, R.; Tabernero, Josep; Vivancos, Ana; Élez, Elena

doi:10.1016/j.annonc.2023.02.016

Cited by 37 publications

(13 citation statements)

References 28 publications

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“…Similar to our findings, the concomitant KRAS mutation and amplification has a predictive effect for greater benefit from treatment in KRAS -mutated lung cancers, 48 and high allele fraction for BRAF mutation, which is an adverse prognostic factor in colorectal cancers, is associated with a higher benefit from triplet therapy with EGFR-BRAF-MEK inhibitors (OS HR = 0.17) compared to the cancers with low BRAF mutation allele frequency cancers (OS HR = 0.90). 49 Concomitant mutation and amplification could indicate oncogene addiction, but since targeted therapy for KIT -mutated AM and MM is generally not licensed and not available for broad use, it is challenging to obtain samples to validate our study. However, these considerations could be taken into account for future clinical trials design.…”

Section: Discussionmentioning

confidence: 99%

Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial

Larkin,

Marais,

Porta

et al. 2024

Cell Reports Medicine

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Section: Discussionmentioning

confidence: 99%

Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial

Larkin,

Marais,

Porta

et al. 2024

Cell Reports Medicine

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“…Recently, with the emergence of liquid biopsy as a promising method for early diagnosis, therapeutic outcome assessment and prognosis prediction of tumor, plasmatic BRAF allele fraction (AF) has been demonstrated, and validated as an accurate prognostic factor in BRAF CRC treated with BRAF inhibitors ( 20 , 21 ). Circulating tumor DNA (ctDNA)-based dynamic monitoring has outstanding significance in reflecting the response of patients with advanced CRC.…”

Section: Discussionmentioning

confidence: 99%

Partial response to crizotinib + regorafenib + PD-1 inhibitor in a metastatic BRAF V600EMT colon cancer patient with acquired C-MET amplification and TPM4-ALK fusion: a case report

Huang,

Zhang,

et al. 2024

AME Case Rep

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Background Colorectal cancer (CRC) with the Raf murine sarcoma viral oncogene homolog B ( BRAF ) V600E had a relatively poor prognosis. Anaplastic lymphoma kinase ( ALK ) fusion and the mesenchymal-to-epithelial transition factor ( MET ) amplification have been recognized as potentially important therapeutic targets in non-small cell lung cancer (NSCLC). However, both of them are of extremely lower frequencies (<2%) in metastatic CRC, and few studies have mentioned the real application of their inhibitors in CRC treatment. Case Description A 49-year-old Chinese male was diagnosed with ascending colon adenocarcinoma (cT3N+?M1) with liver metastases. The patient performed next-generation sequencing (NGS) using tissue and circulating tumor DNA (ctDNA), and the results showed a BRAF V600E mutation. He received an initial combination treatment with cetuximab, dabrafenib, and trametinib with a partial response (PR) assessment. We changed the therapy regimen on this patient several times because of the patient’s intolerance to the drugs or the inefficacy of the treatment. During this period, we detected the c-MET amplification and tropomyosin 4 ( TPM4 ) -ALK fusion by NGS after triplet targeted therapy (tislelizumab, dabrafenib, and trametinib), thus he was finally treated with programmed cell death protein 1 (PD-1) inhibitor (tislelizumab), MET/ALK inhibitor (crizotinib) plus multikinase inhibitor (regorafenib). Imageological examinations showed that PR was achieved and ctDNA sequencing results indicated a significantly reduced BRAF mutation frequency, MET amplification and TPM4-ALK fusion were undetectable. NGS analysis of peripheral blood showed a recurrence of the MET acquired resistant amplification mutation over 2 months of ongoing treatment. but the patient was assessed as PR and still under treatment of crizotinib, tislelizumab and regorafenib within good physical condition. At the last follow-up on October 2021, the patient died of symptomatic treatment fail for obstructive jaundice. The patient finally achieved 11 months overall survival. Conclusions This study reported a co-existence of a BRAF V600E mutation, c-MET amplification and TPM4-ALK fusion in a CRC patient. Administration of crizotinib combined with regorafenib and tislelizumab obtained an obvious response. Furthermore, continuous ctDNA detection appears to be a promising technique to monitor tumor burden, which may provide better clinical decision support during the disease course.

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“…The continuation of TT beyond radiological progression was infrequent ( n = 2), with a signal of prolonged disease control in one case of oligoprogression and no benefit after a brief TT-free interval in the other case, suggesting that accurate selection of patients is needed to tailor the continuation/reintroduction strategy after previous failure, possibly including molecular analyses, in accordance with growing evidence accumulated in the last years. 17 , 18 , 19 …”

Section: Discussionmentioning

confidence: 99%

Treatment of patients with BRAF-mutated metastatic colorectal cancer after progression to encorafenib and cetuximab: data from a real-world nationwide dataset

Germani,

Vetere,

Santamaria

et al. 2024

ESMO Open

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Plasmatic BRAF-V600E allele fraction as a prognostic factor in metastatic colorectal cancer treated with BRAF combinatorial treatments

Cited by 37 publications

References 28 publications

Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial

Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial

Partial response to crizotinib + regorafenib + PD-1 inhibitor in a metastatic BRAF V600EMT colon cancer patient with acquired C-MET amplification and TPM4-ALK fusion: a case report

Treatment of patients with BRAF-mutated metastatic colorectal cancer after progression to encorafenib and cetuximab: data from a real-world nationwide dataset

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