Baseline mutational profiles of patients with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO
Mileshkin, L. Karapetyan, A. R. Beringer, A. Bochtler, T. Chalabi, N. Duran-Pacheco, G. Golding, S. Hoglander, E. Losa, F.
Mileshkin, L.
Karapetyan, A. R.
Beringer, A.
Bochtler, T.
Chalabi, N.
Duran-Pacheco, G.
Golding, S.
Hoglander, E.
Losa, F.
Citations
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Abstract
Aims: NCCN guidelines consider next-generation sequencing important in therapeutic decision-making in CUP. CUPISCO (NCT03498521) is an ongoing, phase II, randomized study of targeted therapy/cancer immunotherapy vs platinum-based chemotherapy in ESMO-guideline-defined unfavourable CUP. We present a preliminary, descriptive molecular analysis of ∼50% of patients designated for enrollment. Methods: Upon enrollment, comprehensive genomic profiling, including determination of microsatellite instability and tumour mutational burden (TMB), was performed on formalin-fixed, paraffin-embedded issues using the F1CDx assay. Gene alterations (GAs) found in ≥3%
of patients were analyzed 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, 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 characterized by specific GA cooccurrences.
Conclusions: This descriptive analysis sheds further light on the molecular landscape in patients 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 personalized treatment of these tumors.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Mileshkin L, Karapetyan AR, Beringer A, Bochtler T, Chalabi N, Cook N, et al. Baseline mutational profiles of patients with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO. Asia-Pacific Journal of Clinical Oncology. 2021;17:129-30.