Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma

BACKGROUND.

In a randomized, phase 3 trial, sunitinib demonstrated superior efficacy over interferon‐alfa as first‐line therapy in patients with metastatic clear‐cell renal cell carcinoma (RCC). On the basis of outcome data from that trial, the authors developed a nomogram for predicting the probability of 12‐month progression‐free survival for patients who received sunitinib therapy.

METHODS.

Three‐hundred seventy‐five patients who received sunitinib in the phase 3 trial were the subject of the current analysis. Nomogram pretreatment predictor variables included corrected serum calcium levels, the number of metastatic sites, hemoglobin levels, prior nephrectomy, the presence of lung and liver metastases, thrombocytosis, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, and serum levels of alkaline phosphatase and lactate dehydrogenase. Investigator‐assessed progression‐free survival was the predicted outcome endpoint. Internal validation of the nomogram consisted of quantification of the discrimination with the concordance index and assessment of calibration.

RESULTS.

One‐hundred seventy‐four of 375 patients (46%) who received sunitinib achieved an objective response, and the median progression‐free survival was 10.8 months (95% confidence interval, 10.6‐12.6 months). A nomogram for predicting the probability of 12‐month progression‐free survival for patients who received sunitinib therapy was constructed on the basis of a Cox regression model from 11 parameters that were determined before treatment. The concordance index was 0.633.

CONCLUSIONS.

A nomogram was developed from pretreatment clinical features to predict the probability of achieving 12‐month progression‐free survival with sunitinib therapy for metastatic clear‐cell RCC. The authors concluded that independent validation of the nomogram and additional studies to identify tumor‐specific prognostic factors are warranted. Cancer 2008. © 2008 American Cancer Society.     

Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab

BACKGROUND:

Bevacizumab and sunitinib are standard initial therapy in metastatic renal cell carcinoma (mRCC). Despite common use, the safety and activity of sorafenib in bevacizumab‐ or sunitinib‐refractory mRCC have not been prospectively investigated.

METHODS:

Metastatic RCC patients with Response Evaluation Criteria in Solid Tumors (RECIST)‐defined disease progression (PD) after treatment with either bevacizumab or sunitinib received twice daily 400 mg of sorafenib in a multicenter, prospective phase 2 study. Dose escalation was permitted in the absence of significant toxicity. The primary endpoint was tumor burden reduction rate, defined as the proportion of patients with ≥5% reduction in the sum of RECIST‐defined target lesions without other PD. Secondary endpoints included progression‐free survival (PFS), duration of response, overall survival, and safety. A 2‐stage accrual design was used to test the alternative hypothesis that the tumor burden reduction rate was >20% versus <5%.

RESULTS:

Forty‐eight patients were enrolled. The tumor burden reduction rate was 30% (95% confidence interval [CI], 17%‐45%). One unconfirmed objective partial response was observed. The median PFS was 4.4 months (95% CI, 3.6‐5.9). There was no association of PFS and tumor shrinkage with response to prior therapy. Most treatment‐related adverse events were of mild‐to‐moderate intensity, and included fatigue, hypertension, diarrhea, and palmoplantar erythrodysesthesia (PPE). Patients previously treated with bevacizumab tended to develop more PPE (P = .03) and mucositis (P = .06), whereas sunitinib‐treated patients tended to develop more skin rash (P = .06).

CONCLUSIONS:

Administration of sorafenib is safe and feasible in patients with mRCC refractory to either bevacizumab or sunitinib. Modest clinical activity was observed supporting current practice patterns of sequential vascular endothelial growth factor‐targeted therapy in mRCC. Cancer 2010. © 2010 American Cancer Society.     

Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma

Background:

Prognostic factors for progression-free survival (PFS), overall survival (OS), and long-term OS (⩾30 months) were investigated in sunitinib-treated patients with metastatic renal cell carcinoma (RCC).

Methods:

Data were pooled from 1059 patients in six trials. Baseline variables, including ethnicity, were analysed for prognostic significance by Cox proportional-hazards model.

Results:

Median PFS and OS were 9.7 and 23.4 months, respectively. Multivariate analysis of PFS and OS identified independent predictors, including ethnic origin, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, prior cytokine use, haemoglobin, lactate dehydrogenase, corrected calcium, neutrophils, platelets, and bone metastases (OS only). Characteristics of long-term survivors (n=215, 20%) differed from those of non-long-term survivors; independent predictors of long-term OS included ethnic origin, bone metastases, and corrected calcium. There were no differences in PFS (10.5 vs 7.2 months; P=0.1006) or OS (23.8 vs 21.4 months; P=0.2135) in white vs Asian patients; however, there were significant differences in PFS (10.5 vs 5.7 months; P<0.001) and OS (23.8 vs 17.4 months; P=0.0319) in white vs non-white, non-Asian patients.

Conclusion:

These analyses identified risk factors to survival with sunitinib, including potential ethnic-based differences, and validated risk factors previously reported in advanced RCC.     

Buccodental side effects of sunitinib in patients with metastatic renal cell carcinoma

Background:

Sunitinib is a tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC). Few data evaluated severe buccodental adverse events. The aim of this study was to evaluate sunitinib buccodental toxicity in patients with metastatic RCC and to compare it with that of standard chemotherapy in patients with other solid cancers.

Methods:

Patients with RCC treated with sunitinib and patients with other solid tumours treated with chemotherapy were followed for 3 months. Data on dental appliances, oral hygiene/care practices before and during treatment were collected.

Results:

A total of 116 patients were included (58 RCC treated by sunitinib: group S, and 58 treated by chemotherapy: group C). No differences in dental care habits were noted before treatment. In group S, patients reported significantly more frequent pain (P<0.01), teeth instability (P=0.01), gingival bleeding (P=0.01) and change in teeth colour (P=0.02). In all, 58% of patients in this group had to modify their diet (P<0.01). Frequency of dentist'' visits for teeth removal was increased (25% vs 8%, P=0.01).

Conclusion:

Sunitinib seems to increase buccodental toxicity as compared with chemotherapy. This finding emphasises the need for optimal dental care and standardised dental follow-up in patients treated with sunitinib.     

Sunitinib-induced macrocytosis in patients with metastatic renal cell carcinoma

BACKGROUND.: Sunitinib and sorafenib are small molecules that inhibit the vascular endothelial growth factor and related receptors with substantial clinical activity reported in metastatic renal cell carcinoma (RCC). Cytopenia and macrocytosis have been described in patients treated with these agents. METHODS.: A retrospective review of all patients with metastatic RCC who were treated with sunitinib or sorafenib for at least 3 months at the Cleveland Clinic Taussig Cancer Institute was undertaken. Complete blood count (CBC) data including red blood cell indices were recorded at baseline, after 3 months of therapy, and at the end of treatment. RESULTS.: A total of 61 patients were treated with sunitinib and 37 patients were treated with sorafenib with available CBC data. In patients treated with sunitinib, the median corpuscular volume (MCV) increased significantly at 3 months compared with baseline (median increase of 5.1 femtoliters [fL]; P < .001) and continued to increase throughout treatment. Patients who developed hypothyroidism had a larger MCV increase at 3 months than patients who remained euthyroid (P = .06), although macrocytosis was observed in patients without hypothyroidism. Ten patients discontinued sunitinib therapy, and the MCV decreased in all patients within 2 to 4 months, without further intervention. Bone marrow analysis of 4 patients revealed a hypocellular bone marrow with trilineage hematopoiesis and no evidence of metastasis. There was no evidence of folate or vitamin B12 deficiency. In contrast to sunitinib, there was no change in the MCV for patients treated with sorafenib. CONCLUSIONS.: Macrocytosis was a common occurrence after treatment with sunitinib but not sorafenib in patients with metastatic RCC. Sunitinib-induced macrocytosis is reversible with drug discontinuation. Cancer 2008. (c) 2008 American Cancer Society.     

Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma

BACKGROUND:

On the basis of potential additive or synergistic immunostimulatory antitumor effects, in this phase 1 study, the authors evaluated the combination of sunitinib and tremelimumab (CP‐675206; an antibody against cytotoxic T‐lymphocyte–associated antigen 4 [CTLA4]) in patients with metastatic renal cell carcinoma (mRCC) was evaluated.

METHODS:

Adult patients with mRCC who had received ≤1 previous systemic treatment received tremelimumab (6 mg/kg, 10 mg/kg, or 15 mg/kg) intravenously once every 12 weeks and oral sunitinib (50 mg daily for 4 weeks then 2 weeks off or 37.5 mg daily as a continuous dose). The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives were to assess antitumor activity, safety, and pharmacokinetics.

RESULTS:

Twenty‐eight patients were enrolled. Two of 5 patients who received 50 mg sunitinib plus tremelimumab 6 mg/kg experienced dose‐limiting toxicities (DLTs), and no further enrollment to the combination with sunitinib 50 mg dosing was pursued. Among patients who received continuous sunitinib 37.5 mg daily, 1 of 7 patients who received tremelimumab 10 mg/kg plus sunitinib suffered a sudden death, and 3 of 6 patients who received tremelimumab 15 mg/kg plus sunitinib experienced DLTs. An expansion cohort (n = 7) was enrolled at tremelimumab 10 mg/kg plus sunitinib 37.5 mg daily; 3 of those patients experienced DLTs. Overall, rapid‐onset renal failure was the most common DLT. Nine of 21 patients who were evaluable for response achieved partial responses (43%; 95% confidence interval, 22%‐66%), and 4 of those responses were ongoing at the time of the current report.

CONCLUSIONS:

In this study of tremelimumab plus sunitinib, rapid‐onset acute renal failure was observed unexpectedly, and further investigation of tremelimumab doses >6 mg/kg plus sunitinib 37.5 mg daily is not recommended. Preclinical investigation may be warranted to understand the mechanism of renal toxicity. Cancer 2011. © 2010 American Cancer Society.     

舒尼替尼一线治疗转移性肾细胞癌临床疗效分析

目的:观察舒尼替尼一线治疗转移性肾细胞癌疗效及安全性。 方法:2010年4月-2012年4月我科收治转移性肾细胞癌患者31例,采用舒尼替尼行靶向治疗（50mg,pd,4/2方案）。服药期间进行不良事件管理及随访,每间隔2周期行疗效评价,随访截止至2013年8月,Kaplan-Meier分析总体生存期及无进展生存期。结果:随访8-35个月,平均22.3个月,可评价31例,PR 9例(29.0%),SD 14例(45.2%),PD 8例（25.8%）,疾病控制率为74.2%,客观反应率为29%。中位无进展生存期12个月（95%CI:9.2-14.8个月）,中位总生存期21个月(95%CI:17.9-24.1个月)。不良事件多为Ⅰ/Ⅱ级,Ⅲ/Ⅳ级少见,常见的为腹泻、乏力、高血压及造血系统毒性等。41.9%的患者需调整给药剂量或暂时停药,不良事件经管理后可缓解。结论:舒尼替尼治疗转移性肾细胞癌疗效好,安全性较高,是转移性肾细胞癌较好的治疗选择之一。     

The impact of tumor burden characteristics in patients with metastatic renal cell carcinoma treated with sunitinib

BACKGROUND:

An important goal of noncurative therapy for metastatic renal cell carcinoma (mRCC) is tumor burden (TB) control. However, to the authors' knowledge, the impact of TB characteristics on clinical outcome has not been studied in patients with mRCC who were treated with vascular endothelial growth factor‐targeted therapy.

METHODS:

Patients with clear cell mRCC who were treated with sunitinib between June 2004 and October 2007 were retrospectively identified. Computed tomography scans were re‐reviewed from baseline, at the time of maximal TB shrinkage (TS) while receiving sunitinib, and at the time of progressive disease (PD). Measurements were recorded as per Response Evaluation Criteria In Solid Tumors (RECIST).

RESULTS:

A total of 69 patients were identified. The majority (54%) were classified as being of favorable risk using Cleveland Clinic Foundation Tyrosine Kinase Inhibitor (CCF TKI) risk group criteria. All patients underwent prior nephrectomy and 77% received prior systemic therapy. There were a median of 8 metastatic deposits across all organs (range, 1‐27 deposits). The median TB at the initiation of therapy was 14.0 cm (range, 3.0 cm‐42.2 cm). On multivariable analysis, baseline characteristics of disease confined to above the diaphragm (P = .03) and a total TB <13 cm (P = .09) were found to be independent positive predictors of progression‐free survival. A+ baseline, total number of metastases <10 (P < .001) and TB above the diaphragm <6.5 cm (P = .05) were found to be independent positive predictors of overall survival (OS). Increased TS while receiving sunitinib was found to be significantly associated with OS (P < .001). At the time of PD, tumor location and pattern of disease progression were not found to be associated with survival as measured from the date of PD. However, total TB (P = .003) and total number of metastatic deposits (≤12 vs >12; P < .001) were found to be significant predictors of survival after PD.

CONCLUSIONS:

The results of the current study indicate that TB characteristics are associated with clinical outcome in patients with mRCC who are treated with sunitinib. Cancer 2011. © 2010 American Cancer Society.     

舒尼替尼与索拉非尼交替应用治疗肾癌1例并文献复习

目的:探讨舒尼替尼与索拉非尼交替应用治疗转移性肾癌的疗效。方法:报道舒尼替尼与索拉非尼交替应用治疗转移性肾癌1例并结合文献讨论。结果:该患者一线舒尼替尼治疗疾病进展时间（TTP）为6个月。二线索拉非尼治疗TTP为5个月。二线治疗失败后改变舒尼替尼给药方式（37.5mg 每日1次,连续口服）继续治疗,三线TTP为8个月。结论:患者一线应用舒尼替尼和二线应用索拉非尼的治疗疗效与文献报道相符。二线治疗失败后改变舒尼替尼给药方式继续治疗仍获得较好的疗效。     

Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib

Background:

There are no validated markers that predict response in metastatic renal cell cancer (RCC) patients treated with sunitinib. We aim to study the impact of single-nucleotide polymorphisms (SNPs) that have recently been proposed as predictors of outcome to anti-VEGF-targeted therapy in metastatic RCC in an independent cohort of patients.

Methods:

We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy. Association between SNPs, progression-free survival (PFS) and overall survival (OS) were studied by multivariate Cox regression using relevant clinical factors associated with PFS and OS as covariates.

Results:

In a series of 88 patients, both PFS and OS were associated significantly with SNP rs1128503 in ABCB1 (P=0.027 and P=0.025), rs4073054 in NR1/3 (P=0.025 and P=0.035) and rs307821 in VEGFR3 (P=0.032 and P=0.011). Progression-free survival alone was associated with rs2981582 in FGFR2 (P=0.031) and rs2276707 in NR1/2 (P=0.047), whereas OS alone was associated with rs2307424 in NR1/3 (P=0.048) and rs307826 in VEGFR3 (P=0.013).

Conclusion:

Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC. Prospective validation of these SNPs is now required.     

Blood glucose levels in patients with metastatic renal cell carcinoma treated with sunitinib

Sunitinib, a multitargeted tyrosine-kinase inhibitor, extends survival of patients with metastatic renal cell carcinoma (mRCC) and gastrointestinal stromal tumours. Between October 2005 and March 2007, we retrospectively reviewed blood glucose level variations associated with sunitinib therapy in patients treated for mRCC. Nineteen of the patients had type II diabetes. All 19 patients had a decrease in blood glucose level (mean 1.77 mmol l(-1)) after 4 weeks of treatment. This was followed by re-elevation in the 2-week rest period. After two cycles of sunitinib administration, two patients had stopped blood glucose-lowering drugs whereas five other patients had normalised their blood glucose level. On the basis of pre-clinical data, we hypothesise that several mechanisms could be involved in this process, such as capillary regression of pancreatic islets, IGF-1 modulation through HIF1-alpha or NF-kappaB activation. In addition, a decrease of glucose uptake in the context of concomitant gastrointestinal toxicity cannot be excluded. Glycaemic control should be carefully evaluated in diabetic patients treated with sunitinib, and routine monitoring is warranted.     

Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with renal insufficiency

BackgroundPatients with metastatic renal cell carcinoma (mRCC) with renal insufficiency are generally excluded from clinical trials, despite their increasing numbers. Thus, we evaluated the efficacy and toxicity of sunitinib in such patients.Patients and methodsKorean patients with mRCC with renal insufficiency who had received sunitinib as first-line treatment between January 2008 and May 2012 were included. Patient characteristics, clinical outcomes and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) were determined according to the degree of renal impairment.ResultsThe median age of the 34 patients evaluated was 66 years, 90% had an Eastern Cooperative Oncology Group performance status of 0 or 1 and the median glomerular filtration rate was 46.5 mL min⁻¹·1.73 m⁻² (range, 21.1–59.5). The starting sunitinib dose was 37.5 and 50 mg for 12 and 22 patients, respectively. A 4-weeks-on–2-weeks-off regimen was followed for 31 patients; a 2-weeks-on–2-weeks-off regimen, for one patient; and a daily regimen, for two patients. The best response was partial response in eight patients and stable disease in 12. Median OS and PFS times were 26.3 months (95% confidence interval [CI]: 17.1–35.3) and 12.2 months (95% CI: 10.2–13.2), respectively. Common non-haematologic adverse events (AEs) were stomatitis, rash, general oedema and fatigue. The most common AEs of ⩾grade 3 severity were fatigue, neutropenia and thrombocytopenia.ConclusionsIn patients with mRCC with renal insufficiency, sunitinib was efficacious and did not cause increased toxicity. Thus, clinicians should not hesitate to treat patients with mRCC with renal insufficiency with sunitinib.     

Efficacy and safety of sunitinib alternate day regimen in patients with metastatic renal cell carcinoma in Japan: Comparison with standard 4/2 schedule

1 Aim

Sunitinib is a standard agent for metastatic renal cell carcinoma (mRCC). The standard schedule, 4 weeks‐on followed by 2 weeks‐off (4/2 schedule), often does not maintain an adequate dosage because of the severe adverse events (AEs). We compared the efficacy and safety of an alternative every other day (q.a.d.) dosing with that of the 4/2 schedule in mRCC patients.

2 Methods

Of the 55 Japanese patients, 32 and 23 were administered 4/2 (standard group) and q.a.d. schedules (50 or 37.5 mg, every other day; experimental groups), respectively. The AEs, anticancer effects, and trough plasma concentrations of sunitinib were compared between them.

3 Results

The most common AE in the standard group was thrombocytopenia (43.2%), but it was observed in only two patients in the experimental group (8.7%). Although leukopenia and hand‐foot syndrome were both detected in six patients (18.8%) in the standard group, no patients had these AEs in the experimental group. The incidence of dose interruption in the experimental group (21.7%) was significantly lower than that in the standard group was (59.4%, P = 0.005). Time to progression (TTP) and overall survival (OS) of the experimental group were better than those of the standard group (P < 0.001 and P = 0.002, respectively). Mean plasma levels in the experimental group (64.83 ng/mL) were significantly lower than those in the standard group (135.82 ng/mL, P < 0.001) were.

4 Conclusion

Sunitinib administered q.a.d. was safe and effective for mRCC patients. We speculate that the persistent optimal drug plasma concentrations contributed to these effects.     

Phase 1 trial of everolimus plus sunitinib in patients with metastatic renal cell carcinoma

BACKGROUND:

Simultaneous inhibition of the vascular epithelial growth factor (VEGF) and the mammalian target of rapamycin (mTOR) pathway may improve treatment response in advanced renal cell carcinoma (RCC). Everolimus, an oral mTOR inhibitor, and sunitinib, an oral tyrosine kinase inhibitor targeting VEGF, are standard agents in the management of metastatic RCC.

METHODS:

Sequential cohorts of 3 to 6 patients with advanced RCC received dose‐escalated combinations of sunitinib (37.5 or 50 mg daily, 4 weeks on/2 weeks off) with everolimus (2.5‐5 mg daily or 20‐30 mg weekly). Dose‐limiting toxicities (DLTs) were assessed in the first 6‐week cycle to determine maximum tolerated dose (MTD). Pharmacokinetic profiles were obtained.

RESULTS:

Twenty patients (13 clear cell and 7 nonclear cell RCC) were enrolled in 5 cohorts. Daily everolimus was not tolerated when combined with sunitinib; the first 2 patients on the second cohort suffered DLTs. With weekly everolimus, the MTD was 30 mg everolimus on days 7, 14, 21, and 28, plus 37.5 mg sunitinib on days 1 to 28 of a 42‐day cycle; however, chronic treatment was associated with grade 3 and 4 toxicities. A schedule of 20 mg everolimus weekly/37.5 mg sunitinib was tolerated as chronic therapy. Five patients (25%) had confirmed partial responses, and 3 had nonclear cell RCC. No unexpected accumulation of everolimus, sunitinib, or N‐desethyl sunitinib was observed.

CONCLUSIONS:

The combination of everolimus and sunitinib is associated with significant acute and chronic toxicities and is only tolerated at attenuated doses. Responses were observed in nonclear cell and clear cell RCC. Cancer 2012. © 2011 American Cancer Society.     

索拉非尼治疗转移性肾癌的疗效与安全性观察

目的:评估63例转移性肾细胞癌（metastatic renal cell carcinoma,mRCC）患者服用索拉非尼的疗效及安全性。方法:前瞻性观察2010年6月至2018年6月就诊于西安交通大学第一附属医院肿瘤内科及中华慈善总会索拉非尼援助赠药项目mRCC患者共计71例,其中63例可评价疗效及安全性。使用SPSS 18.0 软件进行K-M单因素生存分析,所得阳性因素导入COX回归模型进行多因素分析,明确影响索拉非尼治疗mRCC疗效的因素。结果:63例可评价mRCC患者中,无CR患者,PR 18例,SD 22例,PD 23例,ORR为28.57%（18/63）,DCR为63.49%（40/63）;中位PFS为14月（3~51月）,中位OS为29月（6~69月）;所有不良反应均可控或随剂量减少而降低。索拉非尼作为mRCC一线治疗者39例,二线及以上治疗者24例。一线和二线及以上治疗的ORR及DCR均无统计学差异,且中位PFS分别为24月（4~51月）和13月（3~42月）（P=0.021）。COX回归分析示,索拉菲尼是否为一线治疗是影响PFS的独立危险因素（P=0.030）。结论:索拉非尼治疗mRCC疗效确切,不良反应较少,并且是否为一线治疗是影响患者中位PFS的独立预测因素。     

Baseline quality of life as a prognostic survival tool in patients receiving sunitinib for metastatic renal cell carcinoma

Background:

In a randomized phase III trial of sunitinib vs interferon-alfa (IFN-α) in metastatic renal cell carcinoma (mRCC), better baseline quality of life (QoL) was predictive of longer survival. Using this dataset, we have developed a novel prognostic tool that establishes a relationship between baseline QoL scores and median survival time.

Methods:

Baseline QoL was assessed using the FACT-Kidney Symptom Index-15 item (FKSI-15), its disease-related symptoms (FKSI-DRS) subscale, and the Functional Assessment of Cancer Therapy–General (FACT-G) scale. Weibull models estimated median progression-free survival (mPFS) and overall survival (mOS) as a function of baseline QoL.

Results:

Longer PFS and OS were associated with higher baseline FKSI-15, FKSI-DRS, and FACT-G scores (P<0.05), and baseline FKSI-15 score was the best predictor of survival. For example, for a baseline FKSI-15 score of 60, the predicted mPFS was 67.9 weeks, and predicted mOS was 240.6 weeks. The magnitude of benefit was greater with sunitinib vs IFN-α for a given baseline QoL score.

Conclusion:

This novel tool indicates that baseline FKSI-15 scores were linked to mPFS and mOS in a clear and interpretable way. The results support evaluation of patient-reported QoL symptoms at baseline as a prognostic indicator of survival in clinical research and practice.     

Sunitinib rechallenge in metastatic renal cell carcinoma patients

BACKGROUND:

Sunitinib was a standard initial therapy in metastatic renal cell carcinoma (mRCC). Given the fact that many patients progressed through many available therapies and antitumor activity had been demonstrated with sequential vascular endothelial growth factor‐targeting approaches, a retrospective review was performed of the experience of rechallenge with sunitinib in sunitinib‐refractory mRCC.

METHODS:

mRCC patients who received sunitinib therapy after disease progression on prior sunitinib and other therapy were retrospectively identified. Patient characteristics, toxicity, clinical outcome, Response Evaluation Criteria in Solid Tumors (RECIST) objective response rate, and progression‐free survival (PFS) were recorded.

RESULTS:

Twenty‐three mRCC patients who were rechallenged with sunitinib were identified. Upon rechallenge, 5 patients (22%) achieved an objective partial response. The median PFS with initial treatment was 13.7 months and 7.2 months with rechallenge. Patients with >6‐month interval between sunitinib treatments had a longer PFS with rechallenge than patients who started the rechallenge within 6 months (median PFS, 16.5 vs 6.0 months; P = .03). There was no significant difference in outcome to sunitinib rechallenge based on number or mechanism of intervening treatments. Substantial new toxicity or significantly increased severity of prior toxicity was not seen during rechallenge in this cohort.

CONCLUSIONS:

Sunitinib rechallenge had potential benefits and was tolerated in select metastatic RCC patients. Additional prospective investigation was warranted. Cancer 2010. © 2010 American Cancer Society.