Supplementary Methods from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers

Horak, Peter; Heining, Christoph; Kreutzfeldt, Simon; Hutter, Barbara; Mock, Andreas; Hüllein, Jennifer; Fröhlich, Martina; Uhrig, Sebastian; Jahn, Arne; Rump, Andreas; Gieldon, Laura; Möhrmann, Lino; Hanf, Dorothea; Teleanu, Veronica; Heilig, Christoph E.; Lipka, Daniel B.; Allgäuer, Michael; Ruhnke, Leo; Laßmann, Andreas; Endris, Volker; Neumann, Olaf; Penzel, Roland; Beck, Katja; Richter, Daniela; Winter, Ulrike; Wolf, Stephan; Pfütze, Katrin; Geörg, Christina; Meißburger, Bettina; Buchhalter, Ivo; Augustin, Marinela; Aulitzky, Walter E.; Hohenberger, Peter; Kroiss, Matthias; Schirmacher, Peter; Schlenk, Richard F.; Keilholz, Ulrich; Klauschen, Frederick; Folprecht, Gunnar; Bauer, Sebastian; Siveke, Jens Thomas; Brandts, Christian H.; Kindler, Thomas; Boerries, Melanie; Illert, Anna L.; von Bubnoff, Nikolas; Jost, Philipp J.; Spiekermann, Karsten; Bitzer, Michael; Schulze-Osthoff, Klaus; von Kalle, Christof; Klink, Barbara; Brors, Benedikt; Stenzinger, Albrecht; Schröck, Evelin; Hübschmann, Daniel; Weichert, Wilko; Glimm, Hanno; Fröhling, Stefan

doi:10.1158/2159-8290.22540591.v1

Supplementary Methods from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers

journal contribution

posted on 2023-04-03, 23:43 authored by Peter Horak, Christoph Heining, Simon Kreutzfeldt, Barbara Hutter, Andreas Mock, Jennifer Hüllein, Martina Fröhlich, Sebastian Uhrig, Arne Jahn, Andreas Rump, Laura Gieldon, Lino Möhrmann, Dorothea Hanf, Veronica Teleanu, Christoph E. Heilig, Daniel B. Lipka, Michael Allgäuer, Leo Ruhnke, Andreas Laßmann, Volker Endris, Olaf Neumann, Roland Penzel, Katja Beck, Daniela Richter, Ulrike Winter, Stephan Wolf, Katrin Pfütze, Christina Geörg, Bettina Meißburger, Ivo Buchhalter, Marinela Augustin, Walter E. Aulitzky, Peter Hohenberger, Matthias Kroiss, Peter Schirmacher, Richard F. Schlenk, Ulrich Keilholz, Frederick Klauschen, Gunnar Folprecht, Sebastian Bauer, Jens Thomas Siveke, Christian H. Brandts, Thomas Kindler, Melanie Boerries, Anna L. Illert, Nikolas von Bubnoff, Philipp J. Jost, Karsten Spiekermann, Michael Bitzer, Klaus Schulze-Osthoff, Christof von Kalle, Barbara Klink, Benedikt Brors, Albrecht Stenzinger, Evelin Schröck, Daniel Hübschmann, Wilko Weichert, Hanno Glimm, Stefan Fröhling

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ARTICLE ABSTRACT

The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population. Rare cancers are difficult to treat; in particular, molecular pathogenesis–oriented medical therapies are often lacking. This study shows that whole-genome/exome and RNA sequencing enables molecularly informed treatments that lead to clinical benefit in a substantial proportion of patients with advanced rare cancers and paves the way for future clinical trials.See related commentary by Eggermont et al., p. 2677.This article is highlighted in the In This Issue feature, p. 2659