Effect of temsirolimus versus interferon-α on outcome of patients with advanced renal cell carcinoma of different tumor histologies

Abstract

Purpose Exploratory subgroup analyses from the phase 3 global advanced renal cell carcinoma (ARCC) trial were conducted to assess the influence of tumor histology on outcome of patients treated with temsirolimus (Torisel) or interferon-alpha (IFN). Patients and methods Patients with ARCC including clear cell and other types such as papillary and chromophobe histologies received either IFN (3 million units [MU] subcutaneously three times weekly, escalating to 18 MU) or temsirolimus (25 mg intravenously weekly). Results Approximately 80% of patients had clear cell and 20% of patients had other histologies, the majority of which were papillary. Patients with clear cell and other RCC histologies, treated with temsirolimus, demonstrated comparable median overall and progression-free survival. In contrast, patients with other RCC histologies, treated with IFN, demonstrated shorter median overall and progression-free survival than patients with clear cell RCC. Hazard ratios for death for treatment with temsirolimus versus IFN were less than 1 for patients regardless of tumor histology. For patients treated with temsirolimus, 59% with clear cell and 68% with other RCC histologies experienced tumor reductions. For patients treated with IFN, 35% with clear cell and 14% with other RCC histologies had tumor reductions. However, temsirolimus did not appear to improve the objective response rate compared to IFN. Temsirolimus resulted in a superior clinical benefit rate compared with IFN, regardless of tumor histology. Conclusion Temsirolimus appears to be efficacious in patients with clear cell and non-clear cell histologies and can, therefore, be used for the treatment of all types of RCC.

Management of advanced kidney cancer: Canadian Kidney Cancer Forum (CKCF) consensus update 2017

“…Other options include sunitinib, sorafenib, temsirolimus, and pazopanib ( Table 2). [63][64][65][66][67] Two phase 2 trials randomized patients to everolimus vs. sunitinib as first-line therapy for non-clear-cell pathologies with crossover allowed at progression. The ESPN trial futility analysis resulted in early termination of the trial due to inferior PFS and OS for everolimus.…”

“…[63][64][65]70 In a phase 2 study, the combination of sunitinib and gemcitabine has been shown to be tolerable and the combination may be more efficacious than either therapy alone. 71 …”

Prise en charge du cancer du rein de stade avancé : Mise à jour 2013 des lignes directrices consensuelles du Forum canadien sur le cancer du rein

“…Parmi les autres options, notons le sunitinib, selon les analyses par sous-groupes de l'essai portant sur l'accès élargi et montrant son innocuité et son efficacité; le sorafénib, selon les analyses par sousgroupes de l'essai ARCCS (Advanced Renal Cell Carcinoma Sorafenib) portant sur l'accès élargi et montrant son innocuité et son efficacité, et le temsirolimus, selon l'analyse par sousgroupes des données des études de phase III [27][28][29][30] . Chez les patients atteints d'un hypernéphrome sarcomatoïde avancé ou métastatique ou d'un hypernéphrome mal différencié, les options incluent le sunitinib, en fonction d'études prospectives et sans randomisation du programme d'accès élargi; le sorafénib, selon l'étude ARCCS prospective et sans randomisation portant sur l'accès élargi; la chimiothérapie, en fonction des études de phase II portant sur des agents comme le 5FU, la gemcitabine, la doxorubicine et des associations de ces agents montrant une efficacité; et le temsirolimus, en fonction de l'analyse par sous-groupes de l'essai pivot de phase III auquel ces patients étaient admissibles [27][28][29]31 .…”

Targeted therapy in patients with poor-prognosis renal cell carcinoma

“…Показатели выживаемости по группам представлены в табл. 2 [14][15][16]. Переносимость темсиролимуса в качестве моно-терапии была лучше, чем ИФН-α.…”

“…Терапия темсиролимусом чаще все-го ассоциировалась с возникновением побочных эф-фектов III-IV степеней тяжести, включавших асте-нию, анемию и гипергликемию, которые выявляли у 11 % пациентов. К наиболее часто встречаемым неблагоприятным явлениям всех степеней тяжести относили гипергликемию (26 %), гиперлипидемию (27 %) и гиперхолестеринемию (24 %), зафиксиро-ванные в группах монотерапии темсиролимусом [14][15][16] …”