Unfavourable carcinoma of unknown primary (CUP) with gastrointestinal profile: A retrospective study.

person Lorenzo Guidi Istituto Europeo di Oncologia IRCCS, Milano, Italy info_outline Lorenzo Guidi, Carmine Valenza, Elena Battaiotto, Luca Boscolo Bielo, Edoardo Crimini, Carmen Belli, Lorenzo Gervaso, Chiara Alessandra Cella, Davide Ciardiello, Konstantinos Venetis, Luca Bottiglieri, Mariacristina Ghioni, Elena Guerini Rocco, Nicola Fazio, Maria Giulia Zampino, Giuseppe Curigliano

Authors person Lorenzo Guidi Istituto Europeo di Oncologia IRCCS, Milano, Italy info_outline Lorenzo Guidi, Carmine Valenza, Elena Battaiotto, Luca Boscolo Bielo, Edoardo Crimini, Carmen Belli, Lorenzo Gervaso, Chiara Alessandra Cella, Davide Ciardiello, Konstantinos Venetis, Luca Bottiglieri, Mariacristina Ghioni, Elena Guerini Rocco, Nicola Fazio, Maria Giulia Zampino, Giuseppe Curigliano Organizations Istituto Europeo di Oncologia IRCCS, Milano, Italy, Division of Early Drug Development, European Institute of Oncology IRCCS, University of Milan, Milan, Italy, European Institute of Oncology (IEO), Milan, NA, Italy, European Institute Of Oncology, IRCCS, University of Milan, Milano, Italy, European Institute Of Oncology, IRCCS, University of Milan, Milan, Italy, Istituto Europeo Oncologico, Milano, Italy, European Institute of Oncology (IEO) IRCCS, Milan, Italy, Istituto Europeo Oncologico, Milano, MI, Italy, Division of Pathology, IEO, European Institute of Oncology, IRCCS, and Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy, European Institute of Oncology, IEO, IRCCS, Milan, Italy, Medical Oncology Deparment, Istituto Europeo di Oncologia – IRCCS, Milan, Italy, University of Milan and European Institute of Oncology, IRCCS, Milan, Italy Abstract Disclosures Research Funding No funding sources reported Background: According to European Society of Medical Oncology (ESMO) guidelines, CUP are classified in favorable and unfavorable subsets. Favorable CUPs (20% of pts) have clinical aspects and either pathology highly suggestive for specific site of origin or with amenable metastases for localized treatment with curative intent; they are treated with site-specific chemotherapy (CT). All other CUPs (80%) are defined unfavorable and are treated with empiric CT regimens. There is no data about the best CT regimen for unfavourable CUPs with GI profile, i.e., those CUPs that do not meet the criteria of favourable colon-like CUP (CK7-/CK20+/CDX2+) but have a morphological/immunohistochemical profile suggestive for the digestive system. Methods: We conducted a single-center retrospective study to describe outcomes and prognostic factors of pts with unfavourable CUPs with GI profile, referred to our center from Jan 2000 to Aug 2023, who received at least one cycle of first-line CT. The definition of GI profile was: a) negativity for GATA-3, PAX-8 and TTF-1 and b) CK7+/CK20-/anyCDX2 or CK7-/CK20+/CDX2- or CK7-/CK20-/CDX2+, or c) presence of an abundant mucinous component and/or a signet ring cell component. The primary endpoint was the progression free survival (PFS) of first line chemotherapy for advanced disease. Results: 43 pts were included (characteristics in table). After a median follow-up of 43.9 months, 33 deaths were registered and the mOS was 12.6 months (95% CI, 8.7-16.5). Forty PFS events were registered and the mPFS was 6.1 months (95% CI, 3.5-8.9). At univariate analysis, male pts (p=0.034), peritoneal metastases (p=0.0282), residual tumor after surgery (p=0.002), suspected biliopancreatic origin (p=0.033), PS ECOG > 1 (p<0.001) and CDX2- status (p=0.025) were associated with shorter PFS. No CT regimen was superior in terms of PFS at both univariate (p=0.282) and multivariable analysis after adjusting for peritoneal metastases, suspected origin, gender and baseline ECOG PS. Conclusions: Although limited by the small sample size, this study showed that all CT regimens were comparable in terms of PFS among patients with unfavorable CUP with gastrointestinal profile. Keywords (3/10): cancer of unknown primary; peritoneal metastases; chemotherapy. N=43 Male, n (%) 12 (29%) ECOG Performance Status (PS) 0-1, n (%) 41 (95%) Visceral disease at baseline, n (%) 37 (86%) Peritoneal disease at baseline, n (%) 20 (46%) >1 metastatic site, n (%) 34 (79%) No residual tumor after surgery, n (%) 12 (28%) Suspected origin - Upper GI | Lower GI | Biliopancreatic, n (%) 10 (23%) | 13 (43%) | 20 (46%) CDX2 status +| - | NA, n (%) 17 (40%) | 13 (30%) | 13 (30%) Regimen – Platinum+5FU | Platinum+taxane | Platinum+Gemcitabine | Other, n (%) 16 (37 %) | 7 (16%) | 13 (30%) | 7 (16%) GI: gastrointestinal; 5FU: 5Fluorouracil; NA: Not Assessed.