Vol 17, No 3 2019
analyzed. Significant univariate predictors of OS were tested in a multivariate model. There were 100 nccRCC patients treated with CN. Median age was 61 years and 65% were male. There were 79 patient deaths with a median OS of 13.7 months (10.8- 27.2). Estimated 2- and
5-year survival was 40.1% and 12.2%, respectively. Median follow-up of survivors was 13 months. On multivariate analysis, increasing NLR (hazard ratio [HR] 1.27; 95% confidence interval [CI] 1.14-1.40, P < 0.001) and sarcomatoid features (HR 2.18; 95% CI 1.19-3.97, P = 0.014) conferred worse OS and the presence of papillary features were a favorable prognostic feature (HR 0.37; 95% CI 0.21-0.65, P < 0.001).
Conclusion: OS outcomes in patients with nccRCC who underwent a CN were consistently modest throughout the study period. Patients with papillary features and a lower preoperative NLR may be better candidates for a CN.
The impact of corticosteroid use during anti-PD1 treatment. Pan EY, Merl MY, Lin K et al. J Oncol Pharm Pract. 2019 Sep 7:107815521 9872786. doi: 10.1177/ 1078155219872786. [Epub ahead of print]
Summary: Anti-PD1 therapy has the potential to cause immune-related adverse events (irAEs), which can be treated with corticosteroids if severe. The clinical implications of concomitant immunotherapy and systemic steroids remain unclear, as short courses of steroids do not significantly suppress T-cell function. The primary objective of this study is to determine if the use of concomitant steroids impacts the efficacy of anti-PD1 therapy. This retrospective, single-center study reviewed adult patients who received at least four cycles of nivolumab or pembrolizumab for the treatment of melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma from November 2014 to February 2016. Patients who received steroids (prednisone equivalent >10 mg) during anti-PD1 therapy were divided into two main cohorts based on the duration of steroid administration of ≤2 weeks or >2 weeks. Time to disease progression, overall response, and overall survival were assessed. Twenty-seven of 55 patients (13 melanoma, 11 NSCLC, 3 renal cell carcinoma) required steroids during anti-PD1 therapy. In patients who received steroids, median time to disease progression was 5.6 months for melanoma, 5.8 for NSCLC, and 2.0 for renal cell carcinoma. The overall response rate (ORR) was 3/13 (23%) for melanoma, 6/11 (54%) for NSCLC, and 1/3 (33%) for renal cell carcinoma. Median overall survival was 11.9 months for melanoma, 9.9 for NSCLC, and not reached for renal cell carcinoma. Thirteen patients who had received steroids expired; 11 of these patients had received prednisone >10 mg/day for >2 weeks.
Conclusion: High-dose steroids for long durations during anti-PD1 therapy may be associated with poorer survival outcomes.
Angiogenic Factor and Cytokine Analysis among Patients Treated with Adjuvant VEGFR TKIs in Resected Renal Cell Carcinoma. Xu W, Puligandla M, Manola , et al. Clin Cancer Res. 2019 Aug 30. doi: 10.1158/ 1078-0432. CCR- 19-0818. [Epub ahead of print]
Summary: The use of VEGFR TKIs for the adjuvant treatment of renal cell carcinoma (RCC) remains controversial. This study investigated the effects of adjuvant VEGFR TKIs on circulating cytokines in the ECOG-ACRIN 2805 (ASSURE) trial. Patients with resected high-risk RCC were randomized to sunitinib, sorafenib, or placebo. Plasma from 413 patients was analyzed from post-nephrectomy baseline, 4 weeks, and 6 weeks after treatment initiation. Mixed effects and Cox proportional hazards models were used to test for changes in circulating cytokines and associations between disease-free survival (DFS) and cytokine levels. VEGF and PlGF increased after 4 weeks on sunitinib or sorafenib (P < 0.0001 for both) and returned to baseline at 6 weeks on sunitinib (corresponding to the break in the sunitinib schedule) but not sorafenib (which was administered continuously). sFLT-1 decreased after 4 weeks on sunitinib and 6 weeks on sorafenib (P < 0.0001). sVEGFR-2 decreased after both 4 and 6 weeks of treatment on sunitinib or sorafenib (P < 0.0001). Patients receiving placebo had no significant changes in cytokine levels. CXCL10 was elevated at 4 and 6 weeks on sunitinib and sorafenib but not on placebo. Higher baseline CXCL10 was associated with worse DFS (HR 1.41 per log increase in CXCL10, Bonferroni- adjusted P = 0.003). This remained significant after adjustment for T-stage, Fuhrman grade, and ECOG performance status.
Conclusion: Among patients treated with adjuvant VEGFR TKIs for RCC, drug-host interactions mediate changes in circulating cytokines. Elevated baseline CXCL10 was associated with worse DFS. Studies to understand functional consequences of these changes are under way.
First-line Immuno-Oncology Combination Therapies in Metastatic Renal-cell Carcinoma: Results from the International Metastatic Renal-cell Carcinoma Database Consortium. Dudani S, Graham J, Wells C, et al. Eur Urol. 2019 Aug 22. pii: S0302-2838(19)30609-8. doi: 10.1016/j.eururo. 2019.07.048. [Epub ahead of print]
Summary: In metastatic renal-cell carcinoma (mRCC), recent data have shown efficacy of first-line ipilimumab and nivolumab (ipi-nivo) as well as immuno-oncology (IO)/vascular endothelial growth factor (VEGF) inhibitor combinations. Comparative data between these strategies are limited.This study compared the efficacy of ipi-nivo versus IO-VEGF (IOVE) combinations in mRCC, and described practice patterns and effectiveness of second-line therapies. Using the International Metastatic Renal-cell Carcinoma Database Consortium (IMDC) dataset, patients treated with any first-line IOVE combination were compared with those treated with ipi-nivo. All patients received first-line IO combination therapy A First- and second-line response rates, time to treatment failure (TTF), time to next treatment (TNT), and overall survival (OS) were analysed. Hazard ratios were adjusted for IMDC risk factors. In total, 113 patients received IOVE combinations and 75 received ipi-nivo. For IOVE combinations versus ipi-nivo, first-line response rates were 33% versus 40% (P = 0.4), TTF was 14.3 versus 10.2 mo (P = 0.2), TNT was 19.7 versus 17.9 mo (P = 0.4), and median OS was immature but not statistically different (P = 0.17). Adjusted hazard ratios for TTF, TNT, and OS were 0.71 (P = 0.14), 0.65 (P = 0.11), and 1.74 (P = 0.14), respectively. Sixty-four (34%) patients received second-line treatment. In patients receiving subsequent VEGF-based therapy, second-line response rates were lower in the IOVE cohort than in the ipi-nivo cohort (15% vs 45% (P = 0.04; n = 40), though second-line TTF was not significantly different (3.7 vs 5.4 mo; P = 0.4; n = 55). Limitations include the study’s retrospective design and sample size.
Conclusion: There were no significant differences in first-line outcomes between IOVE combinations and ipi-nivo. Most patients received VEGF-based therapy in the second line. In this group, second-line response rate was greater in patients who received ipi-nivo
Copyright © 2019