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.
| Original language | English |
|---|---|
| Journal | Cancer Discovery |
| Volume | 11 |
| Issue number | 11 |
| Pages (from-to) | 2780-2795 |
| Number of pages | 16 |
| ISSN | 2159-8274 |
| DOIs | |
| Publication status | Published - 11.2021 |
Funding
C. Heining reports personal fees from Roche and grants from Boehringer Ingelheim outside the submitted work. M. Fröhlich reports other support (family member is employed) by Merck. L. Möhrmann reports non-financial support from Celgene outside the submitted work. V. Endris reports personal fees from AstraZeneca, Novartis, Bayer, Lily, and Thermo Fisher outside the submitted work. M. Augustin reports personal fees from Novartis, Roche, Blueprint Medicines, Janssen-Cilag, Bristol-Myers Squibb, IPSEN, Pfizer, Merck, AstraZeneca, Bayer; grants from Bristol-Myers Squibb, IPSEN, Merck, MSD; Pfizer, AstraZeneca, Exelixis, PharmaMar, and grants from Morphosys outside the submitted work. W.E. Aulitzky reports other support from Astellas, Novartis, and Roche outside the submitted work. M. Kroiss reports grants from Deutsche Forschun-gsgemeinschaft during the conduct of the study; grants from Ipsen; other support from Lilly, Loxo Oncology; personal fees from Lilly, Bayer, Ipsen, MSD, and personal fees from BMS outside the submitted work. P. Schirmacher reports grants from Chugai; grants and personal fees from BMS, AstraZeneca, Roche, Incyte; personal fees from MSD, Janssen; grants from Sanofi Aventis, and grants and personal fees from Novartis outside the submitted work. U. Keilholz reports MerckSerono; grants and personal fees from MSD, AstraZeneca; personal fees from BMS, and personal fees from Pfizer outside the submitted work. F. Klauschen reports personal fees and other support from Aignostics GmbH; personal fees from BMS, Novartis, Roche, and personal fees from Agilent outside the submitted work. G. Folprecht reports grants from Merck-Serono GmbH; personal fees from Roche, Amgen, MSD, BMS, Servier, Bayer, and personal fees from Falk Foundation outside the submitted work. S. Bauer reports grants from Incyte, grants and personal fees from Blueprint Medicines, Novartis, and other support from Pfizer during the conduct of the study; grants from DFG (Deutsche Forschungsgemeinschaft); personal fees from Deciphera, Lilly, Daichii-Sankyo, Plexxikon, Exe-lixis, Bayer, PharmaMar, Roche, and personal fees from GSK outside the submitted work. J.T. Siveke reports grants and personal fees from BMS, Celgene; grants and personal fees from Roche; personal fees from AstraZeneca, Bayer, Baxalta, Immunocore, Lilly, Novartis, Shire; other support from FAPI Holding; and other support from Pharma15 outside the submitted work. A.L. Illert reports grants from German Cancer Aid and grants from German Society of Internal Medicine during the conduct of the study. N. von Bubnoff reports personal fees from Blueprint, Abbvie, Takeda, and personal fees from Novartis outside the submitted work. P.J. Jost reports grants and personal fees from Abbvie, Novartis; personal fees from Bayer, Boehringer, Pfizer, Servier, Roche, BMS/Celgene; personal fees and non-financial support from MSD, and nonfinancial support from Pierre Fabre outside the submitted work. M. Bitzer reports personal fees from Roche Pharma AG, Incyte Biosciences Germany GmbH, Bayer Vital GmbH, Bristol-Myers-Squibb GmbH & Co KGaA, and personal fees from MSD Sharp & Dohme GmbH outside the submitted work. A. Stenzinger reports grants and personal fees from Bayer, BMS; grants from Takeda, Incyte; personal fees from AstraZeneca, Eli Lilly, Illumina, MSD, Novartis, Janssen, Thermo Fisher, and personal fees from Pfizer during the conduct of the study. W. Weichert reports personal fees from Roche, MSD, BMS, AstraZeneca, Pfizer, Merck, Lilly, Boehringer, Novartis, Takeda, Bayer, Amgen, Astellas, Illumina, Siemens, Agilent, ADC, GSK, and Molecular Health, and grants from Roche, MSD, BMS, Roche, and AstraZeneca outside the submitted work. H. Glimm reports grants from German Cancer Foundation during the conduct of the study; grants from Bayer The authors thank Peter Lichter for helpful discussions; the NCT/ DKFZ Sample Processing Laboratory, the DKFZ Genomics and Proteomics Core Facility, and the DKFZ Omics IT and Data Management Core Facility for technical support; and Viktoria Brendel and Jana Viktoria Maier for administrative support. This work was supported by the NCT Molecular Diagnostics Program, grant H021 from the DKFZ-Heidelberg Center for Personalized Oncology, and the DKTK Joint Funding Program. outside the submitted work. S. Fröhling reports grants from German Cancer Consortium during the conduct of the study; personal fees from Amgen; grants from AstraZeneca, Pfizer; personal fees from Bayer, Eli Lilly, Illumina; grants and personal fees from PharmaMar, and grants and personal fees from Roche outside the submitted work. No disclosures were reported by the other authors.
Research Areas and Centers
- Centers: University Cancer Center Schleswig-Holstein (UCCSH)
