TWiST Results Favour Pazopanib For Metastatic RCC

Pazopanib may offer metastatic renal cell carcinoma patients more time without treatment toxicity or disease symptoms than sunitinib therapy

medwireNews: Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) analysis favours pazopanib over sunitinib for patients with locally advanced and/or metastatic renal cell carcinoma (mRCC), the COMPARZ investigators report.

“These findings underscore the competing benefits and risks of pazopanib versus sunitinib and may help to guide treatment decision making for patients with mRCC and their providers”, the researchers comment in Cancer.

The phase III trial previously showed comparable progression-free survival (PFS) for the two oral angiogenesis inhibitors but indicated that pazopanib may have better safety and quality of life (QoL) profiles, the researchers explain.

To investigate further, the team partitioned the overall survival of the 557 patients randomly assigned to receive pazopanib and the 553 patients given sunitinib into three blocks of time. These were: time spent with a grade 3 or 4 toxicity (TOX); time spent with no symptoms of disease or grade 3 or 4 toxicity (TWiST); and the time spent after tumour progression or relapse (REL).

This revealed that patients given pazopanib had a median of 31 days fewer in TOX than those in the pazopanib group, report Jennifer Beaumont, from Northwestern University in Chicago, Illinois, USA, and co-workers.

Threshold analysis found that the difference between the pazopanib and sunitinib treatment groups in time spent in TWiST varied by –11 days to 43 days depending on the weighted utility value of TOX and REL.

All but three of the 25 weighted scenarios were in favour of pazopanib over sunitinib, although fewer than half reached statistical significance. And the researchers note that as the benefit of pazopanib was less than 10% of the median overall survival the “magnitude of that difference tended to be rather small”.

When TOX was adjusted to include grade 2 and more severe toxicities, patients given pazopanib had 20 days fewer in TWiST than their sunitinib-treated counterparts and again threshold analysis generally favoured pazopanib, with a difference of between –11 and 33 days.

“At present, there are no guidelines for the interpretation of Q-TWiST scores with respect to PFS”, observe Jennifer Beaumont and co-investigators.

“[H]owever, such guidelines, if established, could potentially prove useful in settings such as this, where little survival difference is anticipated and the primary concerns lie with balancing disease symptoms and treatment toxicities”, they conclude.

Reference

Beaumont JL, Salsman JM, Diaz J, et al. Quality-adjusted time without symptoms or toxicity analysis of pazopanib versus sunitinib in patients with renal cell carcinoma. Cancer 2016; Advance online publication 27 January. DOI: 10.1002/cncr.29888

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