IGCS 2012 - Vancouver, BC, Canada

GOG 209 study: optimal management of advanced endometrial cancer

Professor David Miller – University of Texas Southwestern Medical Centre, Dallas, USA

David, you’ve been talking about optimal management of advanced endometrial cancer. Endometrial cancer is, in some ways, treated very well by surgery but you’ve got a minority of patients who have advanced disease, what have you been doing with them?

Well, that is correct and we are fortunate that we can find the disease early, it can be treated usually successfully with surgery, occasionally some adjuvant therapy with radiation therapy, but our issue for today was advanced endometrial cancer because that does account for 20-30% of patients. We’re moving more towards chemotherapy; we’re exploring biologic therapies and we’ve had some recent progress that we wanted to share with the group.

In fact you’ve been giving results about the GOG 209 study, haven’t you?

Yes, yes.

What came up?

Well, in GOG 209 we were looking for trying to simplify treatment of advanced endometrial cancer. We had a very active three drug regimen with cisplatinum, doxorubicin and paclitaxel which was our most active regimen to date, had shown a clear survival advantage over other regimens, but it was a toxic therapy and, as we move into the area of targeted therapy, we also knew that this three drug regimen did not lend itself to combinations with targeted therapy. So we used another regimen called carboplatinum paclitaxel that’s commonly used for ovarian cancer and that we had every reason to suspect would be active also against endometrial cancer. So we did a very large randomised trial done by the Gynaecologic Oncology Group; it was reported at the Society of Gynaecologic Oncology this spring and what that study showed was that the two drug regimen was as good as the three drug regimen in terms of activity against the cancer, overall survival whereas it was less toxic. The less toxic part is important because that will then allow us to hopefully add on targeted therapies or biologic therapies to combine with that carboplatinum paclitaxel so we can try and push things forward a little bit more.

Let me ask you about the immediate clinical implications of the findings from GOG 209 then, what are they?

Again, the immediate findings are one, is that we can get as much advantage of a one-day regimen that can be given at an outpatient office with less neurotoxicity than our prior three drug regimen that took two days to administer and had a higher neurologic toxicity to it.

Now in looking at optimal management of advanced endometrial cancer, you’re also trying to define the role of radiotherapy and also looking eventually to targeted therapies, bevacizumab and so on. What have you got in the pipeline for us and what are your feelings about them?

We’ve slowly been defining, over the years, the role of radiation therapy, particularly in advanced endometrial cancer and we’re looking forward to the results of a study called GOG 258 where we’re looking at comparing chemotherapy with or without radiation therapy. We’ve done a prior study where we had chemotherapy versus radiation, chemotherapy was a little bit better, neither was great. We then did a subsequent study which showed that we could sequence the two treatments but that too was toxic; we could give chemotherapy after the radiation. And so again, in an effort to try and simplify treatment and get the most value out of that treatment, the GOG 258 patients will receive carboplatinum, paclitaxel. One group will just get chemotherapy; the other group will get radiation therapy directed against the known site of tumour, of cancer, followed by three more cycles of carboplatinum and paclitaxel. So that study is about two-thirds of the way done, it has a couple more years to run but it should be treatment defining when we get those results.

It’s all a question of the toxicity and effectiveness but when are we going to find out?

It will probably be about two years. Two years from now.

In the meantime, you’re looking at targeted therapies, what are you doing on that front and what are your hopes?

Well, we have our targeted therapy that’s furthest along in terms of development right now is bevacizumab. It’s also a drug that’s been used in ovarian cancer and it has shown activity as a single agent in very advanced endometrial cancer. We recently completed a study called 86P where we combined carboplatinum paclitaxel with bevacizumab, compared that with carboplatinum and paclitaxel and another agent called temsirolimus and then a third arm in the study was carboplatinum, ixabepilone and bevacizumab. That study completed a few months ago. Those results are pending and we have recently got approval to move on with our next trial in this 86 series of combining chemotherapy with biologic agents in advanced endometrial cancer and that will be carboplatin paclitaxel with metformin.

Now that’s interesting to hear. With metformin what are your hopes there and why are you using metformin?

Well metformin, that’s one of the reasons that you always looked back at your medicines to see what their effect is besides that which you had originally used the medicine for. You may know that metformin is used as a diabetes medicine. Well, when they looked back at the experience with metformin they noticed that patients who took metformin seemed to get a lot less cancer. Then they started looking at how the drug might work, it did have some anti-angiogenic properties. Then we’ve had some smart scientists who in the lab used it against endometrial cancer cells, saw activity, and it’s generic, it’s cheap, so we’re very much looking forward to starting that study.

It seems that you’ve got a lot of successes so far in endometrial cancer.

We keep plugging away.

How do you sum this up for the busy doctor though? What should doctors think about doing with their patients on a day to day basis?

Right now the standard of care for advanced endometrial cancer is first surgery, surgery to remove gross residual endometrial cancer that’s there, remove lymph nodes, remove intra-abdominal metastases, if that can be done safely. If the disease is confined locally, usually in the pelvis, then the standard of care is still probably radiation therapy followed by some chemotherapy and then we continue to refine and add to those chemotherapies. Really, what the state of the art chemotherapy right now for advanced endometrial cancer is carboplatin and paclitaxel.

David, thanks for giving us those pearls of wisdom and all the latest information here on ecancer.tv.

Thanks for having me.