Advances in Mesothelioma Treatment: New Systemic Therapies and Clinical Trials

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• Future of Mesothelioma Treatment
• Biological Pathways and Targets
• Clinical Trial Advances
• Improving Therapy Success
• Role of Randomized Trials
• Optimistic Outlook
• Full Transcript

Future of Mesothelioma Treatment

Dr. Dean Fennell, MD, expresses optimism about the future of mesothelioma treatment. He notes an accelerating pace of development in systemic therapies for this challenging cancer. The focus is shifting toward identifying and exploiting specific biological vulnerabilities within mesothelioma cells. Dr. Fennell believes this approach will lead to more meaningful therapeutic breakthroughs in the coming years.

Biological Pathways and Targets

Research is uncovering druggable biological pathways that represent critical vulnerabilities in mesothelioma. Dr. Dean Fennell, MD, explains that these pathways can be therapeutically exploited, similar to how PARP inhibitors work in ovarian cancer or EGFR inhibitors in other malignancies. International collaborations, such as those with the Sanger Institute in Cambridge, are using genetics of drug sensitivity platforms to identify new treatment strategies. These discoveries are expected to translate into more effective clinical therapies.

Clinical Trial Advances

Master clinical trial protocols are becoming essential accelerators for mesothelioma therapy development. Dr. Dean Fennell, MD, emphasizes that these platforms allow researchers to rapidly test new treatment hypotheses. This approach reduces the time from discovery to clinical application, benefiting patients through faster access to promising therapies. The structured framework of master protocols helps avoid repetitive negative phase 2 and phase 3 trials that have historically plagued mesothelioma research.

Improving Therapy Success

The goal of modern mesothelioma treatment is to achieve higher response rates and induce apoptosis in cancer cells. Dr. Dean Fennell, MD, discusses the need for more impressive therapy success signals in clinical trials. He references the RAMES trial, an Italian study that demonstrated improved survival with ramucirumab and gemcitabine versus gemcitabine alone in relapsed mesothelioma. Such successes provide a blueprint for future trial designs and treatment combinations.

Role of Randomized Trials

Randomized controlled studies remain the gold standard for advancing mesothelioma therapy. Dr. Dean Fennell, MD, stresses that incremental improvements in cancer treatment have historically come from well-controlled randomized trials. While exceptionally powerful targeted drugs can show dramatic effects, randomization provides the necessary evidence for broader clinical adoption. This rigorous approach ensures that new treatments are both effective and reliable for patients.

Optimistic Outlook

Dr. Dean Fennell, MD, maintains a positive outlook on the future of mesothelioma treatment. He anticipates more drug approvals and better survival outcomes based on current research trajectories. The combination of biological insights, advanced trial designs, and international cooperation creates a fertile ground for progress. Dr. Anton Titov, MD, as the interviewer, facilitates this discussion on how these advances will ultimately benefit patients facing mesothelioma.

Full Transcript

Dr. Anton Titov, MD: Professor Fennell, what is the future in mesothelioma treatment? What advances could we see in the next three to five years, or maybe even at a longer horizon?

Dr. Dean Fennell, MD: I want to be optimistic. Actually, I think that we are seeing an increasing pace of development. There are aspects of biology within mesothelioma that we're beginning to see druggable. And some of these biological pathways may be really meaningful vulnerabilities.

They can be exploited therapeutically. So I would like to see more rational clinical trials. We want more impressive therapy success signals. We want to see higher response rates.

We want to see strategies that can induce apoptosis in much the same way as we have seen with PARP inhibitors in ovarian cancer or with EGFR inhibitors. I do believe that could be possible with the mesothelioma drug discovery platforms that we have.

Genetics of drug sensitivity platforms are being run via transatlantic cooperation with the Sanger Institute in Cambridge. The hope is that we will be able to identify new strategies of mesothelioma treatment that can be translated into the clinic.

So it's being ready for that. And we have platforms that allow us to readily test mesothelioma therapy hypotheses. The master clinical trial protocol becomes an accelerator for getting these ideas into the clinic and hopefully advancing their development.

I think for patients, it's good because ultimately, we should see more active mesothelioma drugs coming through. It should be much fewer negative phase 2 and phase 3 clinical trials that we have been used to seeing over and over again over the last two decades.

Dr. Anton Titov, MD: So overall, Professor Fennell, you see more progress in mesothelioma to be made from a systemic treatment perspective and the new technologies, rather than from traditional surgical and radiotherapy critical advances?

Dr. Dean Fennell, MD: One thing I must say, I think, in the long run, the most important thing is randomization. We need well-controlled randomized studies in order to be able to make incremental improvements in mesothelioma therapy.

This has been the paradigm across all of cancer as long as I can go back in literature. Cancer therapy advances have come from randomized trials. There was the exception of those remarkably powerful cancer drugs that are leveraging some vulnerability in cancer.

The randomized clinical trial is key in helping us.

Dr. Anton Titov, MD: What we have seen over the last couple of years with trials such as the RAMES trial, which I haven't mentioned. It's the Italian study, looking at ramucirumab and gemcitabine versus gemcitabine alone. This revealed again, improved survival in a relapsed mesothelioma.

Dr. Dean Fennell, MD: And more of those types of trial design is going to lead to more advances. I'm very optimistic, actually, based on what I can see in development for mesothelioma. We are going to get closer to having more approvals in the future.