Masitinib Shows Survival Benefits For GIST

Masitinib Shows Survival Benefits For GIST Masitinib shows a promising benefit–risk ratio in the treatment of advanced gastrointestinal stromal tumour

medwireNews: Masitinib extends progression-free survival beyond 3 months in patients with gastrointestinal stromal tumour (GIST) who have failed to respond to imatinib, an efficacy analysis shows.

Further analysis also indicated that patients treated with masitinib followed by post-progression addition of sunitinib, the current standard of care, had a significant survival advantage over those treated solely with sunitinib. The benefit that was sustained over 26 months of follow-up, despite both drugs being associated with a similar risk of disease progression.

“The salient point demonstrated by this study was that adding masitinib to the [armamentarium] of drugs used to treat GIST generates a clinically relevant survival benefit, regardless of the complexities inherent to assigning a specific [overall survival] contribution to a drug in the setting of effective subsequent therapies”, the researchers comment in the Annals of Oncology.

They randomly assigned 44 patients with imatinib-resistant GIST to receive masitinib 12 mg/kg daily or sunitinib 50 mg/day 4 weeks on and 2 weeks off until progression, intolerance or refusal.
Patients treated with masitinib, a highly selective tyrosine kinase inhibitor, met the prespecified primary efficacy criterion of a median progression-free survival of more than 3 months, achieving a median of 3.71 months.

Additionally, over a median follow-up period of 14 months patients receiving masitinib experienced significantly fewer severe adverse events (52 vs 91%), non-haematological grade 3 and 4 events (48 vs 76%), nonfatal serious events (13 vs 33%) and adverse events leading to dose reduction (22 vs 38%). Nausea/vomiting was the only unwanted effect that occurred more frequently among masitinib-treated than sunitinib-treated patients.

“The better safety profile of masitinib when compared against sunitinib can be considered as clinically relevant because transition from imatinib to sunitinib can present a challenge for many patients”, note the researchers Axel Le Cesne, from Institut Gustave Roussy in Villejuif in France, and colleagues.

“Consequently, the use of dose reduction or temporary dose interruption is often necessary to manage sunitinib’s side-effects, the incidence of which tends to increase slightly over time. Hence, there remains an unmet medical need in terms of safety that is addressed with masitinib”, they add.

In secondary comparative analyses, patients treated with masitinib followed by sunitinib if necessary had a significant 73% lower risk of dying than patients treated solely with sunitinib as second-line treatment. The median overall survival was not reached in the patients treated with masitinib, but was estimated to be more than 21.2 months, compared with 15.2 months for patients treated with sunitinib.

This survival advantage was sustained, with masitinib associated with a 60% reduced risk of death at a median follow-up of 26 months, and a 12.4 months survival advantage over sunitinib.

“Encouraging long-term median [overall survival] data for the masitinib treatment arm coupled with better safety of masitinib when compared against sunitinib indicate a positive benefit–risk ratio”, the team concludes.

Reference

Adenis A, Blay J-Y, Bui-Nguyen B, et al. Mastinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: A randomized controlled open-label trial. Ann Oncol 2014; First published online 25 July. doi:10.1093/annonc/mdu237

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