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Primary GIST: Duration of therapy with adjuvant imatinib

DR LOVE: What do we know about the optimal duration of adjuvant therapy with imatinib?

DR BLANKE: We’re in a quandary because we don’t know the correct duration. In the Phase III trial comparing imatinib to placebo, patients received one year of treatment, but there was a fairly high relapse rate after that year ended (DeMatteo 2007).

Two European trials are ongoing, one of which is evaluating zero versus two years of imatinib and the other is comparing one year to three years.

I believe that longer will be better. I would like to see an intermediate duration versus lifelong administration, but that’s not popular in the adjuvant setting and probably will never be done. ACOSOG is trying to develop a duration question, but it is difficult because we have no data to guide us.

If we find out that three years is better than one, do we compare three to five, which doesn’t seem that different, or to 10 years or even a lifetime?

We have positive trial data for one year of therapy, but we’re seeing that the drug is being continued beyond that. It’s hard to argue with that, but at the same time, we can’t support it with any data, either.

DR LOVE: Are you worried about complications from administering imatinib for a prolonged period in an adjuvant setting, when patients may be cured and live a long time?

DR BLANKE: I’m not worried about that. We have a lot of CML data, and we’re now publishing our seven-year follow-up from the metastatic GIST trial (Blanke 2008a). We don’t see long-term complications in these patients, so that’s not a big issue. However, it is expensive and it is associated with minor toxicities. Those are more realistic issues.

The Europeans feel that since we can administer salvage treatment when patients relapse, why commit them to lifelong imatinib? Rather, we can treat them for a short duration, delay the time to recurrence, and then administer it to them again later, in cyclical bursts.

It’s hard to argue with that, except that it’s not a particularly effective argument with patients. They don’t like to hear that we’re certain their disease will recur if we don’t administer imatinib continuously but we’ll only restart it when that happens.

I decide by examining the patient’s risk. Patients with small bowel tumors with 50 mitoses I tend to allow to stay on the drug. Patients with 26-cm tumors I tend to keep on the drug.

However, I usually tell them that they will stay on it for three years, because that is the longest safety data we have in the adjuvant setting and I am not comfortable continuing it for much longer than that.

I am now approaching that three-year point with patients, and they are asking to stay on it longer. I do not believe many clinicians are administering it for the longer duration, although Ron DeMatteo does.

Although he conducted the study with a one-year duration, off study he keeps patients on it longer because, I assume, he also believes it is a relatively systemic disease.