Baseline mutational profiles of patients (pts) with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO
AuthorsWestphalen, C. B.
AffiliationComprehensive Cancer Center Munich & Department of Medicine III, Ludwig Maximilian University of Munich, Munich, Germany
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AbstractBackground NCCN guidelines consider next-generation sequencing important in guiding therapeutic decision-making in CUP. CUPISCO (NCT03498521) is an ongoing, phase II randomised study of targeted therapy/cancer immunotherapy vs platinum-based chemotherapy in pts with unfavourable CUP, defined per ESMO guidelines. We present a preliminary, descriptive molecular analysis of ?50% of pts designated for enrolment. Methods Upon enrolment, comprehensive genomic profiling, including determination of microsatellite instability and tumour mutational burden (TMB), was performed on formalin-fixed, paraffin-embedded tissues using the F1CDx assay. Gene alterations (GAs) found in ?3% of pts were analysed using multiple correspondence analyses and hierarchical clustering to identify co-occurrences. Results Median age was 61.5 years (n = 346 [Apr 2021]; range: 22�84); median TMB was 2.5 mutations/Mb (0�63.0). In our analysis, 30% of patients carried a potentially targetable GA. Most frequent GAs were TP53 (44%), CDKN2A (32%), KRAS (21%; 2% G12C alterations), CDKN2B (21%), ARID1A (13%), STK11 (13%), MTAP (12%), PIK3CA (10%), MYC (8%), PBRM1 (8%), BAP1 (8%) and FGFR2 (8%). Beyond PIK3CA and FGFR2, other targetable GAs were identified in EGFR (2%), ERBB2 (6%), ALK (0.3%), ROS1 (1%), MET (2%), NTRK1 (1%) and BRAF (6%). The frequency of microsatellite instability and TMB-high (>16 mutations/Mb) samples was 3% and 9%, respectively. Based on hierarchical clustering of co-mutational profiles, multiple clusters were identified in the study cohort, each characterised by specific GA co-occurrences. Conclusions This descriptive analysis sheds further light on the molecular landscape in pts with poor-prognosis CUP. Our analyses demonstrate that CUP cases can be clustered based on molecular profiling; further studies are needed to determine if these clusters carry clinical relevance. Our early results suggest that comprehensive genomic profiling of CUP samples identifies therapeutically relevant GAs in a significant proportion of patients and could thus guide personalised treatment of these tumours.
CitationWestphalen CB, Karapetyan A, Beringer A, Bochtler T, Chalabi N, Cook N, et al. 1804P Baseline mutational profiles of patients (pts) with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO. Vol. 32, Annals of Oncology. Elsevier BV; 2021. p. S1227�8.
JournalAnnals of Oncology