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12-08-2013 | Article

mTOR inhibitor retains efficacy down the line in mRCC


Free abstract

medwireNews: Patients with metastatic renal cell carcinoma (mRCC) still stand to gain from mammalian target of rapamycin (mTOR) inhibitor treatment when re-introduced as a third- or even fourth-line treatment, researchers report.

Around a third of patients responded to rechallenge with an mTOR inhibitor when given after failing to respond to sequential treatment with one or two vascular endothelial growth factor receptor–targeted treatments and an mTOR inhibitor.

“Despite the limited number of patients included in this study, our observations demonstrate that the efficacy of an mTOR inhibitor can be preserved when administered in the third-line or fourth-line setting… and highlight the feasibility of utilizing mTOR rechallenge as an integral part of sequential treatment strategies in mRCC,” the researchers Stéphane Oudard (Hôpital Européen Georges-Pompidou, Paris, France) and colleagues report.

Among the 12 mRCC patients, who were considered to be of intermediate risk, seven received everolimus as a first mTOR inhibitor, followed by mTOR inhibitor rechallenge with temsirolimus. Of these patients, 57% responded to first-line everolimus only, 29% to temsirolimus rechallenge only, and 14% to both mTOR inhibitors.

Among the five patients who received temsirolimus followed by everolimus, 20% responded to temsirolimus only, 20% to everolimus rechallenge only, and 60% to neither.

This gave overall response rates of 50% for everolimus and 33% for temsirolimus, irrespective of treatment sequence, with only 25% of patients responding to neither mTOR inhibitor.

The findings suggest that “patients who respond to everolimus as the first mTOR inhibitor are unlikely to benefit from an mTOR inhibitor rechallenge with temsirolimus, whereas patients who do not respond to everolimus as the first mTOR inhibitor may still respond to a rechallenge with temsirolimus,” the team writes in Oncology.

The median treatment duration was 4.5 months longer for patients who received everolimus before temsirolimus, and this was unrelated to prognostic group.

Oudard and colleagues note that the two drugs have distinct clinical pharmacokinetic/pharmacodynamic profiles, which may explain why some patients respond to one but not the other.

While the findings demonstrate the feasibility of mTOR inhibitor rechallenge, the researchers say larger prospective studies are needed to confirm their results.

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Lucy Piper, Senior medwireNews Reporter