Prolonged exposure to tyrosine kinase inhibitors or early use of everolimus in metastatic renal cell carcinoma: are the two options alike?

Prolonged exposure to tyrosine kinase inhibitors or early use of everolimus in metastatic renal cell carcinoma: are the two options alike?

Med Oncol. 2013 Jun;30(2):578

Authors: Calvani N, Morelli F, Chiuri V, Gnoni A, Scavelli C, Fedele P, Orlando L, Maiello E, Lorusso V, Cinieri S

Abstract
We retrospectively analyzed metastatic renal cell carcinoma (RCC) patients treated with 3 targeted agents. Patients started the sequence with a tyrosine kinase inhibitor (TKI), sunitinib or sorafenib, and were divided into 2 groups based on the order in which they received the other reciprocal TKI and everolimus (EVE): TKI-TKI-EVE group (n�=�19) and TKI-EVE-TKI group (n�=�14). Median progression-free survival (PFS) with first TKI was 13�months in the TKI-TKI-EVE group and 10�months in the TKI-EVE-TKI group. PFS with the second agent showed a trend in favor of the TKI-TKI-EVE sequence, with a median of 11 versus 6.5�months, whereas median PFS with the third agent was 6�months in both groups. Total PFS also showed a trend in favor of the TKI-TKI-EVE sequence with a median of 31 versus 23�months. Median overall survival (OS) was 38�months in both groups, with more patients receiving subsequent treatment in the TKI-EVE-TKI group. The subgroup of patients no long-term responders (?9�months) to first TKI showed similar outcomes irrespective of the sequence. The subgroup of long-term responders to first TKI (>9�months) who received the other TKI instead of EVE had better outcomes in terms of median PFS with the second agent (13 vs. 5.5�months; p�=�0.0271), median total PFS (39.5 vs. 23.5�months; p�=�0.0415), and median OS (46 vs. 38�months). In conclusion, no apparent advantage was observed with early use of EVE in advanced RCC, even in those patients who did not benefit long from first-line TKI, whereas long-term duration of first-line TKI seems to be predictor of second-line TKI efficacy.

PMID: 23613183 [PubMed - in process]

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