Impact of first-line (1L) therapy on outcomes of adult patients (pts) with metastatic MiT family translocation renal cell carcinomas (TRCC) treated in the contemporary immune checkpoint therapy (ICT) era

TRCC represent a rare and aggressive subgroup of RCC. While 1L therapy recommendations and clinical prognostication of pts with clear-cell RCC are well-known, data on TRCC clinical behavior are limited. TRCC is reported to be an immune cold tumor and the data surrounding 1L ICT is scarce. This is an international, multicenter, retrospective study of adult pts with metastatic TRCC treated with systemic therapies at centers in France, Belgium and in the US. The main objective was to identify prognostic factors associated with 1L therapy and to estimate overall survival (OS). Fifty-six pts with metastatic TRCC treated at 11 participating centers were evaluable. Median age was 38 years (range 16-62). IMDC risk group was favorable (9/56; 16%), intermediate (38/56; 68%), poor (8/56; 14%) and unknown for 1 patient. Twenty-nine pts (52%) presented with metastatic disease at initial diagnosis; 42 pts (75%) had prior nephrectomy (Nx). 1L therapy included VEGFR tyrosine kinase inhibitors (TKI), ICT combinations (either with TKI or ICT), or other regimens in 32 (57.1%), 18 (32.2%) and 6 pts (10.7%), respectively. With a median follow-up of 27.8 months, 30 pts died from disease progression; median OS was 13.5 months (mo) (95% CI: 3.9-NA) for pts treated with ICT combinations in 1L versus 36.2 mo (95% CI: 27.7-NA) for others (p=0.001). By univariable analysis, ICT combinations in 1L [HR: 3.8; 95% CI (1.6-8.9), p=0.002] and poor risk IMDC group [HR:4.2; 95%CI (1.25-14); p=0.02] were associated with worse OS, while prior Nx was associated with better OS [HR: 0.35; 95% CI (0.16-0.78); p=0.01]. By multivariable analysis, 1L ICT combinations [HR: 3.6; 95% CI (1.4-9.5); p=0.009] and IMDC poor risk group [HR: 4.6; 95%CI (1.05-19.9); p=0.04] were retained as independent variables associated with inferior OS. These data suggest that some TRCC patients might not derive benefit from a 1L ICT combinations and highlight the variability of this rare subtype of RCC compared to clear-cell RCC. Further collaborative research efforts are needed to elucidate the biology underpinning these findings and to develop more effective therapies for TRCC.