Comparison of efficacy, safety, and quality of life between sorafenib and sunitinib as first-line therapy for Chinese patients with metastatic renal cell carcinoma

Molecular targeted therapy has shown promising results in different clinical trials and clinical practice, and it has been the preferred therapeutic option for patients with metastatic renal cell carcinoma (mRCC) [1–5]. Among new therapeutic agents, tyrosine kinase inhibitors (TKIs) such as sorafenib and sunitinib are used as first-line treatment agents for mRCC in China [6]. Although the efficacy of targeted therapies in terms of tumor growth control at metastatic sites is definite, their adverse events (AEs) are often major limitations. Furthermore, it is estimated that the severity of hand-foot syndrome, hypertension, diarrhea, and alopecia was higher in Japanese patients [7] than in Western patients [8, 9]. Thus, comparison of safety in clinical practice would provide important information for patient counseling and treatment decision-making.

According to the data in the Japanese study [7], it is plausible that the quality of life (QoL) of Japanese patients might have been significantly impaired with the use of TKIs. Moreover, because the Chinese ethnicity closely resembles the Japanese ethnicity, the TKI therapy-associated QoL patterns might share similarities. QoL has been a curative effect index and an important parameter to evaluate treatment efficacy in recent clinical practices. Many QoL assessment tools are available. Among them, the Chinese version of the 36-Item Short Form Health Survey Questionnaire (SF-36) has been validated and is the most commonly used tool in Chinese patients [10]. A Japanese study on QoL of patients receiving different TKIs using SF-36 reported that neither sorafenib nor sunitinib was associated with significant impairments in QoL [11].

Efficacy evaluation is important for targeted therapy. Although phase III trials compared the efficacy between pazopanib and sunitinib [12] and between axitinib and sorafenib [13], no such attempts to compare efficacy, safety, and QoL impairments simultaneously between sorafenib and sunitinib as first-line treatment for patients with mRCC have been made. Only three retrospective studies directly compared the efficacy but not QoL impairments between sorafenib and sunitinib. Choueiri et al. [5] reported that the overall response rate was higher in the sunitinib group (37%) than in the sorafenib group (9%) in two oncology centers in the US. In contrast, no significant differences in overall survival (OS) and progression-free survival (PFS) between sorafenib- and sunitinib-treated patients were observed in an Asian population (both P > 0.05), although sorafenib was concluded to be more favorable than sunitinib because of minimal grade 3 or 4 toxicities [14]. Recently, Sheng et al. [15] reported similar results in terms of OS and PFS of Chinese patients with mRCC (both P > 0.05) [15]. However, these studies were conducted with a small sample size and aimed to compare the efficacy and safety of sorafenib and sunitinib, but not the effect of these drugs on QoL.

In the present study, we retrospectively compared the efficacy, safety, and QoL impairments between sorafenib and sunitinib in Chinese patients with mRCC to further guide clinical treatment.

In the present study, we found that sorafenib has comparable efficacy and lower toxicity than sunitinib as first-line therapy for mRCC. AEs were associated with QoL impairments at the role-physical and bodily pain dimensions.

In the present study, the median PFS were 10 months in the sorafenib group and 11.5 months in the sunitinib group (P = 0.366). Our findings were similar to those from a study conducted in Korea by Park et al. [14]. In our study, the median OS were 24 months in the sorafenib group and 23 months in the sunitinib group (P = 0.552). Our data of OS were shorter than those from the Sheng et al. [15] study, but similar to those from the Park et al. [14] study, and proved that both sorafenib and sunitinib are equally effective as first-line treatment of mRCC in Chinese patients.

In addition to efficacy, toxicities of TKIs are significant factors to be considered while prescribing sorafenib and sunitinib. Randomized clinical trials reported that severe or grade 3–4 toxicities occurred in one-third of the patients treated with sorafenib [7] and two-thirds of the patients treated with sunitinib [21]. Hematologic toxicities are more common with sunitinib than sorafenib in our study. However, the severity of hematologic toxicities could be reduced with discontinuation of sunitinib [21, 22]. Increased risks of bleeding and poor healing are also associated with sunitinib [23], which may severely affect the QoL of patients. In our study, the rates of hematologic toxicities such as leukocytopenia (P < 0.001) and thrombocytopenia (P < 0.001) were significantly higher in the sunitinib group than in the sorafenib group, which were consistent with the results of previous studies [14, 15]. Hypothyroidism was also more common in the sunitinib group (P = 0.001), whereas diarrhea was more common in the sorafenib group (P < 0.001). The rates of TKI-related AEs vary among different ethnicities. Ye et al. [6] indicated that Chinese patients were more likely to experience hand-foot syndrome with sorafenib treatment than Western patients, and the occurrence rate in our center was 67.3%. A study in Japan showed that the most frequent AE was elevated lipase followed by hand-foot syndrome and that 10.7% patients had serious AEs [9]. The TARGET study conducted in a Western population showed that diarrhea, rash, fatigue, and hand-foot syndrome were common AEs and hypertension and cardiac ischemia were serious AEs in patients receiving sorafenib treatment [7]. Toxicities of TKIs are also associated with the patient nutritional status. For example, Antoun et al. [24] reported that a low body mass index could be a predictor for a high rate of AEs in patients with mRCC treated with sorafenib. Thus, diverse patient clinical characteristics may lead to diverse rates of AEs in various studies.

Assessment of the changes in QoL after receiving sorafenib or sunitinib treatment is important. Herrmann et al. [25] reported that pretreatment QoL could be a predictor of overall response and OS. Several studies have reported that QoL was not decreased significantly after sorafenib [26] or sunitinib treatment [27]. Furthermore, a phase II randomized controlled trial reported that patients receiving sorafenib treatment had better QoL assessed using the functional assessment of cancer therapy-kidney symptom index (FKSI) and greater treatment satisfaction assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM) compared with patients receiving interferon-alpha treatment [28]. In our study, we observed no significant differences in mean SF-36 scores at all the 8 dimensions between the sorafenib and sunitinib groups at 3 months after the treatment. In a Japanese population, SF-36 scores before and at 3 months after TKI treatment also showed no significant differences [11]. We further analyzed associations between clinicopathologic characteristics and SF-36 scores. There were no significant associations between SF-36 scores and age, sex, MSKCC grade, IMDC risk, or treatment. However, the grade of AEs (grade 1–2 vs. grade 3–4) was independently associated with QoL at the physical functioning (P = 0.017) and bodily pain dimensions (P = 0.005). This result suggested that timely management of AEs of targeted therapy may eliminate their impact on QoL. Furthermore, a Japanese study observed that the 2-day on/1-day off dosing schedule of sunitinib significantly improved QoL compared with the 4-week on/2-week off dosing schedule [29]. Hence, comparison of the efficacy of TKIs with different dosing schedules is warranted for further validation.

This study has several limitations. First, this was a retrospective study at a single center with limited number of patients, which may cause potential bias of the inferences. The study population was limited to Chinese patients. In addition, to be eligible for the analysis, patients needed to have survived beyond 3 months so as to complete the SF-36 questionnaire at both baseline and 3 months after treatment. Second, a few patients who were intolerant to the drugs had dose titrations, and some switched to second-line targeted therapy, which might have influenced their QoL and survival. Third, the median follow-up was relatively short.

We demonstrated that sorafenib and sunitinib, as first-line treatment agents, had comparable efficacy on mRCC. Grade 3–4 AEs of TKIs may impair QoL at role-physical and body pain dimensions. Apart from this, neither of the agents had a negative impact on the overall QoL. Multi-center studies with long-term follow-up are warranted to further validate the findings of the present study.