Predictive Factors for Second-Line Therapy in Metastatic Renal Cell Carcinoma: A Retrospective Analysis

Abstract

Currently, about 50% of patients with metastatic renal cell carcinoma (mRCC) receive a second-line therapy. Therefore, the choice at each subsequent treatment line remains an important issue. In this retrospective study, we sought to identify pretreatment clinical parameters that could predict the likelihood of a patient receiving a second-line therapy. One hundred and sixty-one mRCC patients who received targeted therapy were evaluated. Descriptive statistics, Kaplan–Meier overall survival (OS), Cox regression, and binary logistic regression models were used for data analysis. Second-line therapy was given to 105 patients (65%). Patients with grade 1 tumor received second-line therapy more frequently than those with grade 2/3 tumors (P = 0.03). Only tumor grade was significantly different between patients receiving, or not receiving, second-line treatment. Median OS was significantly superior in patients receiving second-line therapy (32 versus 14 months; P = 0.007; hazard ratio [HR], 1.75; P = 0.008), patients with grade 1 tumors (130 versus 29 months in G2/3 tumors; HR, 3.85; P = 0.009), and in patients without early tumor progression (41 versus 11 months; HR, 5.04; 95% confidence interval [CI], 3.06–8.31; P < 0.001). In binary logistic regression, we identified early progression to be significantly associated with a higher probability of not receiving a second-line therapy (HR, 2.50; 95% CI, 1.01–6.21; P = 0.048). This study hypothesizes that pretreatment grade and early progression are predictive parameters for the selection of patients for second-line therapy.

Biomarkers defining probability of receiving second-line targeted therapy in metastatic renal cell carcinoma

“…In our study, the proportion of patients not receiving second-line therapy was 43% and was similar to those reported previously [ 6 – 10 ]. Patients in the SL and non-SL groups differed in numerous baseline features, including performance status, diagnosis-to-treatment interval, number of metastatic sites, presence of bone, liver and brain metastases, haemoglobin, calcium, albumin and platelet count, which are widely recognised as independent RCC prognostic factors [ 23 ].…”

“…Not surprisingly, it translated into more frequent assignment of patients in the non-SL group to the IMDC intermediate- and poor-risk groups than those in the SL group. Additionally, patients in the SL group had less frequently Fuhrman grade 3–4 histopathology which stays in accordance with previous report stating that patients with grade 1 tumour received second-line therapy more frequently than those with grade 2/3 tumours [ 6 ]. Likewise in other reports, in patients ineligible for second-line treatment—the IMDC status at first-line treatment initiation is more often intermediate (~ 50) or poor (~ 40%), age is higher (age > 75 in ~ 40%), nephrectomy was less often performed (~ 60%), but metastases are more often found in liver (~ 20%), bones (~ 30%), skin/soft-tissue (~ 30%) and central nervous system (13%) [ 12 ].…”

“…Interestingly, PFS and PPS were also shorter in patients not receiving second-line therapy, which may support the thesis that first-line PFS may act as a surrogate end-point for overall OS [ 27 ]. What is more, Eggers et al reported that early progression, defined as progression within 6 months since the start of first-line therapy, was associated with lower probability of having second-line treatment [ 6 ]. However, this parameter will not be known at the start of first-line treatment.…”

“…Moreover, 20% of patients present with initial endogenous resistance to TKIs [ 4 , 5 ]. Out of all patients with mRCC that progress on first-line of treatment, between 20 and 60% will receive second-line therapy [ 6 – 10 ].…”

“…Until now, the Memorial Sloan-Kettering Cancer Center (MSKCC) classification score (Motzer Score) and first-line treatment type were considered as only established predictive factors of receiving second-line therapy [ 10 ]. Moreover, early progression is also significantly associated with a higher probability of not receiving second-line anti-mRCC treatment [ 6 ]. Nevertheless, still little is known on predictive factors of second-line therapy enrolment in RCC patients.…”