Bevacizumab in Malignant Pleural Mesothelioma

Transcript:

Mark A. Socinski, MD: So in keeping with the same theme, we saw another antibody that’s been a part of our practice, bevacizumab, for years in nonsquamous non-small cell lung cancer, a very interesting trial from the French, the Mesothelioma trial, in which there was a clear survival advantage. Mary Jo, do you want to walk us through that?

Mary Jo Fidler, MD: It was a randomized trial of standard chemotherapy for mesothelioma with cisplatin and pemetrexed and the randomization was to add bevacizumab. And the study met its survival endpoint with a median survival reaching over the one year mark. I consider it a positive trial and I would use bevacizumab in this setting. I find it interesting for a couple of reasons. One is its movement in the disease that hasn’t had a lot of progress in several years.

Mark A. Socinski, MD: Well, much like squamous, right?

Roy S. Herbst, MD, PhD: Yes.

Mary Jo Fidler, MD: And a second thing, most of the non-small cell lung cancer data with bevacizumab, if it’s helping, it seems to be helping when you add it to a taxane backbone. Maybe there’s some antigenic synergism with the taxanes, but the data not including the taxane has been less impressive with pemetrexed in the European AVAIL trial. So bevacizumab reached its endpoint and it may be that the angiogenic pathway is much more important in mesothelioma.

Mark A. Socinski, MD: Is this an advance, Naiyer, in your opinion?

Naiyer Rizvi, MD: Absolutely! Mesothelioma is such a tough disease to treat, and I think that having a phase III trial that met its survival endpoint is very real and I think it changes practice.

Mark A. Socinski, MD: I don’t know if they reported what percentage of the mesothelioma population would be eligible to receive bevacizumab. There are lots of reasons not to give bevacizumab.

Geoffrey R. Oxnard, MD: Overall survival was more impressive though in this phase III trial than in the last phase III trial, the Vogelzang trial. I’m not quite sure why that was. Everyone did better.

Mark A. Socinski, MD: That may be that if you exclude half your patients it may be the better patients that we’re looking at. But I don’t remember that number.

Roy S. Herbst, MD, PhD: And the tissue type, for example.

Geoffrey R. Oxnard, MD: Histologic subtype is a key biomarker, right. I do wonder if pemetrexed maintenance alone might be a good enough therapeutic option for mesothelioma. If you look at the Kaplan-Meier curves, a lot of the difference was after the six cycle time point when those on bevacizumab maintenance did well and those without maintenance therapy on the control arm did less well. So there’s a study looking at a cisplatin/pemetrexed with or without pemetrexed maintenance for mesothelioma in the CALGB Alliance that may move the bar in a similar way.

Roy S. Herbst, MD, PhD: Are there any other genetically targeted drugs for mesothelioma?

Naiyer Rizvi, MD: PI3 kinase has been explored.

Geoffrey R. Oxnard, MD: mTOR inhibitors have been unsuccessful.

Mark A. Socinski, MD: We’re involved in a nintedanib trial in mesothelioma, kind of the same design as the bevacizumab trial, plus/minus. It’s a phase II study.

Geoffrey R. Oxnard, MD: A FAK inhibitor I’ve seen. Given how many negative trials there have been, it is impressive that this one succeeded.

Mark A. Socinski, MD: Getting back to Geoff’s point, do the panelists typically practice maintenance therapy in their mesothelioma patients? I’m kind of a four cycle guy and they either respond or they don’t; then I give them a break from therapy. We have the Alliance trial open, so we try to put people on that trial to get some data, but I just wonder what other people are doing.

Roy S. Herbst, MD, PhD: Issue four cycles and watch, then think about surgery if they’re a candidate for a pleurectomy, or dare I say it, an extrapleural procedure.

Mark A. Socinski, MD: Don’t say it.

Roy S. Herbst, MD, PhD: I haven’t done one of those since I left Boston. But then you look for trials. Immunotherapies actually had some headway here.

Mark A. Socinski, MD: We’ll get back to that.

Transcript Edited for Clarity

Geoffrey R. Oxnard, MD: We’re all lung cancer docs but in every other cancer you don’t stop chemotherapy. I don’t stop chemotherapy in mesothelioma. If they get toxic, you drop the platinum and then continue the chemotherapy just like for breast cancer and for colon cancer and other cancers.