Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial

ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma

Axitinib: Oral tyrosine kinase inhibitor for renal cell carcinoma

327 Background: This phase 2 randomized discontinuation trial evaluated tivozanib, a potent and selective vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 kinase inhibitor. Median progression-free survival (PFS) in all pts was 11.8 mo, and the objective response rate (ORR) was 27%. Methods: Pts received 1.5 mg/d tivozanib (3 wk on, 1 wk off = 1 cycle). A retrospective analysis evaluated efficacy and safety by histologic subtype. Response was evaluated by independent radiology review using standard RECIST criteria. Results: 272 pts were enrolled: 70% were male; median age was 56 y (range, 26–79). 226 (83%) pts had clear cell (CC) RCC; 46 had non–clear cell (NCC) RCC, including 11 with papillary RCC. Of pts with CC RCC, 176 (78%) had undergone nephrectomy; of pts with NCC RCC, 23 (50%) had undergone nephrectomy. Median treatment duration was 8.5 mo (range, 0.03– 23.8) as of the data cutoff. Median PFS was 12.5 mo (range, 9.9–17.7) for pts with CC RCC, not yet reached for pts with papillary RCC, and 5.4 mo (range, 3.7–12.0) for pts with other NCC subtypes. ORR and disease control rate (DCR; ORR + stable disease), respectively, were 29% and 85% for pts with CC RCC, 18% and 100% for pts with papillary RCC, and 17% and 74% for pts with other NCC subtypes. For pts with CC RCC, median PFS, ORR, and DCR, respectively, were 14.8 mo, 32%, and 88% for those who had undergone nephrectomy and 8.9 mo, 18%, and 76% for those who had not. Among pts with NCC RCC, median PFS was 6.6 mo for pts who had undergone nephrectomy and 7.2 mo for pts without nephrectomy; ORR was 17% for both NCC subgroups, with a DCR of 78% for pts who had undergone nephrectomy and 83% for pts who had not. Common drug- related adverse events (AEs) for pts with CC and NCC RCC, respectively, included hypertension (49% and 48%), dysphonia (22% and 22%), asthenia (12% and 13%), and diarrhea (13% and 9%). The most common grade ≥3 drug-related AE was hypertension (CC, 8%; NCC, 4%). Conclusions: Disease control was observed for pts with all RCC histologic subtypes. The rate of AEs was similar among patients with CC and NCC RCC and consistent with that of a selective VEGFR inhibitor with minimal off-target toxicities. Tivozanib is currently being tested in a phase 3 trial in pts with CC RCC. [Table: see text]

Background Tumor perfusion may inform therapeutic response and resistance in metastatic renal cell carcinoma (RCC) treated with antiangiogenic therapy. Purpose To determine if arterial spin labeled (ASL) MRI perfusion changes are associated with tumor response and disease progression in metastatic RCC treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Materials and Methods In this prospective study (ClinicalTrials.gov identifier: NCT00749320), metastatic RCC perfusion was measured with ASL MRI before and during sunitinib or pazopanib therapy between October 2008 and March 2014. Objective response rate (ORR) and progression-free survival (PFS) were calculated. Perfusion was compared between responders and nonresponders at baseline, at week 2, after cycle 2 (12 weeks), after cycle 4 (24 weeks), and at disease progression and compared with the ORR by using the Wilcoxon rank sum test and with PFS by using the log-rank test. Results Seventeen participants received sunitinib (mean age, 59 years ± 7.0 [standard deviation]; 11 men); 11 participants received pazopanib (mean age, 63 years ± 6.6; eight men). Responders had higher baseline tumor perfusion than nonresponders (mean, 404 mL/100 g/min ± 213 vs 199 mL/100 g/min ± 136; P = .02). Perfusion decreased from baseline to week 2 (-53 mL/100 g/min ± 31; P < .001), after cycle 2 (-65 mL/100 g/min ± 25; P < .001), and after cycle 4 (-79 mL/100 g/min ± 15; P = .008). Interval reduction in perfusion at those three time points was not associated with ORR (P = .63, .29, and .27, respectively) or PFS (P = .28, .27, and .32). Perfusion increased from cycle 4 to disease progression (51% ± 11; P < .001). Conclusion Arterial spin labeled perfusion MRI may assist in identifying responders to vascular endothelial growth factor receptor tyrosine kinase inhibitors and may help detect early evidence of disease progression in patients with metastatic renal cell carcinoma. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Goh and De Vita in this issue.

Renal cell carcinoma (RCC) is a renal cortical tumor with high clinical incidence. The effect of glutathione peroxidases (GPXs) on RCC and the possible mechanism are still unclear. This study aims to explore the expression level of GPXs gene in RCC and its effect on the clinical prognosis of patients with RCC via bioinformatics analysis. The mRNA expressions of GPXs family genes were obtained from the public data of The Cancer Genome Atlas (TCGA) database. The Kruskal-Wails test was used to analyze the differences in mRNA expression of GPXs family genes between samples from patients with RCC and the normal population. UALAN databases were used to analyze the differences in protein expression of GPXs family genes between samples from patients with renal clear cell carcinoma and the normal population, and to evaluate the role of GPXs family genes in RCC. The Kaplan-Meier Plotter was used to analyze the correlation between different types of RCC and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Kaplan-Meier survival curve was drawn based on the GPX8 gene expression to study the relationship between GPX8 gene expression and prognosis of RCC patients. Based on the results of multivariate Cox regression analysis, a Nomogram scoring model for RCC prediction was established by introducing GPX8 gene. The mRNA expressions of GPX1 and GPX4 were higher in the sample of renal chromophobe cell carcinoma, renal clear cell carcinoma, and renal papillary cell carcinoma than those in the normal population (all P<0.01), and GPX7 and GPX8 were significantly over-expressed in patients with renal papillary cell carcinoma and renal clear cell carcinoma (all P<0.01). Compared with the normal group, the protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in renal clear cell carcinoma (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). The protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in patients with renal clear cell carcinoma at different tumor grades (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). Survival analysis showed that OS, DFS, DSS, and PFS were all decreased in patients with clear cell carcinoma compared with patients with papillary cell carcinoma and chromophobe cell carcinoma. According to the GPX8 level, patients were assigned into the low, medium, and high expression groups. Compared with the low GPX8 level group, the OS (P<0.01), DFS (P=0.03), DSS (P<0.01), and PFS (P=3.18×10-7) were significantly decreased in the high level group. Univariate Cox proportional regression analysis showed that the high level of GPX8 was associated with poor OS of 3 different types of renal cancer. Multifactorial analysis showed that GPX8 was an independent factor affecting the OS of patients with renal papillary cell carcinoma. Race and post tumor node metastasis (pTNM) typing were independent factors influencing the OS of patients with renal clear cell carcinoma. GPX8 and pTMN were independent factors influencing the OS of patients with renal chromophobe cell carcinoma. Based on these variables, the Nomogram risk models of 3 types of cell carcinoma were established, and the discrimination and calibration of the models were evaluated using the Consistency index (C-index) and calibration curves. The C-index of the risk model of renal papillary cell carcinoma was 0.62 (95% CI 0.51 to 1.00, P=0.03). The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) was 0.88. The C-index of the risk model of renal clear cell carcinoma was 0.72 (95% CI 0.52 to 1.00, P=0.03). The results of ROC curve showed that the AUC was 0.90. The C-index of the risk model of chromophobe cell carcinoma of kidney was 0.90 (95% CI 0.85 to 1.00, P<0.01). The results of ROC curve showed that the AUC was 0.59. GPXs family genes, especially GPX8, are potential markers for poor prognosis of RCC, and the occurrence and development of RCC can be predicted in clinical practice based on the expressions of GPXs family genes.

New Horizons in Chemotherapy: Platforms for Combinations in First-Line Advanced Non-small Cell Lung Cancer

Characterization of Patients With Metastatic Renal Cell Carcinoma Experiencing Complete Response to First-line Therapies: Results From the International Metastatic Renal Cell Carcinoma Database Consortium.

The optional regimens of subsequent therapy after failure of anti-programmed cell death protein-1 (PD-1) antibody in metastatic renal cell carcinoma (mRCC) remain to be explored. There are reports of the efficacy of single-agent vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) in patients with mRCC after failure of anti-PD-1 antibody therapy. However, it is not clear whether it is beneficial for patients to receive anti-PD-1 antibody as post-progression treatment. It has great significance to explore whether continuous application of anti-PD-1 antibody is beneficial for patients with mRCC whose diseases progressed to the state of pre-anti-PD-1 therapy. The purposes of this study are to explore the efficacy and safety of subsequent treatment on whether to continue using anti-PD-1 antibody therapy for patients who have progressive mRCC after prior treatment with anti-PD-1 antibody. The clinical data of patients with mRCC from the Department of Immunotherapy in the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital from February 1, 2019 to December 31, 2021 were analyzed retrospectively. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS). The ORR and disease control rate (DCR) were estimated with Fisher's exact test. PFS and overall survival (OS) were assessed using the Kaplan-Meier method and log-rank tests. The associations between potential prognostic variables and PFS were evaluated with univariate and multivariate Cox regression analyses. A P value of less than or equal to 0.05 was deemed as statistically significant. A total of 35 patients were included in this study, during which 19 received VEGFR-TKI monotherapy and 16 received the VEGFR-TKI plus anti-PD-1 antibody therapy. Until the last follow-up on June 30, 2022, 19 patients experienced progressive disease (PD), five were in remission, and 11 kept stable disease (SD). After a median follow-up of 28.7 [95% confidence interval (CI): 17.0-35.6] months, the median PFS (mPFS) was 11.6 months for the VEGFR-TKI group and 9.1 months for the VEGFR-TKI plus anti-PD-1 antibody group [hazard ratio (HR) =0.81, 95% CI: 0.32-1.03, P=0.44]. Median OS (mOS) were 16.9 and 11.2 months respectively (HR =0.99, 95% CI: 0.44-2.27, P=0.90). The ORRs were 26.3% and 0% (P=0.049), and the DCRs were 47.4% and 43.8% (P=0.55) respectively. Treatment-related adverse events (TRAEs) occurred in 14 patients (73.7%) in the VEGFR-TKI group and 14 patients (87.5%) in the VEGFR-TKI plus anti-PD-1 antibody group (P=0.42); grade 3/4 TRAEs occurred in two patients (10.5%) and six patients (37.5%) respectively (P=0.11). VEGFR-TKI monotherapy is an efficacious regimen for patients with mRCC whose diseases progressed on previous anti-PD-1 antibody therapy, and continuous anti-PD-1 therapy after failure of anti-PD-1 antibody could not provide additional clinical benefit but increased the incidence of TRAEs.

Nivolumab alone and in combination with ipilimumab is approved for the treatment of patients with metastatic renal cell carcinoma (RCC) who received prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) and those who are treatment naive, respectively. However, the clinical activity of nivolumab in non-clear cell RCC (nccRCC) is unknown, as these patients were excluded from the trials. We reviewed the records of patients who received nivolumab for nccRCC and ccRCC with >20% rhabdoid with the primary endpoint to assess the objective response rate (ORR). We assessed radiographic response using RECIST, v1.1. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also reviewed the literature to identify studies reporting on the clinical activity of immune checkpoint inhibitors in nccRCC, and performed a meta-analysis of proportions for ORR and disease control rate (DCR). Twelve patients (30%) had papillary histology, 11 (27.5%) had unclassified, 8 (20%) had ccRCC with rhabdoid component, 5 (12.5%) had chromophobe, 3 (7.5%) had translocation, and 1 (2.5%) had mucinous tubular and spindle cell carcinoma. Overall, seven patients (21.6%, 95% confidence interval [CI], 8.7%-37.9%) had an objective response, including three patients (8.8%, 95% confidence interval [CI], 1.9%-23.7%) who achieved a complete remission. At a median follow-up of 24.5 monoths (95% CI, 17.7-32.6), median PFS was 4.9 monoths (95% CI, 3.53-10.27) and median OS was 21.7 monoths (95% CI, 7.83 mo to not reached). There were no treatment-related deaths. We also identified two retrospective studies reporting best ORR in patients with nccRCC receiving PD-1/PD-L1 checkpoint blockade. The ORR and DCR for the total cohort were, respectively, 18.6% (95% CI, 11.9%-26.4%) and 53.4% (95% CI, 44.2%-62.5%). Nivolumab demonstrated activity in unclassified nccRCC and ccRCC with >20% rhabdoid; further randomized clinical trials are warranted. This article reports on the clinical activity and safety of immune checkpoint inhibitors in non-clear cell kidney cancer. The retrospective data with the meta-analysis provides a summary that will help guide the treatment of this rare and heterogeneous group of kidney cancers.

LBA104 Background: We have previously demonstrated that the live bacterial product CBM588 may augment clinical outcomes in pts with mRCC receiving 1st-line (1L) therapy with dual immune checkpoint inhibitors (ICIs; Dizman et al Nature Medicine 2022). As tyrosine kinase inhibitors (TKIs) in combination with ICIs also represent a 1L standard of care in mRCC, we sought to determine if CBM588 would augment clinical outcome with the TKI cabozantinib (cabo) with nivo. Methods: Eligible pts were ≥18 yrs old (Karnofsky performance status ≥70%) with histologically verified (clear-cell, papillary or sarcomatoid component) mRCC and no prior systemic therapy for metastatic disease. Patients were randomized 1:2 to receive either cabo/nivo at the standard dose/schedule (40mg PO QD and 480mg IV monthly, respectively) alone or with CBM588 dosed at 80mg PO BID. The primary endpoint was the relative abundance of Bifidobacterium spp. in stool specimens at baseline and after 12 weeks of treatment. Secondary endpoints included assessment of response rate, overall survival, progression-free survival (PFS), systemic immunomodulation, and toxicity. A two-group t-test with a one-sided type I error of 0.05 was used to assess the study's primary endpoint, hypothesizing an increase in Bifidobacterium spp. with CBM588 therapy. Results: A total of 30 (20:10 M:F) pts were recruited; median age was 65 (36-84) and 5 pts (17%) had sarcomatoid features and 2 pts (7%) had predominant papillary histology. 12 (40%), 12 (40%) and 6 pts (20%) had good, intermediate and poor risk, respectively. Metagenomic sequencing of paired stool specimens showed a significant decrease in diversity from baseline to week 12 in patients receiving cabo/nivo (P=0.02); no significant difference was observed in those treated with cabo/nivo+CBM588. No significant change in Bifidobacterium spp. was observed. RR was 63% in pts receiving cabo/nivo+CBM588 vs 33% in pts receiving cabo/nivo alone. Median PFS was not reached in pts receiving CBM588 vs 5.8 mos in pts receiving cabo/nivo along (P=0.03). Grade 3/4 toxicities were observed in 44% and 42% of patients on control and experimental arms, respectively. Conclusions: In the second prospective trial assessing the addition of CBM588 to ICI-based therapy in mRCC, a consistent result with improved PFS and RR was observed. Further translational efforts are underway to characterize the mechanism through which CBM588 augments clinical activity. Clinical trial information: NCT05122546 .

506 Background: Neurofibromin-2 (NF2) is a tumor suppressor gene that encodes the scaffolding protein merlin and is commonly mutated in rare RCC subtypes: unclassified (uRCC), papillary (pRCC), collecting duct carcinoma (CDCA), and the emerging entity, biphasic hyalinizing psammomatous (BHP-RCC). Merlin loss/deficiency by immunohistochemistry (IHC) was recently demonstrated as a reliable surrogate marker of NF2 genomic alterations (GAs). We report the first clinical outcomes of RCC patients (pts) with merlin-deficiency/biallelic loss of NF2, treated with immune checkpoint inhibitor (ICI) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI) therapies. Methods: In our single institutional cohort, we identified 27 pts with high-grade morphology suggestive of BHP-RCC or unclear subtype. All pts had merlin deficiency (by IHC) and 12/16 pts with genomic data were found to have also had biallelic NF2 loss (by next-generation sequencing). Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were evaluated. Survival curves were generated using the Kaplan-Meier method. Results: In the overall cohort (N=27), histologic subtypes included pts with BHP-RCC (N=19), uRCC (N=6), pRCC (N=1), and CDCA (N=1). The median age at diagnosis was 56 and 74.1% (N=20) had metastatic disease. Seventeen pts received systemic treatment and 76.5% (N=13) were treated with ICI-based regimens (Table). In metastatic cohort, median PFS and OS were 4.9 and 24.5 months, respectively. ORR was 28.6% in metastatic pts treated with systemic treatment, with the rate of 18.2% and 66.7% (p=0.18) in those treated with ICI and non-ICI, respectively. Pts treated with ICI and non-ICI had also similar OS (p=0.44), and PFS (p=0.14). In pts with “classic” BPH-RCC morphology who received systemic treatment (N=10), ORR was 25% and median PFS was 4.9 months, while OS did not reach median. In metastatic other merlin-deficient subtypes who received systemic treatment (N=7), ORR was 33.3%, and median PFS and OS were 6.6 and 24.5 months, respectively. No statistically significant differences in ORR (p=1.00), PFS (p=0.93) or OS (p=0.60) were observed between BHP-RCC and other merlin-deficient subtypes. Conclusions: Merlin protein loss by IHC has emerged as a surrogate for biallelic NF2 GAs, which are associated with rare and aggressive RCC subtypes including BHP-RCC. Despite exposure to standard ICI and VEGFR TKI therapies, few pts with merlin deficient RCC derived clinical benefit and prognosis remains poor. Systemic treatment for metastatic disease (n=17). ICINivolumab+IpilimumabNivolumab+Ipilimumab+CabozantinibNivolumab+CabozantinibPembrolizumab+AxitinibAtezolizumab+BevacizumabAtezolizumabNon-ICICabozantinibEverolimusChemotherapy 13 (76.5) 6 (35.2)3 (17.6)1 (5.8)1 (5.8)1 (5.8)1 (5.8) 4 (23.5) 2 (11.7)1 (5.8)1 (5.8)

ABSTRACTIntroduction: Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy.Areas covered:The preclinical development and scientific rationale, pharmacokinetics, and clinical efficacy and safety of cabozantinib for the treatment of advanced RCC are reviewed. The use of cabozantinib in clinical practice with the growing number of available treatments for advanced RCC is discussed.Expert opinion: Cabozantinib is the only therapy for advanced RCC that has improved PFS, ORR, and OS in a pivotal phase 3 trial after prior antiangiogenic therapy. While no clinical trials have been published comparing cabozantinib with another TKI, available clinical data suggest it could be the most efficacious TKI for second-line therapy. Preliminary encouraging results have also been reported in a phase 2 trial in untreated poor- and intermediate- risk patients with RCC, indicating that treatment with cabozantinib may also be beneficial in the first-line setting.

Purpose Cabozantinib, an inhibitor of tyrosine kinases including MET, vascular endothelial growth factor receptors, and AXL, increased progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in patients with advanced renal cell carcinoma (RCC) after previous vascular endothelial growth factor receptor-targeted therapy in the phase III METEOR trial. Because bone metastases are associated with increased morbidity in patients with RCC, bone-related outcomes were analyzed in METEOR. Patients and Methods Six hundred fifty-eight patients were randomly assigned 1:1 to receive 60 mg cabozantinib or 10 mg everolimus. Prespecified subgroup analyses of PFS, OS, and ORR were conducted in patients grouped by baseline bone metastases status per independent radiology committee (IRC). Additional end points included bone scan response per IRC, skeletal-related events, and changes in bone biomarkers. Results For patients with bone metastases at baseline (cabozantinib [n = 77]; everolimus [n = 65]), median PFS was 7.4 months for cabozantinib versus 2.7 months for everolimus (hazard ratio, 0.33 [95% CI, 0.21 to 0.51]). Median OS was also longer with cabozantinib (20.1 months v 12.1 months; hazard ratio, 0.54 [95% CI, 0.34 to 0.84]), and ORR per IRC was higher (17% v 0%). The rate of skeletal-related events was 23% with cabozantinib and 29% with everolimus, and bone scan response per IRC was 20% versus 10%, respectively. PFS, OS, and ORR were also improved with cabozantinib in patients without bone metastases. Changes in bone biomarkers were greater with cabozantinib than with everolimus. The overall safety profiles of cabozantinib and everolimus in patients with bone metastases were consistent with those observed in patients without bone metastases. Conclusion Cabozantinib treatment was associated with improved PFS, OS, and ORR when compared with everolimus treatment in patients with advanced RCC and bone metastases and represents a good treatment option for these patients.

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

LBA4537 Notice of Retraction: "Axitinib versus sorafenib as second-line therapy in Asian patients with metastatic renal cell carcinoma (mRCC): Results from a registrational study." Abstract LBA4537, published in the 2012 Annual Meeting Proceedings Part II, a supplement to the Journal of Clinical Oncology, has been retracted by Shukui Qin, MD, on behalf of all authors of the abstract. The adjudication portion of the Independent Review Committee (IRC) tumor assessments were incomplete for some of the ongoing patients in the study reported in the abstract and the adjudication could not be completed in time for presentation at the 2012 ASCO Annual Meeting. Background: An earlier phase III trial in 723 patients with previously treated mRCC demonstrated significantly longer progression-free survival (PFS) for axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, compared with sorafenib. We conducted a multicenter, randomized, open-label trial to estimate PFS for axitinib and sorafenib in 204 Asian patients with previously treated mRCC. Methods: Patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 and measurable, clear-cell, mRCC that had progressed after 1 prior first-line systemic regimen (sunitinib or cytokines) were randomly assigned (2:1) to 28-day cycles of axitinib 5 mg twice daily (BID) or sorafenib 400 mg BID. Axitinib dose reductions and stepwise dose titrations to 7 mg BID and then 10 mg BID, as tolerated, were allowed; sorafenib dose reductions to 400 mg daily or every other day were also allowed. Primary endpoint was PFS per independent review committee. Results: Patients were stratified by ECOG PS and prior first-line systemic therapy: 135 received axitinib and 69 received sorafenib.Baseline patient characteristics included median age 56 years, 70% male, 99% Asian, and 63% ECOG PS 0. Prior therapy included sunitinib (45%) or cytokines (53%). Median PFS was 6.4 months (95% confidence interval: 4.6, 8.3) with axitinib and 4.8 months (2.8, 6.5) with sorafenib. Objective response rates were 23.7% with axitinib and 10.1% with sorafenib. All-grade adverse events in ≥15% of patients (axitinib, sorafenib) included hypertension (50%, 36%), weight decreased (37%, 33%), diarrhea (34%, 30%), hand-foot syndrome (32%, 57%), decreased appetite (30%, 20%), hypothyroidism (28%, 23%), fatigue (27%, 23%), proteinuria (21%, 20%), dysphonia (19%, 9%), cough (16%, 16%), rash (15%, 28%), pyrexia (7%, 16%), alopecia (3%, 22%). Conclusions: Asian patients receiving axitinib as second-line therapy for mRCC had a similar PFS and objective response rate as in a previous global phase III trial, with an acceptable safety profile.