Adjuvant imatinib beneficial for high-risk gastrointestinal stromal tumors
MADRID — Adjuvant treatment with imatinib improved outcomes among patients with high-risk gastrointestinal stromal tumors, according to final results of a randomized phase 3 trial presented at the European Society for Medical Oncology Congress.
At 10 years, results showed improved imatinib failure-free survival, OS and RFS with imatinib compared with no adjuvant therapy.
Paolo G. Casali, MD, medical oncologist and head of the adult mesenchymal tumor unit at National Cancer Institute in Milan, Italy, and colleagues began their open-label, multicenter study in 2004.
The analysis — conducted at 112 hospitals in 12 countries — included 908 patients who underwent R0-R1 surgery for localized, intermediate-risk or high-risk gastrointestinal stromal tumors.
Casali and colleagues randomly assigned 454 patients to 2 years of adjuvant therapy with the tyrosine kinase inhibitor imatinib, administered in 400-mg daily doses. The other 454 patients received no further therapy.
Imatinib failure-free survival served as the primary endpoint. Secondary endpoints included RFS, relapse-free interval, OS and toxicity.
Results of interim analyses were published in 2015.
At ESMO, Casali reported final outcomes data, based on median follow-up of 9.1 years.
Overall, researchers reported 5-year imatinib failure-free survival rates of 87% in the imatinib group and 83% in the control group (HR = 0.87; 95.7% CI, 0.65-1.15). Investigators projected 10-year rates at 75% in the imatinib group and 74% in the control group.
Imatinib-treated patients achieved higher rates of RFS at 5 years (70% vs. 63%) and 10 years (63% vs. 61%; HR =0.71; 95% CI, 0.57-0.89), as well as higher rates of OS at 5 years (93% vs. 92%) and 10 years (80% vs. 78%; HR =0.88; 95% CI, 0.65-1.21).
An analysis of the 526 patients with high-risk gastrointestinal stromal tumors as determined by local pathology showed higher rates of imatinib failure-free survival (69% vs. 61%) and RFS (48% vs. 43%) for imatinib-treated patients. Although these differences did not reach statistical significance, the trends were consistent with results of a previous trial that showed a sustained small but statistically significant long-term OS benefit for patients with high-risk gastrointestinal stromal tumors treated with 3 years adjuvant imatinib.
On the contrary, results of this study should discourage the use of imatinib for patients with low-risk gastrointestinal stromal tumors, Casali said.
In addition, initial TKI failure-free survival is a tentative surrogate endpoint that may be worth exploring as part of molecularly targeted therapy of solid cancers.
“Of course, it would be best if we had overall survival as an endpoint,” Casali said. “But, as long as this is an aggressive disease, we need to use surrogate endpoints, and imatinib has been proven to extend survival.” – by Chuck Gormley
Casali PG, et al. Abstract LBA55. Presented at: European Society for Medical Oncology Congress; Sept. 8-12, 2017; Madrid.
Disclosures: Novartis funded this study. Casali reports research funding from Amgen, Bayer, Eli Lilly, Daiichi Sankyo, Epizyme, Novartis and PharmaMar; advisory roles with Bayer, Blueprint, Eisai, Eli Lilly, Merck Sharpe & Dohme, Merck Serono, Nektar Therapeutics, Novartis, Pfizer and PharmaMar; and honoraria from Bayer, Novartis, Pfizer and PharmaMar. Please see the abstract for a list of all other researchers’ relevant financial disclosures.