Phase III clinical trials at ASCO 2010

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Published: 20 Jul 2010
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Prof Patrick Schöffski - Catholic University Leuven, Belgium
Prof Schöffski talks about two phase III trial results presented at ASCO 2010. The first of these demonstrated that the tyrosine kinase inhibitor vandetanib increases progression free survival in patients with advanced metastatic medullary thyroid carcinoma and the second found that a combination of platinum salt and paclitaxel is an effective and inexpensive treatment for elderly patients with non-small cell lung cancer. Prof Schöffski goes on to outline a phase II study his group is currently working on, looking at eribulin as a treatment for patients with advanced metastatic sarcomas.

ASCO 2010 Annual Meeting, 4—8 June 2010, Chicago

Interview with Professor Patrick Schöffski (Catholic University, Leuven, Belgium)

Phase III clinical trials at ASCO 2010

Thank you so much for coming and talking here on ecancer TV.

Now you are one of the most passionate advocates of phase III trials and I think it’s nice to see some big phase III trials being presented here in ASCO. There are more and more educational sessions every year and certainly it’s difficult to find a lot of translational science, compared to ACR, but some really quite big things this time. Obviously the melanoma has got front page and so on but you’ve been involved with several other studies, this medullary thyroid cancer, tell me about that.

Well, there are a number of randomised phase III trials which I find quite amazing at this meeting. And interestingly not all of them are featured in the big plenary sessions so you have to discover them at this meeting. One trial that I find quite interesting, and I was indeed personally involved in that trial, is a randomised phase III trial using Vandetanib, which is a tyrosine kinase inhibitor, in patients with advanced metastatic medullary thyroid carcinoma, which is a rare disease so not a lot of companies have explored this field in the past. But here we see major progress in terms of progression free survival in a randomised trial comparing Vandetanib against placebo. And we should not forget that this is an indication for which no standard treatment is established and nothing has been studied in the past decades. So this is a study that I’m quite impressed about; there are, of course, always issues regarding trial design.

Especially placebo.

Placebo is certainly an option, but there was cross-over in this trial so I don’t think this is a major issue. The major issue in medullary thyroid carcinoma is the fact that this can be a very slowly progressing disease in patients and patients may have a median survival of ten years or even fifteen years. So it’s absolutely critical to try to enrich such a trial with patients who are clearly progressing before they get onto the study, because in that disease we have a biochemical marker that we can use for exploring anti-tumour effects like a surrogate endpoint which is calcitonin and CEA which have frequently been used in clinical research in this disease. But we should also correlate the results, of course, with patient benefit which is difficult to do if the endpoint of the trial is progression free survival.

Tell me about the numbers on Vandetanib in that arm? What sort of progression free survival for that tumour?

There was roughly a doubling in progression free survival and the authors reported major benefit in terms of patient wellbeing, symptomatology of the patients and so on.

And calcitonin suppression.

And an impressive drop in calcitonin. So this is a very interesting trial and it could potentially be practice changing.

Good. Second trial?

The second trail I’m very excited about is a study that was featured in the plenary session. A trial in an elderly patient population in non-small cell lung cancer inoperable disease – patients who do not qualify for local treatments like surgery or radiotherapy anymore. This is a patient population that has been neglected in the past and here the colleagues from France have tried to compare two standard single agents in this elderly population versus a combination of a platinum salt and Paclitaxel. And interestingly, for the first time, at least to my knowledge, a combination was found to give better results than the single agents. And the combination that was used is based on very traditional agents that we are using for decades now, so it’s likely cost-efficient because we are not talking about very new and very expensive drugs. So I’m very happy to see at this year’s ASCO that we see the maturation of big randomised phase III trials in elderly populations, which is of course very relevant considering the epidemiology of cancer.

Your own group, of course, will be working in a number of areas here and presenting?

We have a number of abstract submissions to this year’s meeting. The one that might be most interesting to you is a phase II study that I performed with the EORTC Soft Tissue and Bone Sarcoma Group in patients with advanced metastatic sarcomas with a new marine compound which is called Eribulin which comes from a Japanese company. It belongs to the broader family of dolastatin analogues; it has been studied in breast cancer and a big randomised phase III trial is presented here at this meeting as well in breast cancer. We were the first to study this compound in four different subsets of soft tissue sarcomas, so we had four different parallel phase II studies combined in one protocol and we were studying the efficacy of this compound in leiomyosarcomas, in liposarcomas, in synovial sarcomas and in a mixed bag of other soft tissue sarcomas. And interestingly we saw objective responses, which is not often the case with new drugs in the soft tissue and bone sarcoma world. These patients were all pre-treated with at least an entrocycline and usually also with Ifosfamide, so a heavily pre-treated population. And we saw objective responses in two more types like dedifferentiated liposarcomas, in epithelioid sarcomas and in leiomyosarcomas, both uterine and non-uterine leiomyosarcomas. And all these tumour types are very difficult to treat, do not respond very well to conventional chemotherapy and we are still looking for alternative drugs for these diseases.

Had you got biomarkers for these?

Unfortunately we have not been able to establish biomarkers as of yet, but luckily we collected about 100 tumour blocks from more than 100 patients in this trial and we are just finalising the contracts to perform the translational research in labs in both Leuven in Belgium and in Rotterdam in the Netherlands.

Fantastic, that’s very good. Patrick, thank you very much indeed for coming, I really appreciate you giving your time and telling us about your hits from ASCO. I appreciate it.