JSCO—ESMO—ASCO—JSMO—TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions

Abstract

A Japan Society of Clinical Oncology (JSCO)-hosted expert meeting was held in Japan on 27 October 2019, which comprised experts from the JSCO, the Japanese Society of Medical Oncology (JSMO), the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the Taiwan Oncology Society (TOS). The purpose of the meeting was to focus on what we have learnt from both microsatellite instability (MSI)/ deficient mismatch repair (dMMR) biomarkers in predicting the efficacy of anti-programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) immunotherapy, and the neurotrophic tyrosine receptor kinase (NTRK) gene fusions in predicting the efficacy of inhibitors of the tropomyosin receptor kinase (TRK) proteins across a range of solid tumour types. The recent regulatory approvals of the anti-PD-1 antibody pembrolizumab and the TRK inhibitors larotrectinib and entrectinib, based on specific tumour biomarkers rather than specific tumour type, have heralded a paradigm shift in cancer treatment approaches. The purpose of the meeting was to develop international expert consensus recommendations on the use of such tumour-agnostic treatments in patients with solid tumours. The aim was to generate a reference document for clinical practice, for pharmaceutical companies in the design of clinical trials, for ethics committees in the approval of clinical trial protocols and for regulatory authorities in relation to drug approvals, with a particular emphasis on diagnostic testing and patient selection.

Prognostic and immune regulating roles of YIF1B in Pan-Cancer: a potential target for both survival and therapy response evaluation

“…We have also demonstrated a link between YIF1B expression and TMB and MSI in some cancer types, and certain tumors also exhibit co-expression of YIF1B with the major MMR genes and methylation transferases. Previous studies have correlated TMB and MSI to patients' drug responses, especially for drugs that target immune checkpoint inhibitors, such as a TGF-β antagonist and PD-1 inhibitor [27][28][29][30][31][32]. We propose, therefore, that YIF1B could be deployed as an additional indicator for immune therapy evaluation of cancer patients after administration.…”

Immunotherapy for Early Stage Colorectal Cancer: A Glance into the Future

“…Considering MSI/dMMR as inclusion criterion for clinical trial enrollment, it is worthy to note that the frequency of MSI/dMMR misdiagnosis is not rare in real-life practice routine [28]. Therefore, attention should be devoted in MSI/dMMR diagnostic methods with potentially a systematic central review [29][30][31]. Two standard reference methods, namely immunohistochemistry (IHC) and polymerase chain reaction (PCR), are recommended for the detection of MSI/dMMR status.…”

“…Nonetheless, the diagnostic accuracy of NGS-based algorithms is not as certain as these of IHC and PCR. Moreover, the applicability of NGS approaches in a real-life routine has not been demonstrated, and they should only be carried out at selected specialist centres or through validated central laboratory methods [30].…”

“…All in all, the most relevant approach for MSI/dMMR testing in the context of clinical trial enrollment of localized CRC patients seems to be an upfront testing with IHC using a four-antibody panel (immunostaining of MLH1, PMS2, MSH2, and MSH6 proteins) followed by molecular approaches (PCR) when IHC is equivocal [30][31][32] [26,39]. Moreover, 90% of patients with stage II MSI/dMMR CC are cured by surgery alone [40].…”

Role of Immune Checkpoint Inhibitors in Gastrointestinal Malignancies

“…Immunotherapy offers a promising avenue in management of many gastrointestinal malignancies specifically in treatment of gastroesophageal cancers and hepatocellular carcinoma [13]. In addition, ICIs can be used in patients with chemotherapy-resistant tumors through tissue agnostic approval for MSI-H and high mutational burden tumors [14]. ICIs have shown that they are not only efficacious but have superior safety profile as well [15].…”