Research and clinical trials
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Researchers have made significant advances in mesothelioma treatment advances recently, including promising work with immunotherapy.
The first FDA-approved combination immunotherapy for mesothelioma, nivolumab and ipilimumab, known by the brand names Opdivo and Yervoy, has been effective for many patients.
In September 2021, the European Society of Medical Oncology presented study data showing a three-year survival rate of 23% for mesothelioma patients in Opdivo and Yervoy. By comparison, the three-year survival rate for chemotherapy patients was 15%.
However, some patients cannot receive immunotherapy drugs due to chronic medical conditions or a lack of specific biomarkers. Also, immunotherapy is not a definitive solution to mesothelioma. For example, Opdivo and Yervoy are only available as a first-line treatment for mesothelioma patients, not if the cancer has returned after previous treatment.
In many cases, current immunotherapy can improve survival compared to conventional methods, but there is still room for improvement. The most effective treatments for mesothelioma include a multimodal approach that combines immunotherapy with surgery, chemotherapy, radiation, or other procedures.
5 Promising Advances in Immunotherapy for Mesothelioma
In November, Dr Anna Novak, a researcher at the Institute of Respiratory Health in Perth, Western Australia, published her team’s report on updates on the latest trials of immunotherapy for mesothelioma.
Nowak’s focus is on treatment with an immune checkpoint inhibitor, the same class of drugs as Opdivo and Yervoy. Also known as checkpoint treatments, these therapies have great potential to improve pleural mesothelioma prognosis and life expectancy.
“The most impressive advance in checkpoint blockade has been to demonstrate that for people with sarcomatoid and biphasic mesothelioma, we can double survival with a combination of ipilimumab and nivolumab,” Nowak told Asbestos.com’s Mesothelioma Center.
This recent study provided an overview of recent clinical trials for malignant mesothelioma of the pleura and highlighted promising new advances in immunotherapy.
- Second line nivolumab: The CONFIRM randomized study collected 332 participants who had failed one or two previous lines of treatment. Both pleural and peritoneal mesothelioma were eligible. Second-line nivolumab alone improved overall survival from 6.9 months to 10.2 months compared to the placebo group. The median progression-free survival was three months.
- Anti-CTL4 and Anti-PD-L1 combinations: The NIBITMeso phase II trial tested the anti-CTLA4 agent tremelimumab with the anti-PD-L1 agent durvalumab (Imfinzi) as first-line or second-line therapy. Among the 40 participants, 65% of patients had disease control. The INITIATE study tested first-line nivolumab and ipilimumab in 38 patients, with 68% demonstrating disease control.
- Chemotherapy with Checkpoint Blockade: Results from the PrE0505 study support the possibility of combining chemotherapy with checkpoint inhibitors or inhibitors. This 55-patient study combined the chemotherapy drugs cisplatin and pemetrexed with durvalumab. The median overall survival was 20.4 months, and the median progression-free survival was 6.7 months.
- Vital Signs Test for Checkpoint Blockade: Recent evidence suggests that assaying the expression of PD-L1 biomarkers is not a good indicator of the success of anti-PD-L1 immunotherapies such as pembrolizumab (Keytruda). However, new studies show that monitoring PD-L1 using radioactive tracers provides a practical, real-time level of biomarker activity.
- Correct sequence of immunotherapies: There are limited data on immunotherapy patients receiving treatment before or after other treatments. However, the CheckMate 743 trial indicated that the use of new adjuvants could effectively reduce tumor size before surgery for mesothelioma treatment. Several pilot clinical trials are examining both adjuvant and induced checkpoint barriers.
Some types of mesothelioma cells, such as the epithelium, respond less well to immunotherapy. Nowak believes that more research will reveal new options for these patients.
“That’s why we need to support clinical trials that will answer that question,” she said. “I am optimistic that the combination of chemotherapy and barrier blockade may be as useful in treating epithelial mesothelioma as it has double checkpoint blockade for non-epithelial mesothelioma.”
Antiangiogenics are becoming the new standard for immunotherapy
Scientists continue to study new drugs and treatments for mesothelioma that improve overall survival and safety for more people. A 2021 study recently published in the Journal of Cancer Mesothelioma and Treatment evaluated several ways in which mesothelioma immunotherapy is developing.
In addition to Opdivo and Yervoy for treating non-resectable malignant mesothelioma, scientists are looking for other combinations of immunotherapy. One method that has proven effective is antiangiogenic, which is a type of immunotherapy that targets blood vessels.
Angiogenesis is the process of creating new blood vessels. In cancer, tumors form blood vessels to use oxygen to grow and spread. Antiangiogenic drugs inhibit vascular endothelial growth factors, or VEGF. These drugs prevent the growth of new blood vessels, effectively starving tumors of oxygen and nutrients.
The popular VEGF inhibitor of mesothelioma, bevacizumab, was recently part of a large phase III randomized controlled trial conducted by the French Collaborative Group for Treatment of Chest Tumors (IFCT). This study recruited patients with non-resectable pleural mesothelioma who had not received prior chemotherapy.
The primary endpoint was significantly longer median overall survival with bevacizumab added to chemotherapy at 18.8 months versus 16.1 months with chemotherapy alone. However, adverse events such as hypertension and bleeding were more common in the bevacizumab group.
Recently, studies such as the phase II RAMSES trial in 2020 showed promising results of combining anti-VEGF drugs with chemotherapy as a second line therapy. The addition of the VEGF inhibitor ramucirumab significantly improved median overall survival to 13.8 months compared to 7.5 months for chemotherapy alone.
Future clinical trials will undoubtedly depend on the success of current immunotherapies, including VEGF inhibitors, checkpoints, and more. In 2022, researchers will find ways to improve the efficacy, response rate, and safety of these treatments for mesothelioma patients.
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