Favorable Outcome in Elderly Asian Patients with Metastatic Renal Cell Carcinoma Treated with Everolimus: The Osaka Urologic Oncology Group

  • Published : 2014.02.28


Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.


  1. Eisen T, Sternberg CN, Robert C, et al (2012). Targeted therapies for renal cell carcinoma: review of adverse event management strategies. J Natl Cancer Inst, 104, 93-113.
  2. Busch J, Seidel C, Kempkensteffen C, et al (2011). Sequence therapy in patients with metastatic renal cell carcinoma: comparison of common targeted treatment options following failure of receptor tyrosine kinase inhibitors. Eur Urol, 60, 1163-70.
  3. Calvo E, Escudier B, Motzer RJ, et al (2012). Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer, 48, 333-9.
  4. Eisen T, Oudard S, Szczylik C, et al (2008). Sorafenib for older patients with renal cell carcinoma: subset analysis from a randomized trial. J Natl Cancer Inst, 100, 1454-63.
  5. Escudier B (2010). How to interpret phase II data for everolimus plus bevacizumab in renal cell carcinoma. J Clin Oncol, 28, 2125-6.
  6. Escudier B, Albiges L, Blesius A, et al (2010). How to select targeted therapy in renal cell cancer. Ann Oncol, 21, 59-62.
  7. Porta C, Calvo E, Climent MA, et al (2012). Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial. Eur Urol, 61, 826-33.
  8. Reeve BB, Potosky AL, Smith AW, et al (2009). Impact of cancer on health-related quality of life of older Americans. J Natl Cancer Inst, 101, 860-8.
  9. Siegel RL, Ward EM, Jemal A (2012). Trends in colorectal cancer incidence rates in the United States by tumor location and stage, 1992-2008. Cancer Epidemiol Biomarkers Prev, 21, 411-6.
  10. Anandappa G, Hollingdale A, Eisen T (2010). Everolimus a new approach in the treatment of renal cell carcinoma. Cancer Manag Res, 2, 61-70.
  11. Atkins MB, Yasothan U, Kirkpatrick P (2009). Everolimus. Nat Rev Drug Discov, 8, 535-6.
  12. Bellmunt J, Eisen T, Fishman M, et al (2011). Experience with sorafenib and adverse event management. Crit Rev Oncol Hematol, 78, 24-32.
  13. Bellmunt J, Flodgren P, Roigas J, et al (2009a). Optimal management of metastatic renal cell carcinoma: an algorithm for treatment. BJU Int, 104, 10-8.
  14. Bellmunt J, Guix M (2009b). The medical management of metastatic renal cell carcinoma: integrating new guidelines and recommendations. BJU Int, 103, 572-7.
  15. Brenner H, Arndt V (2004). Recent increase in cancer survival according to age: higher survival in all age groups, but widening age gradient. Cancer Causes Control, 15, 903-10.

Cited by

  1. Estimating Radiation Therapy Toxicity and Tolerability with Comprehensive Assessment Parameters in Geriatric Cancer Patients vol.16, pp.5, 2015,
  2. Efficacy and Toxicity of Sunitinib in Metastatic Renal Cell Carcinoma Patients in Egypt vol.16, pp.5, 2015,
  3. A New Tool to Predict Survival after Radiosurgery Alone for Newly Diagnosed Cerebral Metastases vol.16, pp.7, 2015,