Prolonged adjuvant imatinib boosts survival with high-risk GI stromal tumors

Last Updated: 2020-06-05

By Will Boggs MD

NEW YORK (Reuters Health) - Receiving adjuvant imatinib for three years rather than just one improves survival in patients with high-risk gastrointestinal stromal tumors (GIST), according to 10-year follow-up of the SSGXVIII/AIO randomized clinical trial.

"Approximately half of deaths (from any cause) could be avoided with the longer duration of adjuvant imatinib during a median of 10 years of patient follow-up," Dr. Heikki Joensuu of Helsinki University Hospital, in Finland, told Reuters Health by email. "This magnitude of benefit was perhaps unexpected, and a positive surprise."

At both the 54-month and 90-month follow-up analyses, overall survival was significantly longer in the three-year imatinib group than in the one-year group.

Dr. Joensuu and colleagues now present the results of an analysis that took place when the last patient entered reached 10 years of follow-up after the randomization date. The findings, in JAMA Oncology, were published to coincide with a presentation at the virtual annual meeting of the American Society of Clinical Oncology.

The intention-to-treat (ITT) group consisted of 198 patients in the three-year imatinib group and 199 patients in the one-year imatinib group. The efficacy population (177 and 181 patients, respectively) excluded those who did not have GIST at tumor central pathology review or who had metastases removed in addition to the primary tumor at laparotomy.

In the ITT population, 5-year and 10-year relapse-free survival (RFS) estimates were 71.4% and 52.5%, respectively, in the three-year group versus 53.0% and 41.8%, which reflects a 34% lower risk of relapse with extended treatment (P=0.003).

In the efficacy population, the 10-year RFS estimates were 52.4% in the three-year group and 44.2% in the one-year group, a 30% reduction in the risk of relapse (P=0.02).

Overall survival at 5 and 10 years was also significantly greater in the three-year group (92.0% and 79.0%, respectively) than in the one-year group (85.5% and 65.3%) in the ITT group. In the efficacy group, it was 81.6% and 66.8% at 10 years (P=0.003).

These differences translate into a 45% reduced risk of death in the ITT group and a 50% reduced risk of death in the efficacy group associated with three years of adjuvant imatinib treatment.

In an exploratory analysis, most patients in each group survived at least five years after the date of GIST recurrence (66.9% in the three-year group and 60.8% in the one-year group).

Cardiac events and second cancers occurred with similar frequency in the two groups.

"The National Comprehensive Cancer Network (NCCN) of the U.S. guidelines recommend postoperative imatinib for at least 3 years when the risk of GIST recurrence is considered high," Dr. Joensuu said. "Similarly, the European Society for Medical Oncology (ESMO) guidelines recommend adjuvant imatinib for 3 years for patients with a significant risk for GIST relapse after surgery. These recommendations were influenced by the prior analyses of the SSGXVIII/AIO trial. The current long-term follow-up results from the trial provide further support to these recommendations."

"We do not know whether longer than 3-year durations of adjuvant imatinib are superior to 3 years of adjuvant imatinib," he said. "The 2 randomized studies that are comparing longer durations (either 5 or 6 years of adjuvant imatinib) to 3 years of imatinib are critically important."

Dr. Hong Zhou of Tongji Medical College, Huazhong University of Science and Technology, in Wuhan, China, who recently studied adherence to adjuvant imatinib therapy in patients with GIST, told Reuters Health by email, "Adjuvant imatinib delays recurrence in patients at high risk of relapse for GIST, but we still do not know how long it should be given. It seems that it is safer to continue imatinib than to stop it. However, prolonging adjuvant therapy can increase toxicity and costs."

"With regard to adverse reactions, similar numbers of cardiac events were recorded in the groups," said Dr. Zhou, who was not involved in the research. "These findings give us some support for prolonged imatinib therapy."

"Another question is whether prolonged imatinib exposure would increase the probability of secondary resistance," Dr. Zhou said. "We still do not get an answer from the study. In my opinion, individualized regimens based on risk-stratification, mutations, and contributing factors are an optimal alternative."

Novartis Oncology funded the study, and of Dr. Joensuu's coauthors reports financial ties to the company.

SOURCE: https://bit.ly/2A61FQz JAMA Oncology, online May 29, 2020.