Outcomes of Patients With Long-Term Treatment Response to Vascular Endothelial Growth Factor-Targeted Therapy for Metastatic Renal Cell Cancer.

BACKGROUND: Although targeted therapies with inhibitors of the vascular endothelial growth factor (VEGF) are the mainstay of treatment for metastatic renal cell carcinoma, there are limited data on the outcome of patients with long-term response to this treatment. PATIENTS AND METHODS: In a retrospective, registry-based study, patients continuously treated with first-line anti-VEGF agents for at least 24 months were included. In total, 219 patients had evaluable data and were included in the outcome analysis. RESULTS: Median progression-free survival (PFS) after initiation of first-line targeted therapy was 39.7 months (95% confidence interval [CI], 35.9-43.5 months), with 5-year PFS of 34.2% (95% CI, 27.2%-41.2%). Median overall survival (OS) reached 79.1 months (95% CI, 65.2-93.0 months) with the 5-year OS of 62.1% (95% CI, 54.5%-69.7%). In this cohort, 28, 103, and 88 patients achieved complete response (CR), partial response (PR), or stable disease (SD) as the best response, respectively. Median PFS and OS were comparable in patients with PR and SD, but significantly longer in patients with CR (log rank test P value for PFS difference < .001 and .009 for OS difference). CONCLUSION: There are marked differences in PFS and OS between patients who receive long-term anti-VEGF treatment, achieving CR and non-CR as the best clinical response. Patients with non-CR experienced a relatively high progression rate shortly after the landmark time point of 2 years.

Comparing Clinical Characteristics and Outcomes of Young-onset and Late-onset Colorectal Cancer: An International Collaborative Study.

BACKGROUND: Compared with the general population, the incidence of young-onset (YO) colorectal cancer (CRC) is increasing. However, a significant knowledge gap exists in the clinical characteristics, treatment patterns, and outcomes for these patients. MATERIALS AND METHODS: Six international tertiary cancer centers conducted a retrospective study. Patients with YO CRC (aged 18-44 years) and LO CRC (aged > 44 years) diagnosed with histologically proven colorectal adenocarcinoma from June 2003 to June 2014 were enrolled. Patients were randomly chosen from each center's database, and the patient demographics and treatment information were collected. The data were then centralized, and the final analysis was performed at a single institution. Cox proportional hazards models were used to estimate the crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for progression-free survival and mortality, and YO was compared with LO. Site-specific HRs were pooled using a random-effects meta-analysis. RESULTS: Overall, 498 patients, including 224 with YO (129 men; mean age, 37 ± 5.5 years) and 274 with LO (167 men; mean age, 64.8 ± 9.5 years) CRC, were included. At the diagnosis, 137 patients (61.2%) and 122 patients (44.5%) with YO and LO CRC had metastatic disease, respectively. For both cohorts, the 3 most common presenting symptoms were pain, hematochezia, and weight loss. Surgery was performed in 141 YO (63.0%) and 219 LO (79.9%) patients. The longitudinal noncurative treatment patterns were similar, but more biologic therapy was used for these YO patients. The pooled progression-free survival analysis results for first-line noncurative treatment favored LO (HR, 1.96; 95% CI, 1.04-3.68). The mortality analysis showed no significant differences between the 2 groups (YO: HR, 1.53; 95% CI, 0.91-2.58). CONCLUSION: Despite similar treatment patterns and survival outcomes, YO disease might be clinically more aggressive.

Outcomes for Patients with Metastatic Renal Cell Carcinoma Achieving a Complete Response on Targeted Therapy: A Registry-based Analysis.

BACKGROUND: It is currently not known whether treatment with anti-vascular endothelial growth factor agents for metastatic renal cell carcinoma (mRCC) can be safely discontinued in patients achieving a complete response (CR). OBJECTIVE: To assess outcomes for patients with mRCC achieving CR on targeted therapy (TT) and the survival of patients discontinuing TT after CR. DESIGN, SETTING, AND PARTICIPANTS: A national registry was used to identify patients achieving CR during first-line TT using bevacizumab, sunitinib, sorafenib, or pazopanib. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with outcomes were analysed using a log-rank test. RESULTS AND LIMITATIONS: A total of 100 patients achieving CR were identified out of 2803 patients. The median time to CR was 10.1 mo. Median progression-free survival (PFS) from TT initiation was 3.8 yr (95% confidence interval [CI] 2.9-4.6 yr) and the 5-yr overall survival (OS) was 80% (95% CI 70-91%). Patients discontinuing TT within 1 mo after achieving CR and those continuing TT beyond CR had similar OS (CI for difference in 2-yr post-CR OS -13% to 19%; p=0.3) and PFS (CI for difference in 2-yr post-CR PFS -29% to 17%; p=0.7). The limitations include the retrospective, registry-based data analysis. CONCLUSIONS: Achievement of CR on TT for mRCC was associated with excellent long-term prognosis. No significant differences in post-CR survival were observed between patients discontinuing TT after the date of CR and those who continued on TT, although the wide CIs cannot exclude important differences between the groups. PATIENT SUMMARY: According to this registry-based analysis, patients with metastatic renal cancer with no signs of disease (complete response) after treatment with targeted agents experience excellent long-term survival even if the treatment does not continue beyond the date of complete response.

Clinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma treated with sunitinib and sorafenib after progression on cytokines.

OBJECTIVES: The aim of this retrospective study was to analyze prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors (TKIs) sunitinib or sorafenib after progression on cytokine therapy. MATERIALS AND METHODS: A national database of patients treated with targeted agents was used as the data source. A total of 319 patients treated with sunitinib (n = 181) or sorafenib (n = 138) after progression on cytokine therapy were analyzed. RESULTS: Prognostic factors significantly associated with poor overall survival in a multivariable Cox model included the time from diagnosis to the start of treatment with TKIs<1 year, increased neutrophil counts, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. The parameters showing statistically significant association with progression-free survival included time from diagnosis to the beginning of treatment with TKI<1 year, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. We have also validated the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model in our cohort of patients. CONCLUSION: We demonstrate that the International Database Consortium prognostic model performs well for European patients treated with TKIs, including sunitinib or sorafenib, after progression on cytokines and suggest that a reduction from original 6 down to 4 parameters is possible.

Objective response and time to progression on sequential treatment with sunitinib and sorafenib in metastatic renal cell carcinoma.

Patients with metastatic renal cell carcinoma (mRCC) are often treated sequentially with targeted agents, although the optimal strategy is not known. A retrospective, registry-based study has been carried out to assess correlation between clinical response and progression-free survival in patients with mRCC treated sequentially with tyrosine-kinase inhibitors (TKIs) sunitinib and sorafenib. Data on 218 mRCC patients treated with sunitinib and sorafenib who completed therapy with both TKIs were obtained from a database of mRCC patients. Standard nonparametric methods were used to assess correlation between response, PFS and length of treatment on the two agents. A strong correlation between responses to first- versus second TKI was observed (p < 0.001). No significant association was noted between the duration of therapy with the two TKIs (p = 0.056), although there was a weak statistically significant correlation between progression-free survival times in the subgroup patients who discontinued treatment because of disease progression. In conclusion, the duration of response on first TKI is of limited value in selecting mRCC patients for sequential TKI therapy. There is a strong correlation between the types of tumour response on the first- versus the second TKI.