First-line TKI adverse event profile has no bearing on second-line RCC treatment choice

Sep 17 2015

By Shreeya Nanda, Senior medwireNews Reporter

In metastatic renal cell carcinoma (RCC) patients, there is no significant correlation between adverse event profiles of first- and second-line tyrosine kinase inhibitors (TKIs), suggests a Japanese study.

Thus, the second-line targeted treatment can be selected regardless of the adverse event profile during first-line TKI therapy in this patient population, says the team from Kobe University Graduate School of Medicine.

Of 154 patients with metastatic RCC treated between 2008 and 2014, the majority (63.6%) received sunitinib as the first-line TKI while the remaining 36.4% were treated with sorafenib. And sorafenib, axitinib and sunitinib were the second-line agents of choice in 57.1%, 33.8% and 9.1% of patients, respectively.

Focussing on five toxicities – diarrhoea, fatigue, hand–foot syndrome, hypertension and hypothyroidism – the researchers classified patients into three subgroups on the basis of their first-line adverse event profile: those who had no adverse events, those who experienced adverse events of grade 2 or less and those who had adverse events of grade 3 or worse.

The second-line adverse event profile was independent of that during first-line treatment, with no significant between-subgroup differences with respect to the proportion of patients experiencing an adverse event of any grade or of grade 3 or higher for any of the included toxicities.

Of note, a “very low” proportion of patients experienced identical side effects of grade 3 or above during first- and second-line therapy, report the researchers. For instance, grade 3 or worse diarrhoea and hypothyroidism occurred in 11 and 12 patients, respectively, during first-line therapy and in two (18.2%) and one (8.3%) participants, respectively, with the second-line TKI.

Moreover, progression-free and overall survival times were comparable between the 105 participants who did not experience any of the five toxicities during first-line treatment and the 49 who had a grade 3 or worse incidence of at least one of the toxicities.

“This finding indicates that the administration of TKIs as second-line agents to patients who experienced severe [adverse events] during first-line TKI therapy may not have an unfavorable effect on the subsequent prognosis in such patients”, researcher Hideaki Miyake and colleagues observe in Clinical Genitourinary Cancer.

But they caution that their results may not be generalisable as their study comprised just Japanese patients who are known to exhibit adverse event profiles that are different from those seen in western populations.

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