At the moment, the first line of treatment for pleural mesothelioma consists in pemetrexed and platinum chemotherapy, two substances which have proved quite effective in keeping the disease under control. However, as mesothelioma entails a very aggressive progression and as there is currently no second line of treatment, more than 50% of patients relapse within six months after treatment cessation. The medication which has so far undergone testing as a second line of treatment was found to have a low disease control rate of under 30%. For these reasons, the average life expectancy of pleural mesothelioma patients ranges between only 13 and 15 months.
Fortunately, immunotherapy may become the standard second line of treatment for pleural mesothelioma in the future, as a recent French study discovered promising evidence supporting the efficiency of this therapy in delaying the growth of malignant tumors. The first study, known as MAPS-2, revealed that immunotherapy with checkpoint blockade can slow the growth of pleural mesothelioma tumors after relapse. Furthermore, immune checkpoint inhibitors, which are involved in this treatment, may also improve survival rate. Antiangiogenic inhibitors such as bevacizumab can also be used in conjunction with immunotherapy, as they facilitate the shrinking of the tumor.
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Numerous malignant tumors release certain proteins which prevent the immune system from fighting cancer, thereby promoting the disease to further spread to other organs. By inhibiting these proteins, immune checkpoint blockers allow the immune system to work properly and destroy cancer cells at a faster pace.
The second phase of the study, which was conducted by Arnaud Scherpereel, MD, PhD, a thoracic oncologist at the University Hospital of Lille in France, included 125 pleural mesothelioma patients who were experiencing relapse. Most of participants – 80% – were male and their median age was 72. The following findings focus only on 108 of the patients, as this is the data available at present. 63 individuals were administered nivolumab alone, while the remaining 62 received a combination of nivolumab and ipilimumab. A disease control rate of 42.6% was achieved in people who received nivolumab, whereas a 51.9% disease control rate was noted in those who were treated with both nivolumab and ipilimumab. “This randomized phase 2 trial may be enough to support the use of immune checkpoint inhibitors in this setting, but it is too early to conclude whether nivolumab alone or the combination of nivolumab and ipilimumab is better,” Dr. Scherpereel said. 70% of mesothelioma patients were administered 3 cycles of treatment, regardless of the drug/s it involved.
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While a reduction in the size of the tumor was noted in 17% of individuals who received nivolumab, the tumors of 26% of people treated with nivolumab and ipilimumab shrank. As for progression-free survival, 4 months was the time for the former group, whereas for the latter, their mesothelioma stagnated for 5.6 months. When it came to side effects, participants who were given the both drugs were more susceptible to facing unpleasant symptoms, including grade 3 or 4 toxicities. Some of the adverse effects of the treatment were:
- colon inflammation
- thyroid problems
- skin rashes
It is worthy of note that, during the second phase of the study, 3 deaths were registered among the group who received the combination of drugs, which occurred due to acute renal failure, metabolic encephalopathy, and fulminant hepatitis. Nevertheless, only the latter was associated with the treatment itself. “Mesothelioma cells build a protective tumor microenvironment to shield themselves against the immune system's attacks and even act against anti-tumor immune response. Therefore, therapies that shift the tumor microenvironment from a state of immune suppression to one of immune activation may hold promise in MPM,” said Dr. Scherpereel.