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Kidney Cancer Journal 55 In the single arm phase II NeoSun trial, researchers sought to identify efficacy and safety of neoadjuvant and adjuvant sutinib in treatment naive metastatic RCC patients. 14 patients received neoadjuvant sunitinib at 50mg daily with 10 out of the 14 taking the total planned 12 doses. All 14 underwent total cytoreductive nephrectomy, and 13 received adjuvant sunitinib on a repeating 6 week cycle consisting of 4 week-on and 2 week-off, until disease progression. 58.3% of patients achieved confirmed response while 91.7% achieved clinical benefit. Median overall survival was 33.7 months and median progression free survival was 15.7 months. Among the patients who received partial or complete response, the median response time was 8.7 months. It is important to note that there were no unexpected surgical or sunitinibrelated toxicities experienced showing sunitinib is safe when given in the neoadjuvant and adjuvant setting.11 Shepherd and colleagues provided an interesting look at how dynamic changes in clinical labs might help predict survival outcomes in patients receiving VEGF-targeted therapy for advanced clear cell RCC. Multiple models show that markers of systemic inflammatory response have prognostic value in ccRCC prior to starting treatment, but little is known about how dynamic changes in these markers occurring during therapy might be used to predict outcomes. These investigators conducted a retrospective analysis of data form a phase II study evaluating cediranib vs cediranib and saracatinib in patients with relapsed metastatic clear cell RCC. Specifically, they analyzed how haemoglobin, neutrophil count, platelet count, lactate dehydrogenase levels, and C-reactive protein were recorded at randomization, at 8- weeks into the study and at progression for 138 patients. Changes at each time point were compared. This analysis found that a rise in and C-reactive protein or neutrophil count at 8 weeks was predictive of poor outcome, while a fall in hemoglobin was predictive of poor outcomes and progressive disease. Certainly, additional investigation in this area is warranted.12 METEOR Offers Insights on Cabozantinib, Regardless of Nephrectomy The debate regarding the usefulness of cytoreductive nephrectomy in the era of targeted therapies continues. Tannir, et al sought to provide more data to drive the discussion, by analyzing data from the phase 3 METEOR trial. This widely known trial compared cabozantinib to everolimus in 658 patients with advanced clear cell RCC who had previously received at least one VEGFR TKI. 85% of patients enrolled had a prior nephrectomy (7% partial). Tannir’s analysis showed that baseline characteristics were less favorable for those 15% of subjects who had no prior nephrectomy. The analysis showed that cabozanitinib improved progression-free survival, overall survival, OS, and objective response rate when compared with everolimus regardless of nephrectomy status. The median overall survival was longer in the nephrectomy subgroup for both treatment arms (22.0 in those treated with cabozatinib who had a prior nephrectomy, 17.2 months in the everolimus prior nephrectomy group, 16.3 months in those treated with cabozantinib who had no nephretomy, and 12.5 months in patients treated with everolimus and no prior nephrectomy), but these outcomes may be more related to the differences in baseline characteristics than effects of nephrecotmy status.13 There is limited data about outcomes and predictors of patients with long-term response to targeted therapy, but Tannir and colleagues attempted to fill in some of this gap, but analyzing data from the COMPARZ study. They sought to identify patients from COMPARZ who exhibited a long-term response (10 months of greater) to pazopanib and sunitinib and to determine time to response while describing the clinical characteristics of patients who achieved such response. They found that among the 1,110 patients treated on the study, 14% had long-term responses to pazopanib and 13% had long-term responses to sunitinib. PFS was similar in both groups, however, in those treated with pazopanib, there was noted to be a shorter time to achieve a response (11.9 weeks 95% CI, 11.3–12.1 in the pazaopnib group compared to 17.4 weeks; 95% CI, 12.7–18.0) in the sunitinib group, suggesting that this may be a more appropriate therapy for patients who require a more rapid response. 14 While prospective clinical trial data is still the gold standard but which data in the field is judged, there is a more and more understanding as eligibility criteria for trials continues to tighten that outcomes data for real world populations (especially those not eligible for enrollment in prospective clinical trials) is sorely needed. Steven Yip and colleagues retrospectively reviewed real-world outcomes in metastatic RCC patients treated with immunotherapy using data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). They identified 312 patients and found an ORR of 29% in all patients, which was consistent regardless of the line of therapy. They divided those patients treated with immunotherapy in the second-line setting into favorable, intermediate, and poor risk categories using the IMDC criteria and found that while the duration of treatment rate was not reached for those in the favorable risk category, patients in the intermediate risk category had a risk 8.6 months and those in the poor risk category remained on treatment only 1.9 months. Age did not appear to affect outcomes with the therapies.15 Drilling Down Into Data on Rare Kidney Cancers Uncommon forms of RCC and rare diseases associated with the development of kidney tumors were also discussed at the meeting. Eric Jonasch of MD Anderson Cancer Center, who runs one of the world’s only von Hippel- Lindau clinics that focuses on a multidisciplinary approach to treating the kidney tumors and other manifestations of the disease, presented the results of a phase II study of pazopanib in patients with von Hippel-Lindau disease (VHL). This study—the largest prospective VHL- (continued on outside back cover)


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