A phase 2 clinical trial testing anetumab ravtansine against the chemotherapy drug vinorelbine did not provide the results investigators hoped for mesothelioma.
Anetumab ravtansine, a type of immunotherapy, did not improve overall survival or progression-free survival compared to vinorelbine. The study was led by Dr. Hedy Lee Kindler of University of Chicago Medicine. She is the Mesothelioma Program Director at the University of Chicago Comprehensive Cancer Center.
The trial was specifically for cases of relapsed pleural mesothelioma, meaning cancer that had responded to treatment but started spreading again. Mesothelioma relapse or recurrence is quite common, and patients usually survive for just a few months once recurrence occurs.
Anetumab Ravtansine: What Is the Therapy?
Anetumab ravtansine is a mesothelioma monoclonal antibody, which is a class of immunotherapy treatment for cancer. It is a chemically engineered treatment to help the immune system. Monoclonal antibodies are still in testing for mesothelioma and most other cancers.
Anetumab ravtansine is a mesothelin-targeter. Mesothelin, a protein, is often seen on the surface of mesothelioma cells. Anetumab ravtansine binds to mesothelin and prevents cancer cells from dividing and growing. This inhibits tumor growth and slows the cancer’s development.
Healthy cells have a lifecycle ending with apoptosis, which is called “cell death.” Cells replicate before dying to keep the body healthy. Cancer cells often avoid apoptosis – replicating without dying, which leads to a biological imbalance as cells overpopulate an area and bunch together, forming tumors.
Anetumab ravtansine enters the diseased cells via binding with mesothelin and causes the release of a cytotoxic agent, DM4. Cytotoxic agents kill healthy and diseased cells, so DM4 forces mesothelioma cells expressing mesothelin to commit cell death.
No Improvement in Survival With Anetumab Ravtansine
The trial had 248 participants split into two groups: one receiving the monoclonal antibody and the other receiving vinorelbine chemotherapy. The vinorelbine group received 30 mg/m² once every week and the anetumab ravtansine group received 6.5 mg/kg² once every three weeks.
The median progression-free survival was 4.3 months for anetumab ravtansine and 4.5 months for vinorelbine. Around 32% of anetumab ravtansine patients survived for 8 months, while 41% of vinorelbine patients reached this mark. The median overall survival was 9.5 months for anetumab ravtansine and 11.6 months for vinorelbine.
Mesothelioma Guide previously reported vinorelbine is a viable option for relapsed mesothelioma. Based on multiple studies, the overall survival for most patients is 4-5 months after relapse occurs. Vinorelbine is not approved by the U.S. Food and Drug Administration for mesothelioma.
Better Safety Tolerability Than Chemotherapy
The main positive takeaway from the phase 2 study was the safety and quality of life for patients. Mild or severe adverse events/side effects from treatment occurred in under half (48%) of the anetumab ravtansine group, compared to 74% for vinorelbine.
Difficult breathing was the most common side effect from anetumab ravtansine. Neutropenia occurred in nearly half of the vinorelbine patients.
Grade 3 pneumonia occurred in only 4% of the monoclonal antibody patients, compared to 7% for vinorelbine.
Sources & Author
- Anetumab Ravtansine vs Vinorelbine in Relapsed Mesothelin-Positive Advanced Malignant Pleural Mesothelioma. American Society of Clinical Oncology. Retrieved from: https://ascopost.com/news/april-2022/anetumab-ravtansine-vs-vinorelbine-in-relapsed-mesothelin-positive-advanced-malignant-pleural-mesothelioma/. Accessed: 04/08/2022.
Sources & Author