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Baseline mutational profiles of patients (pts) with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO
Westphalen, C. B. Karapetyan, A. Beringer, A. Bochtler, T. Chalabi, N. Cook, Natalie Duran-Pacheco, G. Golding, S. Hoglander, E. Losa, F.
Westphalen, C. B.
Karapetyan, A.
Beringer, A.
Bochtler, T.
Chalabi, N.
Cook, Natalie
Duran-Pacheco, G.
Golding, S.
Hoglander, E.
Losa, F.
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Abstract
Background
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.
Description
Date
2021
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Citation
Westphalen 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.