Metastatic RCC patients may benefit from sequential TKI strategy

By medwireNews Reporters

For patients with metastatic renal cell carcinoma (RCC), sequential tyrosine kinase inhibitor (TKI) therapy may be better option than changing to a mammalian target of rapamycin inhibitor (mTORi), research suggests.

Of the 241 patients with metastatic clear cell RCC who had received first-line TKI for at least 6 months before discontinuing owing to disease progression, toxicity or other reasons, 118 went on to receive second-line treatment with a different TKI while 123 switched treatments to an mTORi.

When duration of first-line therapy was used as a continuous covariable, second-line TKI was associated with significantly improved progression free-survival compared with second-line mTORi treatment, at a median of 7.9 and 5.2 months, respectively. The hazard ratio (HR), calculated by averaging various datasets to correct for the effect of missing data outcomes, was 0.75.

Reza Elaidi, from Hôpital Européen Georges Pompidou in Paris, France, and co-workers note, however, that this benefit was mostly attributed to subgroup of participants with an 11- to 22-month duration of first-line therapy. Progression-free survival in this subgroup was 11.2 months for second-line TKI versus 3.9 months with second-line mTORi, giving an average HR of 0.50.

Time to treatment failure was also significantly longer for patients given sequential TKI therapy compared with TKI followed by an mTORi, and this was true for the whole cohort and for patients whose first TKI duration was 11 to 22 months, with mean HRs of 0.75 and 0.65, respectively.

Elaidi et al observe in the Annals of Oncology that “long-term second-line responders were more likely to have received a second TKI than an mTORi and to have been long-term responders to first-line TKI.”

While emphasising the need for clinical trials to confirm their findings, the team concludes: “Our findings suggest that a second-line TKI might be a pragmatic and beneficial option in long-term responders to a first-line TKI (between 11 and 22 months) in whom drug toxicity is manageable.”

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