Annals of oncology : official journal of the European Society for Medical Oncology
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Randomized Controlled Trial Multicenter Study
Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial.
FIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. The consensus molecular subgroups (CMS) are grouping CRC samples according to their gene-signature in four different subtypes. Relevance of CMS for the treatment of mCRC has yet to be defined. ⋯ CMS classification is prognostic for mCRC. Prolonged OS induced by FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in the FIRE-3 study appears to be driven by CMS3 and CMS4. CMS classification provides deeper insights into the biology to CRC, but at present time has no direct impact on clinical decision-making.The FIRE-3 (AIO KRK-0306) study had been registered at ClinicalTrials.gov: NCT00433927.
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TRK fusions are oncogenic drivers of various adult and paediatric cancers. The first-generation TRK inhibitors, larotrectinib and entrectinib, were granted landmark, tumour-agnostic regulatory approvals for the treatment of these cancers in 2018 and 2019, respectively. Brisk and durable responses are achieved with these drugs in patients, including those with locally advanced or metastatic disease. ⋯ This underscores the utility of sequential TRK inhibitor use in select patients, a paradigm that parallels the use of targeted therapies in other oncogenic driver-positive cancers, such as ALK fusion-positive lung cancers. While TRK inhibitors have a favourable overall safety profile, select on-target adverse events, including weight gain, dizziness/ataxia and paraesthesias, are occasionally observed and should be monitored in the clinic. These side-effects are likely consequences of the inhibition of the TRK pathway that is involved in the development and maintenance of the nervous system.