Abstract 98P
Background
Cancer of Unknown Primary (CUP) poses a significant challenge due to poor clinical outcomes and limited treatment options. As such, further definition of clinicopathological factors and genomic profile to better adapt treatment strategies is required.
Methods
Medical records were interrogated to retrospectively include CUP with available clinical and genomics data at the European Institute of Oncology. Next-generation sequencing (NGS) included targeted panels. Statistical analyses were conducted with R Software 4.2.2.
Results
A total of 44 patients were included. With a median follow-up of 14.1 months, median PFS (mPFS) to first-line regimen was 3.98 months (95% confidence interval [CI] 2.5-5.98), with a clinical benefit rate of 26% (95%CI 14-49%). Most patients (23 of 31, 74.19%) received platinum-doublet chemotherapy, with no statistically significant difference between first-line chemotherapy regimens. Median OS (mOS) was 18.8 months (95%CI 12.3-39.9), with a 12-month OS rate of 66% (95%CI 50-85%). Male sex (HR 11.8 [95%CI 2.04-68.06], P=0.005) and number of metastatic sites (≥2 vs <2) (HR 5.46 [95%CI 1.02-29.30], P=0.04) independently associated with OS in the multivariable model. For 11 patients NGS failed. For the remaining, TP53 (n=16, 48%) and KRAS (n=10, 30%) represented the most altered (alt) genes, with no prognostic impact for both genomic alterations. No microsatellite instability was observed (0 of 28), while 6 of 28 (21.43%) tumors carried high TMB (≥10 mutation per megabase). Seven of 33 tumors (21.2%) displayed at least one actionable alteration with potential clinical benefit according to ESCAT. Only two of them received targeted therapy matched to genomic alterations, with a combined mPFS of 2.63 months (95%CI 1.84-NA) as third-line regimens. Six patients received anti-PD1/PD-L1 therapy, showing a meaningful mPFS of 13 months (95%CI 2.04-NA).
Conclusions
CUP exhibit poor prognosis with limited benefits from standard treatment regimens. A significant proportion of CUPs carry actionable alterations, underscoring the importance of genomic profiling to gather additional treatment opportunities. Lastly, immunotherapy might represent a valuable treatment option for a subset of CUP.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
L. Boscolo Bielo.
Funding
Has not received any funding.
Disclosure
M. Repetto: Other, Personal, Other, Travel expenses: Sanofi. E. Guerini Rocco: Financial Interests, Personal, Advisory Role: AstraZeneca, GSK, Roche, Thermo Fisher; Financial Interests, Personal, Advisory Board: Novartis. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Advisory Board, Advisory Board: Menarini, Gilead; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I Clinical Basket Trial: Relay Therapeutics; Non-Financial Interests, Personal, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Personal, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Personal, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Personal, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Personal, Officer, ESMO Clinical Practice Guidelines Chair: ESMO; Non-Financial Interests, Personal, Member of Board of Directors, Chair of Clinical Practice Guidelines Committee: ESMO. All other authors have declared no conflicts of interest.