Early tumor shrinkage predicts targeted therapy efficacy in RCC

By Lucy Piper, Senior medwireNews Reporter

Early tumor shrinkage in patients with metastatic renal cell carcinoma (mRCC) following vascular endothelial growth factor (VEGF)-targeted therapy may herald good long-term survival, research shows.

“Our results demonstrate that patients with a [tumor shrinkage] of at least 60% benefit most and achieve prolonged OS [overall survival] in comparison with others,” report researchers Christoph Seidel (University Medical Center Eppendorf, Hamburg, Germany) and colleagues.

“However, the cohort of patients with such an immense benefit remains small and applies to only 7% in our study population,” the researchers note in the British Journal of Cancer.

This 7% of patients had a median OS of 77.4 months, compared with 28.2 months for the 100 participants as a whole, for whom tumor changes ranged from reductions in size of up to 100% to a gain in size of up to 19%. This is based on analyses of only those patients who survived beyond 6 months.

“Certainly, the study size limits our conclusions, but it also provides a rational that long-term remissions are achievable in mRCC with VEGF [receptor]-targeted therapies, associated with an improved overall survival,” they comment.

The team notes, however, that the 59 patients whose tumors shrank by only up to 59% still achieved survival benefits, with an OS of 33.5 months for those with shrinkage of 30–59% and 26.9 months for those with shrinkage of up to 29%. This compared with 29.9 months for the 15 patients whose tumors increased in size by up to 20% and 14.3 months for the 19 patients who had at least a 20% increase in the occurrence of new lesions indicating progressive disease.

These findings support the notion that it is the depth of remission that is associated with improved overall survival and not just remission itself, Seidel and team point out.

The potential of any early tumor shrinkage to independently predict prognosis in mRCC was confirmed in multivariate analysis, at a hazard ratio of 1.64 compared with patients whose tumors did not shrink. The presence of osseous lesions was also a significant prognostic factor.

Given that an objective response is not required for patients to benefit from targeted therapy, the researchers consider that “additional increments in treatment efficacy or prognosis will apply to subgroups only.”

They therefore suggest that “[i]t may be worthwhile to aim for maximal [tumor shrinkage] to achieve a prognostic impact instead of providing moderate efficacy to the whole group of patients.”

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