Can pediatric and adolescent patients with recurrent tumors benefit from a precision medicine program? The European MAPPYACTS experience.

person Pablo Berlanga Gustave Roussy Cancer Campus, Villejuif, France info_outline Pablo Berlanga, Gaëlle Pierron, Ludovic Lacroix, Tiphaine Adam de Beaumais, Virginie Bernard, Sophie Cotteret, Nicolas Andre, Nadege Corradini, Estelle Thebaud, Samuel Abbou, Michela Casanova, Cormac Owens, Stefan Michiels, Olivier Delattre, Gilles Vassal, Gudrun Schleiermacher, Birgit Geoerger

Authors person Pablo Berlanga Gustave Roussy Cancer Campus, Villejuif, France info_outline Pablo Berlanga, Gaëlle Pierron, Ludovic Lacroix, Tiphaine Adam de Beaumais, Virginie Bernard, Sophie Cotteret, Nicolas Andre, Nadege Corradini, Estelle Thebaud, Samuel Abbou, Michela Casanova, Cormac Owens, Stefan Michiels, Olivier Delattre, Gilles Vassal, Gudrun Schleiermacher, Birgit Geoerger Organizations Gustave Roussy Cancer Campus, Villejuif, France, Institut Curie, Paris, France, Children’s Hospital of La Timone, AP-HM, Aix Marseille University, Marseille, France, Institut d'Hematologie et d'Oncologie Pédiatrique, Lyon, France, CHU Nantes-Hôpital Mère-Enfant, Nantes, France, Institut Gustave Roussy, Villejuif, France, Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy, Pediatric Haematology/Oncology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland, Institut Gustave Roussy, Paris, France, Department of Pediatric Oncology and INSERM U830, Institut Curie, Paris, France Abstract Disclosures Research Funding Other Foundation Background: The international prospective precision medicine trial MAPPYACTS (NCT02613962) aims to define the molecular profile in recurrent/refractory malignancies in order to suggest the most adapted salvage treatment. Methods: Patients < 18 years-old at the time of initial diagnosis underwent on-purpose tumor biopsy/surgery of their recurrent/refractory malignancy for molecular characterization by WES and whole RNA sequencing. Results were reviewed in a dedicated weekly molecular tumor board (MTB), followed by discussion with the treating physician in a clinical MTB (CMTB). Whenever possible, patients were enrolled subsequently in clinical trials based on CMTB recommendations. Results: From February 2016 to October 2018, 500 patients have been included in 17 centers in France, Italy and Ireland. Median age at inclusion was 13 years. 38% had sarcomas, 28% brain tumors, 22% other solid tumors, 12% hematological malignancies with a median of one prior relapse/progression. Eleven patients did not undergo intervention procedure (10 screening failures, 1 consent withdrawal). Molecular profiling was performed on samples in 433 patients and was contributive for 390 patients. For 271/390 patients (70%), there was at least one genetic alteration that could represent a potential therapeutic target and 8% had alterations considered as “ready for use” for treatment at relapse. Among them, 19 (7%) died before the CMTB. With follow-up censored in January 2019, 72 patients (27%) were treated with at least one matched targeted agent, 57 of them in a clinical trial, mostly the proof-of concept AcSé-ESMART trial (NCT02813135). Of the 166 patients (61%) that did not receive the matched treatment recommended by CMTB (80 still on follow-up), main reasons were: response/stable disease under previous therapy (50), another treatment (48), rapid disease progression/death (30) and legal representative refusal (12). Conclusions: MAPPYACTS profiling allowed tailored targeted treatment, mainly through early clinical trials, in patients with recurrent pediatric cancer. Since most detected molecular findings are within the investigational or hypothetical evidence level, therapeutic proof-of-concept trials that are exploring targeted therapies in molecularly enriched patient populations are crucial to improve knowledge and potentially outcome. Clinical trial information: NCT02613962