Authors: Mathilde Cancel, Jérémie Naffrichoux, Pierre Poupin, William Pouillot, Claude Linassier, Nathalie Rioux-Leclercq, Manon De Vries-Brilland, Loic Mourey, Brigitte Laguerre, Stephane Oudard, Marine Gross-Goupil, Gwenaelle Gravis, Frederic Rolland, Laura Moise, Sheik Muhummud Fardeen Emambux, Cecile Vassal, Sylvie Zanetta, Nicolas Penel, Laurence Albiges, Gaelle Fromont
Published: 2024-01-29
DOI: 10.1200/jco.2024.42.4_suppl.463
Source: Full article
463 Background: Papillary renal cell carcinoma (pRCC) is a rare and aggressive cancer with no specifically established therapeutic strategy in the metastatic setting. Combinations of tyrosine kinase and immune checkpoint inhibitors are a promising option. We aimed to study the immune landscape of metastatic pRCC, and its associations with angiogenesis pathways expressions, to search for potential therapeutic targets. Methods: The expression of immune markers (PD-L1, PD-1, PD-L2, LAG-3) and angiogenic pathways (CAIX, c-MET), was analyzed by immunohistochemistry on 75 metastatic pRCC retrieved from a retrospective multicenter GETUG cohort. Our primary endpoint was to evaluate the prognostic impact on overall survival (OS) of PD-L1 expression in metastatic pRCC. Secondary endpoints were to describe the expression of the other immune markers and of angiogenic pathways and to estimate the associations between the expression of PD-L1 and the expressions of the other markers or angiogenic pathways. Results: In median, patients were 61 years old at metastatic diagnosis. Concerning their first-line metastatic treatment, 67 (89%) had received Sunitinib, and 8 (11%) had received Everolimus. The Karnofsky Performance Score at treatment initiation was ≥ 80 for 62 (83%) patients. Overall, 25.3% of tumors were PD-L1 positive. PD-L2 was more frequently expressed (45.3%), PD-1 and LAG-3 were positive in 17.3% both. Concerning the angiogenic markers, CAIX was expressed in 46.7% of tumors, c-MET in 41.3%. None of these markers were significantly associated with PD-L1 expression. 64% (48/75) expressed at least one immune marker, and 40% (30/75) were “double-positive”, as they expressed both immune and angiogenic markers. In univariate analysis, OS was significantly shorter for patients with PD-L1 positive pRCC (HR=3.3; 95%CI=1.3-8.6; p=0.01). A multivariate analysis confirmed a significant association between PD-L1 expression and shorter survival (HR=5.4; 95%CI=1.4-20.9; p=0.01). Conclusions: These results reinforce clinical data on the expected benefit of immunotherapy in metastatic pRCC treatment, as PD-L1 expression is a factor of poor prognosis in our multicenter cohort.