Is early change in systemic inflammatory markers associated with treatment response in patients who received pazopanib?

PURPOSE: To demonstrate whether early changes in systemic inflammatory markers are related with pazopanib treatment response in soft tissue sarcoma and renal cell carcinoma. METHODS: Forty-one patients with metastatic clear cell renal carcinoma (mRCC) (n=22) and advanced stage soft tissue sarcoma (STS) (n=19) were assessed. Systemic inflammatory markers such as neutrophils, lymphocytes, c-reactive protein (CRP), mean platelet volume (MPV), lactate dehydrogenase (LDH) and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at both baseline and 1-month of pazopanib treatment were obtained and their relation with the first radiological response about 3-months later after pazopanib treatment was evaluated. RESULTS: Disease control rate (DCR) at the first initial radiological evaluation was 58.5 % for all, it was 77.3% for the RCC group and 36.8% in the STS group. Serum neutrophil, NLR and CRP levels were significantly decreased from baseline in RCC patients who had DCR with pazopanib treatment. Also, serum CRP levels after pazopanib treatment was significantly lower in RCC patients who had DCR (+) rather than those who progressed. CONCLUSIONS: Early decline in serum CRP, neutrophil and NLR levels in RCC patients who received pazopanib at the first month was significantly associated with disease control, assuming a predictive role for the first radiological assessment. However, there was no significant association between change in serum inflammatory marker levels and disease control in STS patients.

Real-life data on first-line Sunitinib and Pazopanib therapy in metastatic renal cell carcinoma patients: a single center experience.

PURPOSE: In this study, we aimed to compare the data of sunitinib and pazopanib used in the first-line treatment of metastatic renal cell carcinoma (RCC) cases and to evaluate the effective factors in terms of survival. METHODS: The records of 125 patients with metastatic RCC admitted between January 2005 and February 2018 were retrospectively analyzed and 63 patients who received pazopanib or sunitinib were included in the study while 62 patients were excluded due to insufficient data. Clinical and histological characteristics, treatment responses, progression-free survival (PFS), and overall survival (OS) of the patients were compared. RESULTS: Patients with metastatic RCC who received pazopanib or sunitinib as tyrosine kinase inhibitors (TKI) in first-line treatment were analyzed; 45 (71.4%) were male while 18 (28.6%) were female, and the median age was 60. 43 (68.3%) patients were treated with sunitinib and 20 (31.7%) with pazopanib. PFS ​​of pazopanib and sunitinib were 10.6 and 7.2 months, respectively. Median OS was 14.5 months in patients receiving pazopanib and 13.6 months in those receiving sunitinib. There was no statistical difference in PFS and OS between both treatments. The median OS of clear-cell RCC was 15.2 months, while of non-clear-cell RCC was 7.7months. CONCLUSIONS: High ECOG score, non-clear-cell histology, presence of liver metastasis in metastatic RCC patients were found to be associated with shorter OS and PFS. Sunitinib and pazopanib produced similar OS and PFS rates in first-line treatment of metastatic RCC.

Efficacy of regorafenib in the second-and third-line setting for patients with advanced hepatocellular carcinoma: A real life data of multicenter study from Turkey.

PURPOSE: After failure of the first-line sorafenib treatment in advanced or metastatic stage hepatocellular carcinoma (HCC), regorafenib is one of the newly-approved targeted agents. We aimed to evaluate the efficacy of regorafenib in patients with advanced HCC treated in the second- or third-line setting. METHODS: In this retrospective and multicenter study, advanced HCC patients not eligible for local therapies, who received a second- or third-line regorafenib therapy after progression on the first-line sorafenib or sequential therapy with chemotherapy (CT) followed by sorafenib, were included. RESULTS: In the first-line setting, 28 (28.9%) patients received CT and 69 (71.1%) patients received sorafenib. There were 24 (24.7%) patients who were intolerant to sorafenib. Disease control rate (DCR) was 53.6% for all patients treated with regorafenib, 62.3% in patients who received regorafenib in the second-line, and 32.1% for those receiving regorafenib in the third-line (p=0.007). Median progression-free survival (PFS) and overall survival (OS) were 5.6 (range; 4.3-6.9) and 8.8 (range, 6.3-11.3) months for all patients treated with regorafenib vs. 7.1 months and 10.3 months for patients who received regorafenib in the second-line vs. 5.1 and 8.7 months for patients who received regorafenib in the third-line, respectively; however, there was no statistically significant difference (pPFS=0.22 and pOS=0.85). CONCLUSION: Although receiving CT as a first-line therapy in advanced HCC patients did not affect the survival rates of subsequent regorafenib therapy, it might diminish the DCR of regorafenib.

Comparison of skeletal muscle mass loss in patients with metastatic colorectal cancer treated with regorafenib or TAS-102.

PURPOSE: To assess whether regorafenib and TAS-102 treatments are associated with a change in Skeletal Muscle Area (SMA) as well as to compare Skeletal Muscle Mass (SMM) loss levels between regorafenib and TAS-102 treatments and prognostic significance in the patients with metastatic colorectal cancer (mCRC). METHODS: A total of 36 mCRC patients, who received regorafenib or TAS-102 in the third-line and subsequent settings were assessed in the analysis. SMM changes were assessed with CT scans findings, and they were categorized into two groups as SMM-loss (SMM decrease ≥2%) and SMM-stable (SMM change <2%). RESULTS: The SMM change after regorafenib therapy was significantly worse compared with TAS-102 therapy (p=0.001). The median overall survival (OS) was longer in SMM-stable group than in SMM-loss group (12.8 months; 95%CI:9.8-15.7) vs. 6.4 months; 95%CI:5.2-7.7, respectively;p=0.04). Cox regression analysis showed that SMM loss was independent prognostic indicator for OS (HR, 2.87; 95%CI: 1.07-7.42, p=0.03). CONCLUSION: Although patients who received regorafenib had more SMM loss than those who received TAS-102, there was no difference in OS between drugs.

Value of MRI apparent diffusion coefficient for assessment of response to sorafenib in hepatocellular carcinoma.

PURPOSE: Efficient and adequate evaluation of therapeutic response in hepatocellular carcinoma (HCC) is an evolving field. We aimed to evaluate apparent diffusion coefficient (ADC) values in the prediction of response to sorafenib and prognosis in patients with advanced HCC. METHODS: Baseline magnetic resonance (MR) imaging was performed before treatment. After sorafenib started, clinical and radiological response were evaluated at approximately 3 months later. ADC measurements were performed by a 12- year experienced radiologist who evaluated MR before and after sorafenib therapy. RESULTS: A total of 17 patients (median age 60 years, range 51-66 and M/F ratio=3.25/1) were analyzed. A significant increase in ADC levels in responders was observed 3 months after sorafenib therapy. Baseline and post-sorafenib ADC values were not significantly associated with mortality (hazard ratio/HR baseline ADC=1.003, p=0.98) and after sorafenib (HR 0.480, p=0.48, respectively). CONCLUSION: Advanced HCC patients with a favorable response to sorafenib had a significant increase in ADC value at the first radiological evaluation. The predictive and prognostic role of ADC for overall survival is still unknown and further research is needed to investigate any possible association.