Malignant pleural mesothelioma (MPM) is both rare and exceedingly difficult to treat. Current treatment options include surgery, radiation, and chemotherapy; however, of these options, only chemotherapy has been shown to confer a (modest) survival benefit. The recurrence rate with surgical resection is extremely high and offers only local control of the malignancy, with no benefit provided for spreading of the disease (metastasis). Radiation alone is also an ineffective treatment, offering purely palliative effects to help relieve patients’ symptoms.
Presently, combination therapy with the chemotherapy drugs cisplatin and pemetrexed is considered the standard of care for MPM. This regimen offers a 30% response rate and only a very mild survival benefit. Additional chemotherapy drugs that may used to treat of MPM include gemcitabine, ranpirnase, and carboplatin. One possible explanation for the poor effectiveness of chemotherapy in this disease state is the overexpression of inhibitor of apoptosis proteins (IAPs) with subsequent low apoptotic rate present in MPM, resulting in resistance to chemotherapeutic agents.
The European Lung Cancer Conference (ELCC) is a pan-European collaboration between prominent professional societies that represent thoracic oncologists, which aims to further lung cancer education, research, and clinical practice worldwide. The 2016 conference was held last month (April 13 – 16) in Geneva, Switzerland. At that conference, information about a novel treatment option for pleural mesothelioma was presented. This new treatment is known as CRS-207.
In patients who have mesothelioma, there are large amounts of the antigen associated with mesothelin, a human protein. (Antigens are substances that trigger the body’s immune response.) CRS-207 is a live, attenuated Listeria monocytogenes bacterium that has been engineered to produce mesothelin. Early studies on CRS-207 have demonstrated the treatment’s ability to confer cellular tumor-specific immunity and an anti-mesothelin response in patients with pleural mesothelioma. Additionally, CRS-207 has been shown to work in combination with chemotherapy, boosting the effects of each treatment.
The research presented at the 2016 ELCC focused on the results of a phase 1b trial that examined the effects of CRS-207, which was administered in combination with standard chemotherapy to patients with advanced stage pleural mesothelioma that could not be removed through surgery. The study, conducted at the University of California San Francisco, consisted of 38 patients. Each patient received a medication regimen that included:
- Two infusions of CRS-207 given two weeks apart;
- Up to six cycles of cisplatin/pemetrexed given three weeks apart;
- Followed by two additional infusions of CRS-207 infusions given three weeks apart.
Additional CRS-207 was then administered every eight weeks to eligible patients at follow-up as a maintenance measure, until disease progression occurred.
Results of the CRS-207 Study
After a little more than nine months – the average follow-up period for patients in this study – investigators found that 35% of participants demonstrated stable disease (no increase in tumor number or size), while 59% of patients had achieved a partial response (shrinkage of existing tumors). These results indicated an impressive 94% overall disease control rate, with a progression-free survival rate of 8.5 months. Analysis performed in participants following administration of CRS-207 confirmed the study’s preclinical hypothesis.
Side effects of CRS-207 noted in this study were minimal and included temperature spike and rigors associated with infusion administration, which generally disappeared within 24 hours. The study’s primary investigator, Dr. Thierry Jahan, noted that CRS-207 was tolerated well by the participants, and he commented on the agent’s remarkable safety profile and lack of cumulative toxicity when administered in conjunction with cisplatin/pemetrexed.
As a difficult-to-manage disease with a dearth of available treatment options, a dire need for effective mesothelioma treatment exists. The current study suggests that CRS-207 is a promising development for the patients who suffer from malignant pleural mesothelioma and their treating physicians. Additional research will need to be done to confirm the results of this latest study, but researchers, patients, and doctors are all hopeful. A randomized trial to further assess the efficacy of CRS-207 is scheduled to begin later this year.