Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition

Abstract

Background Novel therapeutic agents have improved survival outcomes in patients with 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. Recently, clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. In Japan, a PD-1 inhibitor for dMMR advanced solid tumors, regardless of the primary tumor site, has been approved. However, there are some issues related to administering immune checkpoint inhibitors in the clinical practice setting, making it necessary to develop the guidelines. Methods Clinical 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. 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. Results 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. Conclusion 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.

Real‐world data on microsatellite instability status in various unresectable or metastatic solid tumors

“…Therefore, it is necessary to narrow down those patients expected to respond to ICIs. Currently, biomarkers to predict therapeutic response, such as PD-L1 expression, 1 MSI-H, or loss of mismatch repair protein expression [2][3][4] and tumor mutation burden-high 5 are used. Microsatellite instability-high results from dMMR.…”

Japan society of clinical oncology/Japanese society of medical oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese society of pediatric hematology/oncology

“…This article is a summary of the part describing NTRK in "Clinical Practice Guidelines for Tumor-Agnostic Treatments in Adult and Pediatric Patients with Advanced Solid Tumors toward Precision Medicine (in Japanese)". The part regarding dMMR has already been reported elsewhere [1].…”

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

“…Additionally, in the case of solid tumours for which the applicability of PD-1/PD-L1 inhibitors is judged appropriate based on a biomarker other than MSI/MMR status, such as PD-L1 expression, and that biomarker is negative, MSI/MMR testing is recommended, because these drugs are expected to be effective if the tumour is MSI/dMMR. 18 The general feeling of the experts was that the ideal scenario would be to test at the time of diagnosis and tissue availability, when there may be only one chance at biopsy. All the experts agreed with and accepted completely 'recommendation CQ2' [A¼100%].…”

“…Also, the Japan Society of Clinical Oncology (JSCO) published 'provisional clinical opinion' guidelines for the diagnosis and use of immunotherapy in patients with dMMR tumours, in July 2019. 18 In order to respond to the potential changes in clinical practice envisaged following the tumour-agnostic agent approvals described above, and those anticipated for other agents in the future, the JSCO convened a face-to-face meeting in Japan, in October 2019, of international experts in the field of oncology representing the oncology societies of Europe (ESMO), the United States (ASCO), and two additional Asian societies namely, the Japanese Society of Medical Oncology (JSMO) and the Taiwan Oncology Society (TOS). The ultimate aim of the meeting was to develop the present international expert consensus recommendations on tumour-agnostic therapies based on the results of expert voting on a series of preformulated recommendations focussing on patients with advanced (unresectable or metastatic) MSI/dMMR and NTRK fusion-positive solid tumours, as outlined below.…”