The FDA recently approved nivolumab/ipilimumab for the first-line treatment of malignant pleural mesothelioma, marking the second FDA approval for this condition and the first approval in the past 16 years. In this interview, Paul Baas, MD, PhD, principal investigator of the CheckMate 743 trial (NCT02899299), on which the approval was based, speaks with Oncology Data Advisor about the benefits and tolerability of nivolumab/ipilimumab, ongoing research advances in the treatment of malignant pleural mesothelioma, and advice for oncologists treating patients with this condition.
Can you comment on the significance of the approval of nivolumab/ipilimumab for malignant pleural mesothelioma?
Paul Baas, MD, PhD: I think it's a great step forward in the treatment of patients with malignant mesothelioma. We have had a standard of care since 2004, and since then, hardly anything has changed. We have tried to improve the survival figures by adding bevacizumab––that was a French study––and it proved to give some better outcomes for these patients, but it was not accepted worldwide, so the introduction of an immuno-oncology (IO) treatment, as we have seen in melanoma and in non-small cell lung cancer, is something that has really made a huge step forward.
What adverse events are of concern with this regimen, and how are they best managed?
Dr. Baas: At first, I was a bit afraid of the combination of ipilimumab and nivolumab because pretty high doses were used in other tumor types and can give serious side effects, like diarrhea or inflammatory responses all over the body. However, the lower dosages that have been administered in this study are better tolerated in this patient population, which has an average age of 70 years. The toxicity, if you look at giving it over two years of treatment, was very manageable.
So what additional research advances look promising for patients with malignant pleural mesothelioma?
Dr. Baas: Additional research that is already ongoing focuses on the role of adding chemotherapy to IO drugs. We know from experience in lung cancer that combining chemotherapy in the first line with IO improves the outcome. There are studies ongoing, such as that with durvalumab, and the initial reports are promising. We really have to find out whether more drugs are useful in patients with mesothelioma. And how about the toxicity of chemotherapy with IO? The great advantage of IO treatment is that you can keep the chemotherapy in your pocket for later issues.
We also hope that with new research, we can identify those patients who are really the best candidates for this treatment, as well as those who are not good candidates. If we can identify patients who do not benefit from immunotherapy treatment, we don't have to bother them with it; we don't have the possible side effects or the financial toxicity and can then focus the treatment on those patients that really have a great, long-lasting response.
What advice can you offer to oncologists as they treat patients with malignant pleural mesothelioma?
Dr. Baas: My recommendation is that for the majority of patients who present with mesothelioma, one should consider a treatment with nivolumab and ipilimumab. Of course, there is an issue of cost. We know that the previous treatment of platinum with pemetrexed will now be much cheaper because pemetrexed is going out of patent. But if there is a possibility to give this IO treatment of nivolumab and ipilimumab, it's always better than the chemotherapy, especially in those who have the non-epithelioid type; in these cases, we know that chemotherapy is hardly effective. Using this IO combination, there's a huge benefit over 9.3 months median overall survival, and we still do not have the data on the tail of the curve, so maybe long survivors will be identified in the near future.
That's great. Is there anything else that you would like to add?
Dr. Baas: In October of this year, the FDA already approved the combination, and the European Medicines Agency (EMA) is currently in the process of registration approval. I think it will be accepted and can't see any reason why it would be declined. It's also better to have more options for patients. As an oncologist with a specialization in mesothelioma, I'm very happy that I can offer my patients much more now, and also do so early––in the first line––to delay the use of chemotherapy.
About Dr. Baas
Paul Baas, MD, PhD, is a Professor of Thoracic Oncology at the Faculty of Medicine of the Leiden University Medical Center and in the Department of Thoracic Oncology at the Netherlands Cancer Institute. His research focuses on the development of new therapies in the treatment of lung cancer and malignant mesothelioma. An expert in this field, he is the first author of the European Society of Medical Oncology (ESMO) Clinical Practice Guideline for malignant pleural mesothelioma.
For More Information
Clinicaltrials.gov (2020). Study of nivolumab combined with ipilimumab versus pemetrexed and cisplatin or carboplatin as first line therapy in unresectable pleural mesothelioma patients (CheckMate743). NLM identifier: NCT02899299.
Zalcman G, Peters S, Mansfield AS, et al (2017). Checkmate 743: a phase 3, randomized, open-label trial of nivolumab (nivo) plus ipilimumab (ipi) vs pemetrexed plus cisplatin or carboplatin as first-line therapy in unresectable pleural mesothelioma. J Clin Oncol (ASCO Annual Meeting Abstracts), 35(suppl_15). Abstract TPS8581. DOI:10.1200/JCO.2017.35.15_suppl.TPS8581
Zalcman G, Mazieres J, Margery J, et al (2016). Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet, 387(10026):1405-1414. DOI:10.1016/S0140-6736(15)01238-6
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.