Dados do Trabalho

Título

BONE METASTASIS IS ASSOCIATED WITH LOWER SURVIVAL IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED WITH NIVOLUMAB AS SECOND-LINE TREATMENT AND BEYOND

Introdução

Immune checkpoint inhibitors (ICIs) defined a new era in the treatment of metastatic renal cell carcinoma (mRCC).
CheckMate-025 trial was the first to establish the effect of ICIs in the second-line therapy of mRCC. Despite being a standard of care now, little is known about predictors of response to immunotherapy in this population.

Objetivo

To characterize advanced renal cell carcinoma patients (pts) submitted to Nivolumab (Nivo) in second line and beyond (2L) in
our center. Secondarily, to identify prognostic factors for immunotherapy efficacy in this scenario.

Método

mRCC pts who underwent nivolumab in second or later lines in our center were retrospectively recruited. Data was retrieved from
medical records. Overall survival (OS) was defined by the start of Nivo to death by any cause. Progression-free survival (PFS) was
defined by the Nivo start to disease progression or death by any cause. Descriptive statistics were used to evaluate population characteristics. Time-to-event variables were analyzed by Kaplan-Meier curves and the Log-rank test. Cox regression was used for multivariate analysis.

Resultado

Between January 2016 and January 2021, 72 mRCC pts were included. Median follow-up was 36 months(m). Median age at
metastasis was 56 years; most were men(68.1%),Caucasian(86.4%), with clear-cell histology(79.2%) and intermediate risk by the International Metastatic RCC Database Consortium (IMDC) before Nivo(51.5%). 15.9% had a sarcomatoid (Sc) and 36.4% a rhabdoid (Rc) component in the tumor. The objective response rate (ORR) was 29.2%, and it was negatively impacted by the presence of liver metastasis(p=0.002). Clear-cell histology and Sc were associated with better ORR (p=0.02 and p=0.004, respectively). The median OS was 37m (95%CI 31.0-42.9). Bone metastasis was associated with lower overall survival in uni and multivariate analysis (21 vs 40m,HR 0.40 95%CI 0.19-0.85;p=0.02). The median PFS was 10m(95%CI 6.3-13.6) and it was lower in pts with thrombocytosis (3vs10m; HR 0.49 95%CI 0.30-0.80;p=0.004). There was a trend to lower OS for high-risk pts by the IMDC before 2L in multivariate analysis (p=0.08).

Conclusão

Bone metastasis negatively impacted OS in patients with advanced renal cell carcinoma treated with immunotherapy in second line or beyond. Considering the current transfer of ICIs to first-line therapy, this prognostic factor should be further investigated in this scenario since it may suggest an indication of the need of tyrosine kinase inhibitors association with immunotherapy.

Palavras-chave

Renal cell carcinoma; Nivolumab; Bone metastasis