A five-factor biomarker profile obtained week 4–12 of treatment for improved prognostication in metastatic renal cell carcinoma: Results from DARENCA study 2

Abstract

Background: Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma (mRCC). The prognostic significance of biomarkers in the early treatment phase is unclear. Material and methods: In a complete national cohort of mRCC patients receiving first-line tyrosine kinase inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 to 2010, overall survival (OS) was analysed for baseline International mRCC Database Consortium (IMDC) classification factors and on-treatment time-dependent biomarkers obtained day 1 each cycle week 4–12 after treatment initiation with multivariate analysis and bootstrap validation. Results: A total of 735 patients received first-line TKI (59%) or IT (41%). Median OS was overall 14.0 months and 33.4, 18.5, and 5.8 months for baseline IMDC favourable, intermediate, and poor risk groups, respectively (p < 0.0001). Systolic blood pressure ≥140 mmHg, neutrophils < lower level of normal (LLN), platelets < LLN, sodium ≥ LLN, and LDH ≤1.5 times upper level of normal after treatment initiation were significantly associated with favourable OS independent of baseline IMDC risk group in multivariate analyses stratified for TKI and IT (p ≤ 0.04). Concordance (C)-index for IMDC classification alone was 0.625 (95% CI 0.59–0.66) and combined with the five-factor biomarker profile 0.683 (95% CI 0.64–0.72). For patients with good (3–5 factors) and poor (0–2 factors) biomarker profile median OS were 23.5 and 9.6 months, respectively (p < 0.0001). Adding the five-factor biomarker profile significantly improved prognostication in IMDC intermediate (25.7 vs. 12.0 months, p < 0.0001) and poor (12.8 vs. 6.4 months, p < 0.0001) risk groups. A trend was seen in IMDC favourable risk group (38.9 vs. 28.7 months, p = 0.112). Conclusion: On-treatment hypertension, neutropenia, thrombocytopenia, LDH below 1.5 times upper level of normal, and normal sodium, obtained week 4–12 of treatment, are independent biomarkers of favourable outcome in mRCC, independent of treatment type.

Hypertension Caused by Lenvatinib and Everolimus in the Treatment of Metastatic Renal Cell Carcinoma

“…The occurrence of sunitinib-induced hypertension has been shown to be associated with improved PFS and/or OS for patients with mRCC and has been proposed as an efficacy biomarker Rini et al reported objective response rates of 54.8% vs. 8.7%, median PFS of 12.5 (95% CI: 10.9–13.7) vs. 2.5 (95% CI: 2.3–3.8) months and OS of 30.9 (95% CI: 27.9–33.7) vs. 7.2 (95% CI: 5.6–10.7) months for patients developing sunitinib-related hypertension vs. patients without hypertension [ 46 ]. Similar effects were observed by additional studies, which also found that the co-occurrence of more than one AE (for example hand-foot-syndrome, neutropenia or thrombocytopenia) is an even stronger predictor of prolonged survival than hypertension alone [ 47 , 48 , 49 , 50 ].…”

Neutrophil-lymphocyte ratio as a predictive biomarker for response to high dose interleukin-2 in patients with renal cell carcinoma

“…Additionally, high preoperative NLR was associated with larger tumor size, higher nuclear grade, histologic tumor necrosis, and sarcomatoid differentiation [8]. Recently, on treatment neutropenia was shown to be an independent biomarker of favorable outcome in mRCC, independent of treatment type [11]. NLR was also recently shown to predict response to ipilimimab in melanoma patients.…”

Folic Acid Reduces Mucositis in Metastatic Renal Cell Carcinoma Patients: A Retrospective Study

“…Some "toxicity" reflects on-target effect and is correlated with favorable outcome and should therefore not be avoided but should be acknowledged and appropriately treated. This is the case with hypertension, neutropenia, thrombocytopenia, hand-foot syndrome, [24][25][26][27] hypothyroidism, 28 and pneumonitis. 29 However, the most common adverse events to TKI associated with daily poor quality of life are fatigue, loss of appetite, diarrhea, nausea, and mucositis.…”