Mesothelioma was previously known as a cancer that is resistant to chemotherapy. That knowledge changed in 2004 when the combination of pemetrexed disodium (Alimta) and cisplatin demonstrated a survival advantage over cisplatin alone.
This data, which resulted from a large randomized study, paved the way for pharmaceutical companies to become interested in researching and developing treatment options for what was previously thought to be a recalcitrant disease.
Today, rather then telling patients to “go home and get your affairs in order,” oncologists can provide patients a wide array of treatment options, whether the patient is newly diagnosed, has just experienced a recurrence, or even after they have been treated with several prior regimens.
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Outlined as follows are the highlights of some promising new clinical trials for the treatment of mesothelioma. The listing below is not comprehensive and should only to be used as a reference guide as every case is different.
Radiation
One treatment for mesothelioma is administering specialized forms of radiation therapy before or following a surgical procedure. Recently, a small trial using intensity-modulated radiation therapy (IMRT) prior to an extrapleural pneumonectory (EPP) demonstrated a 50% increase in survival over historical controls.
A randomized trial is now in the planning stages to confirm these results in a larger patient population.1 It is anticipated that more trials will develop over the next few years that examine the role of IMRT, perhaps in advance of a pleurectomy decortication (PD).
There are other trials currently under review by the institutional review board that will look at IMRT following either an EPP or PD. It is anticipated that a large number of institutions will participate in these studies. Though progress is being made, there are still many unanswered, basic questions in the search for optimizing a surgical approach to malignant mesothelioma and further research is needed.
A randomized trial of a PD versus combination PD with photodynamic therapy (PDT) has recently commenced following an initial, single-center, nonrandomized trial that reported a significant increase in overall survival, including patients with advanced disease.2 PDT is the use of light-sensitizing PHOTOFRIN® (porfimer sodium) [KM1] that is injected prior to the surgical procedure after which a light source is applied to sterilize the surgical bed prior to closure following a PD. Photophrin has been granted orphan drug status in mesothelioma.
Immunotherapy
Another trial that is important to mention uses a vaccine (CRS207) prior to treatment with Alimta and cisplatin. Patients receive two doses of the vaccine followed by standard therapy and then at the conclusion of therapy—and if they are stable or responding, patients will receive additional doses of the vaccine.
This trial has reported a 69% durable response in a small number of patients. Following an interim analysis of a small cohort of patients, a trial is now underway to confirm these results which should lead to a randomized trial.3
Patients who respond to or are stable following treatment with Alimta and cisplatin are also eligible for defactinib, an agent targeting cancer stem cells with the goal of lengthening the time to relapse, or perhaps—in the best case scenario—preventing relapse altogether. This is a global trial with over 25 centers participating.
In the second-line setting (for patients who have had a recurrence following first-line treatment), immunotherapy appears to have taken the lead with a multination, placebo-controlled trial of the drug tremelimumab. In melanoma, this agent has induced durable responses and, so far, has shown promise in mesothelioma treatment.
The National Cancer Institute’s new drug SS1P is also worthy of mention in this listing. SS1P is an immunotoxin that uses mesothelin (a protein) to gain entry into the cell. Early phase 1 studies have demonstrated positive results in patients with advanced disease who had failed multiple prior treatments, and a phase 2 study is currently underway.4
A full list of mesothelioma clinical trials can be found at curemeso.org/trials. Clinicians are strongly urged to refer patients to clinical trials in mesothelioma, as they are known to expedite research progress.
References
- Cho BC, Feld R, Leighl N, et al. A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the “SMART” approach for resectable malignant pleural mesothelioma. J Thorac Oncol. 2014;9(3):397-402.
- Friedberg JS, Culligan MJ, Mick R, et al. Radical pleurectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma. Ann Thorac Surg. 2012;93(5):1658-1665.
- Hassan R, Antonia SJ, Grous JJ, et al. CRS-207 vaccine plus chemotherapy as front-line treatment for subjects with malignant pleural mesothelioma (MPM). J Clin Oncol. 2013;31:(suppl; abstract TPS7607[KM2] ).
- Hassan R, Sharon E, Thomas A, et al. Phase 1 study of the antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front-line therapy of pleural mesothelioma and correlation of tumor response with serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125. Cancer. 2014 Jul 2. [Epub ahead of print]
