Continuous vs intermittent imatinib treatment in advanced GIST after one year: A prospective randomized phase III trial of the French Sarcoma Group

Abstract

9006 Background: Imatinib (Im) is usually given in advanced GIST until progression or intolerance. Secondary resistance to Im is often related to the clonal expansion of clones with Im insensitive KIT mutations. Whether intermittent administration of Im may prevent the long term emergence of resistant clones is unknown. Methods: BFR14, a prospective multicentric phase III study of continuous vs interrupted imatinib treatment in advanced GIST, was initiated in June 2002. Inclusion criterias were: advanced GIST, expressing KIT or PDGFRa mutation. After 1 year of treatment with Im, patients are randomized between 1) continuous (CONT) or 2 ) interruption (STOP) of Im until progression and restart. Patients declining randomization were followed. Primary endpoint was progression free survival. Early stopping rule in case of high rates of re-progression at 3 months were scheduled after the randomisation of 14 patients (n>5) and 29 pts (n>10). Results: As of December 2003, 159 pts were included: 61% were males, 39% emales (39%), with gastric 27%, small bowel (32%), large bowel (12%), mesenteric (20%), or other primaries (9%). Metastatic sites were: liver (55%), peritoneum (35%), nodes (6%), others (19%). 13% pts experienced immediate progression. At 6 months, CR was achieved in 10%, PR in 42%, SD in 36%, PD in 6%, NE in 6% . 41 SAE were observed in 29 pts. Surgery was perfomed in 6 (4%) pts during the 1st year. As of Dec 15, 46 of the 74 (62%) candidate pts were randomized, 23 in both arms: 0 and 5 (21%) pts have a documented reprogression at 3 months in the CONT and STOP arms respectively; Im reintroduction enabled tumor control in all pts with sufficient follow-up so far. Conclusions: Although the early stopping rule on progression at 3 months was not met in the first 14 pts randomized in the STOP arm of the BFR14 trial, advanced GIST pts stopping Gleevec® experience frequent re-progression at 3 months. Supported by Grants from the Centre L.Bérard, Cancéropole Rhone Alpes and Novartis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis