Cabazitaxel in male patients with metastatic germ cell tumors pretreated with CABA-GCT chemotherapy

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Alicia Morgans: Hello, my name is Alicia Morgans and I am a GU Medical Oncologist at the Dana-Farber Cancer Institute. I’m very happy to have here with me today, Dr. Giulia Baciarello, who is a GU medical oncologist in Milan, Italy, at the National Cancer Institute there. I am delighted to speak to her today about a presentation she gave at ESMO 2021, on cabazitaxel in patients with refractory germ cell tumors. Thank you very much for being here with me today, Dr. Baciarello.

Giulia Baciarello: Thank you very much Alicia. I am very happy to be here and to present this study.

Alicia Morgans: Very large. Thank you. So why not start by explaining why this study was necessary, and what the study consisted of?

Giulia Baciarello: Yes of course. So, first of all, this was an academic essay, so we made a really big effort to design it. We know germ cell tumors are a very rare disease, and even in the metastatic setting we can actually cure the vast majority of patients. When a patient relapses after the first line of cisplatin chemotherapy, we can still cure them in almost [inaudible 00:01:06] 20 to 50% of cases, depending on [inaudible 00:01:10] big criteria. However, when our patients experience disease progression after two or three lines, the prognosis is really very poor, and currently we don’t have a standard treatment in this setting.

That is why we, since we know that taxanes are active in germ cell tumors, we have given high priority to cabazitaxel, which is a second generation taxane, may have some activity in this context, with toxicity limited, especially for our peripheral neuropathy problems. . In addition, since it can cross the blood-brain barrier, we also hypothesize a potential activity on brain metastases.

We included patients who relapsed, whose tumors relapsed after two or three lines of chemotherapy, including standard taxane-based chemotherapy, and high doses, and patients with brain metastases. They received up to six cycles of cabazitaxel every three weeks. And the primary endpoint was a favorable disease rate, which we defined as a complete response or a partial response with standardized tumor markers. And we also did an exploratory analysis to assess the overall rate of disease control.

So we actually included 37 patients. More than a third of them had already received taxane-based chemotherapy, and more than a third of them had received high-dose chemotherapy. It was therefore a highly pre-treated population. And cabazitaxel induced a favorable response rate in nearly 6% of patients, while the overall disease control rate was achieved by 26% of patients.

Only four patients had brain metastases, so we could not perform an efficacy analysis on this subgroup. And at six months, nearly 20% of patients still had stable disease, while nearly 60% of them were still alive. Cabazitaxel was also safe, in fact only seven patients experienced a grade three or higher adverse event. So in fact what we have seen is that cabazitaxel is safe, but it probably has limited efficacy for dissection, especially in highly pretreated populations.

Alicia Morgans: I think this is so important to know, and interesting, of course, that this population included men who had previously had taxane chemotherapy. So of course that can also come into play. So given the tolerance, and noting that some patients, in this extremely pretreated population, have had responses, or at least stable disease, for six months, which is not always what we see in these patients, are you and the team moving this approach forward to see if it might have some effectiveness in a larger trial?

Giulia Baciarello: Now, in fact what we have seen is that, although we have achieved stable disease for a good number of our patients, it appears that this therapy, at least as monotherapy, in an unselected population, has had a fairly limited efficacy, we can use it, why not, in some patients, since even in the absence of direct comparison with other monotherapies, with a taxane, or another multidrug therapy, it seems to have a fairly similar activity and possibly limited toxicity.

I don’t think we will support another trial, especially a larger Phase II trial. We know that phase III randomized trials are quite impossible in this setting, but no, we would like to do it, at least in an unselected population.

Alicia Morgans: I think that makes sense. Especially since there is a certain interest in using certain innovative approaches, certain targeted therapies, perhaps. But, I really commend you and the team for doing this work, because germ cell tumors, when they get this advanced, are very aggressive and devastating for these patients, and have options for that need. , very clearly, not satisfied, is essential. So I appreciate that you and the team, and of course the patients, have done this.

So if you could summarize the results, what would your summary and conclusion be?

Giulia Baciarello: I think men with refractory disease still have a poor prognosis, and we still don’t have standard treatment. I think we should stop doing phase II trials, or trials in an unselected population. We need to better define what are the potential drivers of tumor progression or certain potential targeted alterations. We know that we have done other trials, particularly as you said, with targeted agents, but we have not shown any clinical activity like with TKIs or immune checkpoint inhibitors, although a good percentage of patients, especially patients with seminoma, actually expressed PDL1. So we should probably design some kind of frame trial, to better define the right therapy for each patient.

Alicia Morgans: Well I think it’s a fantastic idea, and I’m looking forward to you and the team working on it and trying to help us define biology, so that we can match that biology and understand what drives it. cancer, with the appropriate treatment. I think this is the most practical sense.

So thank you very much for doing the job, and of course, for taking the time to go through your presentation with us today, we appreciate it.

Giulia Baciarello: Thank you so much.


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