Multiple lines of targeted therapy extend life for mRCC patients

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By Sarah Pritchard, medwireNews Reporter

Overall survival of patients with metastatic renal cell carcinoma (mRCC) is extended the more lines of targeted therapy (TT) they receive, shows an evaluation of a large retrospective multicentre database.

The survival benchmarks revealed by the analysis provide comparisons for emerging treatment options and “help shape the design of future trials with realistic expectations of outcomes”, suggest the study authors in the British Journal of Cancer.

Among the 2705 mRCC study participants, whose data was obtained from the International mRCC Database Consortium (IMDC), 57% received first-line TT only, 27% received two lines and 16% received three or more lines of TT. The most common first-line therapies were sunitinib, sorafenib and bevacizumab.

After a median follow-up time of 37.0 months, overall survival was significantly longer for those who received second- and at least third-line TT compared with those who received first-line only, at 21.0 and 39.2 versus 14.9 months, respectively. However, the same trend was not observed for progression-free survival, which was longer among patients who received first-line TT only compared with those who also received second- and third-line TT, at 6.7 months versus 3.4 months and 4.0 months.

Multivariate analysis found that receiving second- or third-line therapy was independently and significantly associated with improved overall survival, with hazard ratios of 0.74 and 0.63, respectively.

The researchers then calculated overall and progression-free survival for six subgroups of the IMDC whose TT regimens matched those of six recent large phase III trials.

Average overall survival lengths ranged between 24.8 months for patients who received at least first-line TT after undergoing nephrectomy (who matched the study inclusion criteria for TIVO-1 [A study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma]) and 12.1 months for all patients who received third-line TT.

However, a better overall survival length – 18.0 months – was seen among the subgroup of third-line TT patients who had been previously exposed to at least one vascular endothelial growth factor inhibitor and one mammalian target of rapamycin inhibitor, note Daniel Heng, from the University of Calgary in Alberta, Canada, and colleagues.

Median progression-free survival was also highest among the IMDC patients whose characteristics matched those of TIVO-1 patients, at 8.2 months compared with lengths as low as 3.9 months for the other subgroups.

“Outcomes from real-life cohorts treated with current standard therapies serve as comparators for future clinical trials, with the expectation that newer therapies will perform better than the standard therapies”, conclude Heng and his team.

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