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Abstract
Background
Trop-2 and Nectin-4 are transmembrane proteins overexpressed in many tumours and targets of antibody–drug conjugates (ADC). In metastatic colorectal cancer (mCRC), the role of Trop-2 and Nectin-4 has been poorly investigated.
Methods
Tumour samples of patients randomised in the phase III TRIBE2 were assessed for Trop-2 and Nectin-4 expression.
Results
Three hundred eighty-six tumours were assessed for Trop-2 expression. 90 (23%), 115 (30%) and 181 (47%) were Trop-2 high, medium and low, respectively. Patients with low Trop-2 tumours achieved longer PFS (12 versus 9.9 months, p = 0.047) and OS (27.3 versus 21.3 months, p = 0.015) than those with high/medium Trop-2 tumours. These findings were confirmed in multivariate analysis (p = 0.022 and p = 0.023, respectively). A greater OS benefit from treatment intensification with FOLFOXIRI/bevacizumab was observed in patients with high/medium Trop-2 tumours (p-for-interaction = 0.041).
Two hundred fifty-one tumours were assessed for Nectin-4 expression. Fourteen (5%), 67 (27%) and 170 (68%) were high, medium and low, respectively. No prognostic impact was observed based on Nectin-4 expression and no interaction effect was reported between Nectin-4 expression groups and treatment arm.
Conclusions
In mCRC, expression levels of Trop-2 and Nectin-4 are heterogeneous, suggesting a target-driven development of anti-Trop2 and anti-Nectin-4 ADCs. Medium/high Trop-2 expression is associated with worse prognosis and higher benefit from chemotherapy intensification.
Details
; Germani, Marco Maria 2 ; Giordano, Mirella 3 ; Conca, Veronica 2
; Proietti, Agnese 4 ; Niccoli, Cristina 4 ; Pietrantonio, Filippo 5
; Lonardi, Sara 6
; Tamburini, Emiliano 7 ; Zaniboni, Alberto 8 ; Passardi, Alessandro 9 ; Latiano, Tiziana Pia 10 ; Fanotto, Valentina 11 ; Di Donato, Samantha 12 ; Prisciandaro, Michele 5 ; Bergamo, Francesca 6 ; Masi, Gianluca 2 ; Fontanini, Gabriella 4 ; Ugolini, Clara 4 ; Cremolini, Chiara 2
1 Azienda Ospedaliero-Universitaria Pisana, Unit of Medical Oncology 2, Pisa, Italy (GRID:grid.144189.1) (ISNI:0000 0004 1756 8209)
2 Azienda Ospedaliero-Universitaria Pisana, Unit of Medical Oncology 2, Pisa, Italy (GRID:grid.144189.1) (ISNI:0000 0004 1756 8209); University of Pisa, Department of Translational Research and New Technology in Medicine and Surgery, Pisa, Italy (GRID:grid.5395.a) (ISNI:0000 0004 1757 3729)
3 University of Pisa, Department of Translational Research and New Technology in Medicine and Surgery, Pisa, Italy (GRID:grid.5395.a) (ISNI:0000 0004 1757 3729)
4 University of Pisa, Department of Surgical, Medical and Molecular Pathology and Critical Area, Pisa, Italy (GRID:grid.5395.a) (ISNI:0000 0004 1757 3729)
5 Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Medical Oncology, Milan, Italy (GRID:grid.417893.0) (ISNI:0000 0001 0807 2568)
6 Veneto Institute of Oncology—IRCCS, Medical Oncology Unit 3, Padua, Italy (GRID:grid.417893.0)
7 Ospedale degli Infermi, Oncology Unit, Rimini, Italy (GRID:grid.414614.2); Cardinale Panico Tricase City Hospital, Department of Oncology and Palliative Care, Tricase, Italy (GRID:grid.414614.2)
8 Poliambulanza Foundation, Medical Oncology Unit, Brescia, Italy (GRID:grid.415090.9) (ISNI:0000 0004 1763 5424)
9 IRCCS Istituto Romagnolo per Lo Studio Dei Tumori (IRST) “Dino Amadori”, Department of Medical Oncology, Meldola, Italy (GRID:grid.415090.9)
10 Casa Sollievo della Sofferenza, Oncology Unit, Foundation IRCCS, San Giovanni Rotondo, Italy (GRID:grid.413503.0) (ISNI:0000 0004 1757 9135)
11 ASUFC University Hospital of Udine, Department of Oncology, Udine, Italy (GRID:grid.411492.b)
12 Santo Stefano General Hospital, Department of Medical Oncology, Prato, Italy (GRID:grid.411492.b)