TY - JOUR
T1 - Limited evolution of the actionable metastatic cancer genome under therapeutic pressure
AU - van de Haar, Joris
AU - Hoes, Louisa
AU - Roepman, Paul
AU - Lolkema, Martijn P.
AU - Verheul, Henk M. W.
AU - Gelderblom, Hans
AU - de Langen, Adrianus J.
AU - Smit, Egbert F.
AU - Cuppen, Edwin
AU - Wessels, Lodewyk F.A.
AU - Voest, Emile E.
PY - 2021
Y1 - 2021
N2 - Genomic profiling is critical for the identification of treatment options for patients with metastatic cancer, but it remains unclear how frequently this procedure should be repeated during the course of the disease. To address this, we analyzed whole-genome sequencing (WGS) data of 250 biopsy pairs, longitudinally collected over the treatment course of 231 adult patients with a representative variety of metastatic solid malignancies. Within the biopsy interval (median, 6.4 months), patients received one or multiple lines of (mostly) standard-of-care (SOC) treatments, with all major treatment modalities being broadly represented. SOC biomarkers and biomarkers for clinical trial enrollment could be identified in 23% and 72% of biopsies, respectively. For SOC genomic biomarkers, we observed full concordance between the first and the second biopsy in 99% of pairs. Of the 219 biomarkers for clinical trial enrollment that were identified in the first biopsies, we recovered 94% in the follow-up biopsies. Furthermore, a second WGS analysis did not identify additional biomarkers for clinical trial enrollment in 91% of patients. More-frequent genomic evolution was observed when considering specific genes targeted by small-molecule inhibitors or hormonal therapies (21% and 22% of cases, respectively). Together, our data demonstrate that there is limited evolution of the actionable genome of treated metastases. A single WGS analysis of a metastatic biopsy is generally sufficient to identify SOC genomic biomarkers and to identify investigational treatment opportunities.
AB - Genomic profiling is critical for the identification of treatment options for patients with metastatic cancer, but it remains unclear how frequently this procedure should be repeated during the course of the disease. To address this, we analyzed whole-genome sequencing (WGS) data of 250 biopsy pairs, longitudinally collected over the treatment course of 231 adult patients with a representative variety of metastatic solid malignancies. Within the biopsy interval (median, 6.4 months), patients received one or multiple lines of (mostly) standard-of-care (SOC) treatments, with all major treatment modalities being broadly represented. SOC biomarkers and biomarkers for clinical trial enrollment could be identified in 23% and 72% of biopsies, respectively. For SOC genomic biomarkers, we observed full concordance between the first and the second biopsy in 99% of pairs. Of the 219 biomarkers for clinical trial enrollment that were identified in the first biopsies, we recovered 94% in the follow-up biopsies. Furthermore, a second WGS analysis did not identify additional biomarkers for clinical trial enrollment in 91% of patients. More-frequent genomic evolution was observed when considering specific genes targeted by small-molecule inhibitors or hormonal therapies (21% and 22% of cases, respectively). Together, our data demonstrate that there is limited evolution of the actionable genome of treated metastases. A single WGS analysis of a metastatic biopsy is generally sufficient to identify SOC genomic biomarkers and to identify investigational treatment opportunities.
UR - http://www.scopus.com/inward/record.url?scp=85112662777&partnerID=8YFLogxK
U2 - 10.1038/s41591-021-01448-w
DO - 10.1038/s41591-021-01448-w
M3 - Article
C2 - 34373653
AN - SCOPUS:85112662777
SN - 1078-8956
VL - 27
SP - 1553
EP - 1563
JO - Nature Medicine
JF - Nature Medicine
IS - 9
ER -