A Randomized Phase IIa Trial with Temsirolimus versus Sunitinib in Advanced Non-Clear Cell Renal Cell Carcinoma: An Intergroup Study of the CESAR Central European Society for Anticancer Drug Research-EWIV and the Interdisciplinary Working Group on Renal Cell Cancer (IAGN) of the German Cancer Society

Abstract

Background: Non-clear cell renal cell cancers (nccRCC) are rare entities, and the optimal therapy in metastatic disease has still to be defined. Methods: In this small prospectively randomized phase IIa multicenter trial, we investigated temsirolimus (TEM) versus sunitinib (SUN) as first-line therapy in patients with metastatic nccRCC. The patients were randomized 1: 1 to either TEM in a dose of 25 mg i.v. once a week or SUN with 50 mg p.o. daily for 4 weeks on and 2 weeks off. Primary endpoint was progression-free survival (PFS). In total, 22 patients were included with predominantly papillary RCC (16/22) followed by chromophobe RCC and others. Results: The male to female ratio was 16: 6. The tumor control rate (CR + PR + SD) was 58% for TEM and 90% for SUN-treated patients. There was also a trend for improved PFS with 9.3 versus 13.2 months (HR 1.64; 95% CI 0.65-4.18) in favor of SUN. There was no trend for overall survival. Conclusions: Despite this trial had to be terminated earlier due to low recruitment, the results match the other studies published so far with the mTOR inhibitor everolimus and SUN, which show a trend in favor of SUN for ORR and PFS.

Impact of Value Frameworks on the Magnitude of Clinical Benefit: Evaluating a Decade of Randomized Trials for Systemic Therapy in Solid Malignancies

“…The remaining full-text articles were screened and 108 were excluded, as they were either subgroup analyses, published protocols, treatment for symptoms only, or pooled analyses or reviews. Of the final 438 publications included [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , …”

The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What’s the Story Morning Glory?

“…However, even though the meta-analysis of ESPN and ASPEN pooled data did not display any significant difference in terms of PFS (HR 1.3, p = 0.15), a trend for superiority of sunitinib over everolimus was demonstrated, thus explaining the clinical recommendation preferring sunitinib over mTOR inhibitors [4]. This advantage of sunitinib in terms of survival benefits was recently reached when compared to temsirolimus, in a current phase IIa trial as well [64]. Moreover, the clinical activity of sunitinib in untreated patients with locally advanced or metastatic type 1 and type 2 pRCC was proved in a phase II SUPAP trial, despite being lower than in clear cell histotype (Table 2) [65].…”

Interdisziplinäre Empfehlungen zur Behandlung des fortgeschrittenen Nierenzellkarzinoms

“…[16] In einer weiteren Metaanalyse konnte der Vorteil hinsichtlich des PFS zugunsten von Sunitinib versus Everolimus bestätigt werden [17]. Ähnliche Daten ergaben sich in einer randomisierten Studie mit Sunitinib vs. Temsirolimus [18].…”