Assessing the clinical benefit from medical therapies in CNS malignancies: Refining the ESMO Magnitude of Clinical Benefit Scale and the ASCO Value Framework.

Background: An objective assessment of patient-centered clinical benefit derived from an anticancer therapy weighs clinical and radiographic outcome against treatment-related burden. Both, the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) have developed assessment tools to guide such evaluations. These tools, however, have not been validated for application to neuro-oncology studies. Methods: We applied the ESMO-Magnitude of Clinical Benefit (ESMO-MCBS) v1.1. and ASCO net health benefit v2 scales to 16 neuro-oncological studies. We developed the Neuro-Oncology Magnitude of Clinical Benefit (Neuro-MCBS) scale and tested its application in select patient cohorts of MTB@ZPM (NCT03503149), a longitudinal observational study that provides comprehensive molecular profiling, consensus-guided and ranked targeted therapy recommendations and prospective assessment of clinical outcome. Results: Of 10 randomized phase 3 clinical trials and 6 single-arm clinical studies, 9 and 5 were scoreable by ESMO-MCBS v1.1, respectively. A score of 4 was achieved by 5 of the phase 3 and one of the single-arm studies, signifying clinical benefit. Application to these neuro-oncology studies was limited by high variability in criteria used to assess treatment response and lack of credit to therapies that lead to disease control. Based hereon, we developed the Neuro-MCBS suitable to specific needs of neuro-oncology studies and found it to be practicable and applicable to these landmark neuro-oncology studies and various treatment cohorts in MTB@ZPM. Conclusions: The Neuro-MCBS is a comprehensive, clinically relevant tool and particularly suitable to assess the clinical benefit derived from novel antitumor therapies in neuro-oncology studies.