Please keep in mind that this provisional clinical opinion, which also includes such future trends, will be revised in a timely manner, along with continuously and steadily advancing cancer treatment and new knowledge on biomarkers, including dMMR. However, these testing methods are expected to shift to next-generation sequencing (NGS) in the near future. In Europe and the US, MSI testing and mismatch repair protein immunostaining are the most common dMMR-testing methods. It is highly recommended that immune checkpoint inhibitors are used in an environment, where adequate measures can be taken in response to immune-related adverse events. It is highly recommended to carry out dMMR testing in an environment with established genetic diagnostic and genetic counseling systems. It is highly recommended to carry out dMMR testing in an environment that can ensure technical accuracy and the quality of the results. When a tumor is detected in patients already diagnosed with Lynch syndrome, dMMR testing for determining eligibility for PD-1/PD-L1 inhibitors is recommended.Īs dMMR testing for determining eligibility PD-1/PD-L1 inhibitors, microsatellite instability (MSI) testing is highly recommended.Īs dMMR testing for determining eligibility for PD-1/PD-L1 inhibitors, immunohistochemistry (IHC) is recommended.Īs dMMR testing for determining eligibility for PD-1/PD-L1 inhibitors, an NGS testing approach for which analytical validity has been established is recommended. This provisional clinical opinion proposes the following 11 requirements regarding the dMMR testing performed to select patients who are likely to benefit from PD-1/PD-L1 inhibitors.įor patients with solid tumors who are receiving standard systemic treatment or who have difficulty receiving any standard treatment, dMMR testing is highly recommended to determine eligibility for PD-1/PD-L1 inhibitors.įor patients with unresectable solid tumors, irrespective of MMR status, for which clinical application of PD-1/PD-L1 inhibitors has already been approved, dMMR testing should be considered to determine eligibility for PD-1/PD-L1 inhibitors.įor patients with solid tumors that are curable with local treatment, dMMR testing for determining eligibility for PD-1/PD-L1 inhibitors is not recommended.įor patients with solid tumors who have already undergone treatment with PD-1/PD-L1 inhibitors, dMMR testing for redetermining eligibility for PD-1/PD-L1 inhibitors is not recommended. This has made it necessary to develop reference manuals, including guidelines, which enable smooth implementation of testing and treatment in the clinical setting. In Japan, PD-1 inhibitor for advanced/recurrent microsatellite instability-high (MSI-H) solid tumors, regardless of the primary tumor site, has been approved. In recent years, many clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of advanced solid tumors with deficient DNA mismatch repair (dMMR).
This provisional clinical opinion proposes the requirements for performing dMMR testing properly to select patients who are likely to benefit from immune checkpoint inhibitors and administering them safely. The current guideline, which we consider a provisional clinical opinion at this point, describes the 11 requirements to be considered in terms of patients for whom dMMR testing is recommended, the timing and methods of dMMR testing, and clinical care systems required to perform dMMR testing properly and to administer immune checkpoint inhibitors safely. Then, the committee members voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other factors.
#Keynote 158 manual
MethodsĬlinical questions (CQs) regarding medical care were formulated for patients with dMMR advanced solid tumors, and evidence to the CQs was collected by manual search to prepare recommendations. However, there are some issues related to administering immune checkpoint inhibitors in the clinical practice setting, making it necessary to develop the guidelines. In Japan, a PD-1 inhibitor for dMMR advanced solid tumors, regardless of the primary tumor site, has been approved. Recently, clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. In parallel, the development of predictive biomarkers to identify patients who are likely to benefit from a certain treatment has also contributed to the improvement of survival. Novel therapeutic agents have improved survival outcomes in patients with advanced solid tumors.
0 kommentar(er)
