Utilization of Sunitinib for Renal Cell Cancer: an Egyptian University hospital experience: Beyond the Abstract

Since the publication of Motzers’ pivotal trial in 2006 sunitinib was established as one of the standard first line therapies in mRCC ⁽¹⁾. The specific mechanism of its activity in RCC remains unidentified, and thus far not yet feasible to identify specific cohorts of patients who benefit from therapy. Sunitinib and the other drugs are only effective in controlling the disease for a certain period before the eventual progression occurs stressing on the importance of investigating mechanisms of resistance. ⁽²⁾

Cumulative data mainly from Western and Asian countries have reported on their use of sunitinib; hence reporting our institution’s experience as a representative of the African continent in terms of efficacy and adverse events in this different ethnic group may elucidate further to usage of such targeted therapy with this disease.

 

The novelty of reporting in this category of Egyptian patients (49 available for analysis) serves as a further confirmation, primarily, of the unique toxicity profile experienced by this ethnic subset. Considerably higher thyroid adverse events were experienced at our hospital (grades 3
& 4; 10.2%) that can possibly be attributed to previous comorbid related thyroid issues highlighting an area of needed further research. 

Secondly, an alternative schedule was given to a notable portion of the patients (38.8 % received 2 week regimen) in the current study as the first report of its implementation in the region and perhaps accounting for the slight differences in adverse events and lower discontinuation
rate. 

Thirdly, the slightly lower PFS and OS, probably a consequence of the shorter follow up and the higher percentage of patients with cerebral metastases (16.3%); a well-known factor per se for a worse outcome than patients with other sites of metastases. (Gore et al., 2011) 

 
Furthermore, an intriguing point of interest arose when patients were attempted to be stratified according to Heng classification that deemed not possible due to the absence or negligible patients with neutrophilia and thrombocytosis thus making application of MSKCC criteria the only plausible option. This could be attributed to the small sample size primarily but needs to be further validated in a larger study in this community to truly be investigated to draw such a bold conclusion. 

 
Outcomes of the present study are similar to the majority of previous literature, with a slightly lower OS. This lower survival can be explained by the higher percentage of intermediate and poor risk category patients included (71.4%) as well as low performance patient inclusion (ECOG 2= 22.45%) or possibly the short follow-up. An additional factor that explains this diminished PFS and OS is lack of multiple usage of various treatment lines by our patients as a consequence to limited resources (85.7% used sunitinib only) making our survival figures similar to the first sunitinib trials. 

Resemblance to this finding was also stated in the first UK-specific registry to provide information on real-world treatment patterns and outcomes of RCC patients- the RECCORD registry ⁽³⁾. Only 15.8% of the 514 RECCORD patients received second-line therapy, over half treated with everolimus and this clearly influenced median OS (33 months for patients who received second-line treatment vs. those who only received
first-line treatment 20.9 months, P = 0.008). 

Additionally, a study of clinical outcomes in community-based practices published a median overall survival (OS) of 15.5 months, and progression-free survival (PFS) of 7.5 months. They concluded this inferior outcome, as compared to those from clinical trials, a consequence of shorter duration of therapy stressing the importance of sunitinib therapy optimization in this setting.⁽⁴⁾ 

The present study provides a different platform to view RCC disease in a different ethnic group in terms of efficacy and toxicity. The “global community” real life clinical practice echoes somewhat similarly in terms of first and second line therapies employed despite limited access to treatment. Hypothyroidism, as an adverse event, and its association with incidental thyroid abnormalities warrants further investigation in a larger trial to prove if it is of any meaningful association or perhaps linked to disease pathogenesis. Clearly the small limited single institutional sample would be improved if a collaborative database be set not only on a national but an international level. Lack of biomarker use as a prognostic and predictive tool is also another limitation. 

To conclude this study has served to show sunitinib is tolerable and effective in advanced/ metastatic RCC Egyptian patients and implores us to further seek second and third lines to increase survival equivalence as reported by worldwide literature.

1. Motzer RJ, Hutson TE, Tomczak P, et al (2009). Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol, 27, 3584-90.

2. Motzer RJ, Bukowski RM (2006). Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol, 24, 5601-08.

3. Wagstaff J, Jones R, Hawkins R, et al (2016). Treatment patterns and clinical outcomes in patients with renal cell carcinoma in the UK: insights from the RECCORD registry. Ann Oncol, 27, 159-65.

4. Schnadig IA, Hutson TE, Chung H, et al (2014). Dosing patterns, toxicity, and outcomes in patients treated with first-line sunitinib for advanced renal cell carcinoma in community-based practices. Clinical Genitourinary Cancer, 12, 413-21.