Abstract 1804P
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.
Clinical trial identification
NCT03498521.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Stephen Salem, BSc, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
C.B. Westphalen: Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Other, Honoraria: Taiho; Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Shire/Baxalta; Financial Interests, Personal, Advisory Role: Rafael Pharmaceuticals; Financial Interests, Personal, Advisory Role: RedHill BioPharma; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accommodation expenses: Bayer; Financial Interests, Personal, Other, Travel/accommodation expenses: Celgene; Financial Interests, Personal, Other, Travel/accommodation expenses: RedHill BioPharma; Financial Interests, Personal, Other, Travel/accommodation expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accommodation expenses: Servier; Financial Interests, Personal, Other, Travel/accommodation expenses: Taiho; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. A. Karapetyan: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. A. Beringer: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. T. Bochtler: Financial Interests, Institutional, Research Grant, Institutional research funding: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Other, Works as study oncologist for the CUPISCO trial: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. N. Chalabi: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. N. Cook: Financial Interests, Personal and Institutional, Advisory Board: RedX Pharmaceuticals; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Research funding: AstraZeneca; Financial Interests, Institutional, Research Grant, Research funding: Orion; Financial Interests, Institutional, Research Grant, Research funding: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Research funding: Taiho; Financial Interests, Institutional, Research Grant, Research funding: GSK; Financial Interests, Institutional, Research Grant, Research funding: Novartis; Financial Interests, Institutional, Research Grant, Research funding: Starpharma; Financial Interests, Institutional, Research Grant, Research funding: Bayer; Financial Interests, Institutional, Research Grant, Research funding: Eisai; Financial Interests, Institutional, Research Grant, Research funding: UCB; Financial Interests, Institutional, Research Grant, Research funding: RedX Pharmaceuticals; Financial Interests, Institutional, Research Grant, Research funding: Stemline Therapeutics; Financial Interests, Institutional, Research Grant, Research funding: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, Research funding: Merck; Financial Interests, Institutional, Research Grant, Research funding: Tarveda Therapeutics. 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