Imatinib alternating with regorafenib compared to imatinib alone for the first-line treatment of advanced gastrointestinal stromal tumor: The AGITG ALT-GIST intergroup randomized phase II trial.

BACKGROUND

To determine if an alternating regimen of the tyrosine kinase inhibitors imatinib and regorafenib improved outcomes in patients with advanced gastrointestinal stromal tumors.

METHODS

ALTGIST (NCT02365441) was a randomized phase II study of standard treatment of imatinib (Arm A) compared with an experimental alternating regimen of imatinib and regorafenib (Arm B). Primary outcome was best objective tumor response (OTR) at nine months.

RESULTS

Seventy-six eligible patients (Arm A 36, Arm B 40) enrolled were evaluable. Median follow-up was 46.0 months (range 6.5-64.6). Best responses and OTR were similar at 9 months. Eighteen (50.0%) Arm A patients and twelve (30.0%) Arm B patients discontinued treatment due to progressive disease. No Arm A patients stopped protocol therapy due to unacceptable toxicity, with 12 (30.0%) stopping in Arm B. Twelve (33.2%) Arm A patients and 12 (30.0%) Arm B patients experienced at least one serious adverse event, mostly grade 3. Secondary endpoints of PFS at 1 and OS at 1 year were not statistically different.

CONCLUSIONS

Alternation of imatinib and regorafenib did not impact on 9 months objective response nor on the secondary objectives of PFS and OS. Patients in the alternating arm experienced more toxicity and protocol discontinuations.

CLINICAL TRIAL REGISTRATION: NCT02365441.