Zoptarelin no better than doxarubicin for second-line advanced endometrial cancer

Published: 2 Jun 2018

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Dr David Miller - The University of Texas Southwestern Medical Center

Dr Miller speaks with ecancer at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting about the phase III ZoptEC trial of zoptarelin, a doxarubicin-LHRH conjugate, versus doxarubicin alone for patients with advanced endometrial cancer who had not responded or relapsed after first-line therapy.

He describes how, contrary to phase II indications, zoptarelin had no effect on any endpoints, and the trial was negative.

The ZoptEC trial was a randomised phase III trial of a new agent, zoptarelin, compared to a traditional treatment, doxorubicin, for advanced recurrent endometrial cancer in patients who had previously failed platinum and taxane chemotherapy. Zoptarelin is a very interesting drug because it is a conjugate of doxorubicin bound to an LHRH molecule that binds to LHRH receptors which are found in many reproductive cancers. Not so much in normal tissue but particularly in endometrial cancer about 80% of endometrial cancers express this receptor. So this drug was developed, phase II trials had suggested that activity for zoptarelin in advanced recurrent endometrial cancer. So the company was interested in getting this drug registered for endometrial cancer because, as you may be aware, we only have two drugs that have been approved for endometrial cancer so there’s a significant clinical need for approved therapies. So we launched this randomised trial of the zoptarelin versus regular doxorubicin in the advanced recurrent endometrial cancer population.

Unfortunately zoptarelin was no better than doxorubicin. The response rate for the zoptarelin was 12%, it was 14% for the doxorubicin. The progression free survival for both drugs was 5 months. The overall survival for both drugs was 11 months with no significant difference. The toxicities were mainly hematologic but, again, no significant difference in terms of hematologic toxicity or even cardiac toxicity which is one thing that we had hoped to significantly reduce.

So the important message for this study is, one, it shows that even if you have a very exciting targeted therapy you need to do the heavy lifting, the randomised phase III trial to make sure that what you think is an advance is actually going to help patients. Unfortunately it did not.

Are there any plans to see what could be done to understand why the addition of the LHRH didn’t improve outcomes or go back and try a different conjugate?

Well, it’s a very small company and they, unfortunately, don’t have the means to further develop this drug. So it’s my understanding that no further development will occur.

Negative results are still results.

And they’re important because, for example, doxorubicin remains the standard of care second line cytotoxic chemotherapy for endometrial cancer and it probably is the bar that some new agent is going to have to exceed.

Until that day comes I think that’s all there is to say for zoptarelin then.

Unfortunately.