The Exceptional Responders Initiative: Feasibility of A National Cancer Institute Pilot Study

Menée à partir de l'examen approfondi de 476 patients atteints d'un cancer puis de l'analyse d'échantillons tumoraux et d'échantillons tissulaires normaux, cette étude évalue la possibilité d'identifier rétrospectivement des patients dont la réponse thérapeutique est exceptionnelle ainsi que des mutations constitutionnelles actionnables

Résumé en anglais

Tumor molecular profiling from patients experiencing exceptional responses to systemic therapy may provide insights into cancer biology and improve treatment tailoring. This pilot study evaluates the feasibility of identifying exceptional responders retrospectively, obtaining pre-exceptional response treatment tumor tissues, and analyzing them with state-of-the-art molecular analysis tools to identify potential molecular explanations for responses.Exceptional response was defined as partial (PR) or complete (CR) response to a systemic treatment with population PR or CR rate < 10%, or an unusually long response (e.g. duration > 3 times published median). Cases proposed by patients’ clinicians were reviewed by clinical and translational experts. Tumor and normal tissue (if possible) were profiled with whole exome sequencing and, if possible, targeted deep sequencing, RNA sequencing, methylation arrays and immunohistochemistry (IHC). Potential germline mutations were tracked for relevance to disease.Cases reflected a variety of tumors and standard and investigational treatments. Of 520 cases, 476 (91.5%) were accepted for further review and 222/476 (46.6%) proposed cases met requirements as exceptional responders. Clinical data were obtained from 168/222 cases (75.7%). Tumor was provided from 130/168 cases (77.4%). Of 117/130 (90.0%) cases with sufficient nucleic acids, 109 (93.2%) were successfully analyzed; 6 patients had potentially actionable germline mutations.Exceptional responses occur with standard and investigational treatment. Retrospective identification of exceptional responders, accessioning and sequencing of pre- treatment archived tissue is feasible. Data from molecular analyses of tumors, particularly when combining results from patients who received similar treatments, may elucidate molecular bases for exceptional responses.