The prognostic impact of the metastatic pattern in advanced Renal Cell Carcinoma (aRCC): a retrospective analysis of 306 patients (pts) treated with compassionate ipilimumab and nivolumab (IPI+NIVO)
Gandini 1, A. Signori 2, S.E. Rebuzzi 3, G. Tortora 4, L. Galli 5, C. Porta 6, U. De Giorgi 7, S. Bracarda 8, F. Atzori 9, G. Procopio 10, L. Fratino 11, G.L. Banna 12, V. Conteduca 13, P. Rescigno 14, U. Basso 15
(1) Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino of Genova, Genova, Italy. – Italy, (2) Department of Health Sciences, Section of Biostatistics, University of Genova, Genoa, Italy. – Italy, (3) Medical Oncology Unit, Ospedale San Paolo, Savona, Italy. – Italy, (4) Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. – Italy, (5) Medical Oncology Unit 2, Santa Chiara Hospital, Azienda Ospedaliero-Universitaria Pisana, 56124 Pisa, Italy. – Italy, (6) Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy. – Italy, (7) Department of Medical Oncology, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) “Dino Amadori”, Meldola, Italy. – Italy, (8) Azienda Ospedaliera Santa Maria of Terni, Terni, Italy. – Italy, (9) Medical Oncology Department, University Hospital, University of Cagliari, Cagliari, Italy. – Italy, (10) SS Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, Italy. – Italy, (11) Medical Oncology, Centro di Riferimento Oncologico di Aviano, National Cancer Institute, Aviano, Italy. – Italy, (12) Portsmouth Hospitals University NHS Trust, Portsmouth, P06 3LY, UK. – United Kingdom, (13) University of Foggia, Policlinico Riuniti, Foggia, Italy. – Italy, (14) Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, UK. – United Kingdom, (15) IOV – IRCCS, Oncologia 1, Istituto Oncologico Veneto, Padova, Italy. – Italy
Objective:
The combination of IPI+NIVO is a first line option for IMDC intermediate-poor risk disease aRCC. Factors for risk stratification and pts selection remain, however, unmet clinical need. We assessed the different prognostic impact of pattern of metastases in aRCC that could be potential biomarker for IPI+NIVO treatment choice.
Methods:
aRCC who received IPI+NIVO among the Expanded Access Program available in Italy between April and October 2019 were included in the analysis. Clinical data were retrospectively collected. Statistical analyses were conducted with Software Stata 16. Univariable (UNV) and Multivariable (MLV) Cox regression analyses were conducted.
Results:
Among 86 Italian centers, 306 pts with aRCC were included. Pts were mostly males (74%), with a median age of 62 and prevalent clear cell tumor histology (86%). The most frequent sites of metastases (mts) were lung (70%), bone (31%), liver (18%), brain (8%) and pancreas (5%). One-year Overall Survival (OS) was 67%. Half of the pts had only 1 mts site, 26% had 2 mts sites and 9% had ≥ 3 mts sites. A higher number of mts sites directly correlated with worse OS. In MLV analysis, the prognostic factors associated with worse OS were poor IMDC (HR 2.94; p<0.001), non-clear cells histology (HR 2.20; p=0.001), brain mts (HR 1.96; p=0.033) and the presence of both lung and bone mts (HR 2.11; p=0.026). In terms of risk of progression, the presence of bone and liver mts together appeared the most impactful factor (HR 3.12; p<0.001).
Conclusions:
Our findings confirm that brain and bone mts, alone or in combination, may negatively affect OS in aRCC treated with first line IPI+NIVO. Despite the known favorable prognostic factor of lung mts alone, when associated with bone mts they unfavorably impact on OS. Number of mts and the type of mts sites should be considered in the risk stratification of aRCC pts.