Sequential treatment with sorafenib and sunitinib in metastatic renal cell carcinoma: clinical outcomes from a retrospective clinical study

Abstract

Sorafenib and sunitinib are inhibitors of receptor protein tyrosine kinases (TKIs) and are approved for the treatment of metastatic renal cell carcinoma (mRCC). Although the mTOR inhibitor everolimus is effective for the treatment of patients who have failed TKI therapy, it is important to consider all available treatment options before switching therapy mode of action. Herein, we report outcomes in patients with mRCC switched to sorafenib following disease progression on sunitinib treatment. The medical records of 35 patients treated between November 2006 and November 2009 at two large referral centers in Greece were retrospectively analyzed for time-to-progression (TTP), overall survival (OS), and tolerability of sorafenib after sunitinib. Median TTP and OS on sorafenib were 4.9 and 11.5 months, respectively. Among 33 patients evaluable for tumor response, three had a partial response and 17 achieved disease stabilization (objective response rate 8.5%; total clinical benefit rate 57%). Sorafenib was well tolerated, with mostly grade 1/2 adverse events and no treatment-related deaths. Sorafenib was effective and well tolerated in this group of patients. The TTP with sorafenib following sunitinib was comparable to outcomes reported previously, providing further support that TKIs should be used in sequence before switching to an mTOR inhibitor.

Sorafenib rechallenge in patients with metastatic renal cell carcinoma

“…This indicates that efficacy of third line everolimus after treatment with both sunitinib and sorafenib could also be expected. Because a series of retrospective analyses suggest limited cross‐resistance between consecutive TKIs [9–20], the use of sorafenib instead of everolimus as a second line treatment after the failure of first line sunitinib should not be excluded. Furthermore, because many of the above analyses have consistently shown a longer total PFS for a sorafenib–sunitinib sequence ([15–19], reviewed in [3]), first line sorafenib can be regarded as a suitable option from the viewpoint of maximizing total PFS in patients with metastatic RCC, although the final conclusion of an ongoing prospective trial comparing sunitinib‐sorafenib vs. sorafenib‐sunitinib (SWITCH study, NCT00732914 [31]) is still awaited.…”

“…Another is mammalian target of rapamycin (mTOR) inhibitor, including temsirolimus [7] and everolimus [8]. Among them, several retrospective analyses consistently reported the limited cross‐resistance between two TKIs sorafenib and sunitinib ([9–20], reviewed in [1–3]), broadening the options for the order of the drugs in sequential therapy. Furthermore, going a step further than sequential therapy with different agents of similar mechanisms, Zama et al .…”

Systemische und operative Therapie des metastasierten Nierenzellkarzinoms

“…Wie demgegenüber unter Berücksichtigung retrospektiver Serien unter Einschluss von >700 Patienten offensichtlich wird, entfalten Sorafenib und Sunitinib auch in der Zweitlinie nach Therapieversagen gegenüber einer TKIbasierten Erstlinienbehandlung Wirksamkeit [9,10,11,12,13].…”

Simultaneous Optimization of Drug Combination Dose‐Ratio Sequence with Innovative Design and Active Learning

“…Because of drug–drug interactions and the cell–drug interactions, sequential treatment may be a potential way to promote therapeutic efficacy and diminish adverse reactions . Some clinical data have indicated that sequential treatment could be adopted to improve the overall survival of cancer patients with similar tolerability as single‐line treatment …”