From the blog

A Gene Therapy Could Improve Survival for Mesothelioma

Published: March 4, 2022

Results from a new study involving a genetic therapy for pleural mesothelioma have been submitted at the University of Leicester. Researchers at the United Kingdom university designed a treatment to match specific genetic profiles to individual patients. There are promising results from the study, which had patients who received first line chemotherapy combined with either cisplatin or carboplatin prior to this study.

The drug being tested is abemaciclib (brand names are Verzenio and Ramiven). It is approved by the Food and Drug Administration for breast cancer patients with specific biomarkers. The drug blocks CDK4 and CDK6 enzymes, which inhibit tumor cell apoptosis, or cell death. The trial known as MiSt2 has found that individualizing each treatment for patients with cancer is the best way to find a cure. The researchers found that patients who had tumors without the chromosome locus 9p21.3, which expresses a protein called CDKN2A-MAP, had a shorter survival. The researchers gave patients abemaciclib, which restored the needed tumor suppressors p16ink4A. This created a better survival in mesothelioma patients.

There were 26 mesothelioma patients from 2019 to 2020 in the MiST2 study. All patients tested negative for the tumor suppressor gene, making them prime candidates for abemaciclib. Abemaciclib was given to patients as a second line treatment. The patients previously had first line treatments of pemetrexed and cisplatin or carboplatin. They received 200 mg of abemaciclib twice a day for more than 12 weeks while the researchers monitored the patients for safety and effectiveness. There was disease control in 54 percent of mesothelioma patients after 12 weeks. There were three patients with a partial response to the gene therapy and 11 patients had stable disease. Patients in the study had a progression free survival of 18 weeks with a median overall survival of 31 weeks.

Most study participants had side effects, but they were considered mild. Ninety-two of the patients had diarrhea and fatigue. Twelve percent, or three of the 26 patients, had Grade three treatment related adverse events including diarrhea, shortness of breath, low blood platelets, vomiting, and pulmonary embolism. Around 23 percent of the participants had severe adverse events, with one having to end the study. One patent had a severe adverse event relating to diarrhea and one patient died from neutropenic sepsis.

This research has helped scientists learn how gene therapy affects mesothelioma patients. The researchers believe that the topic should be researched further as a targeted stratified therapy. Some patients may respond to abemaciclib, but there are other genes that patients with mesothelioma could have that could be targeted. The scientists are now looking into other treatments that could be used alongside the drug regimen. They want to use rucaparib for people with certain gene profiles. It is an approved drug for treating ovarian cancer. They also want to use some types of immunotherapy drugs. The gene treatment could go to more treatment centers in the U.K if it is found to be successful. Researchers need to find other biomarkers so more patients can benefit from treatments like this. If more are found, more patients with hard-to-treat cancers could live much longer.

Dean A. Fennell et al., “Abemaciclib in patients with p16ink4A-deficient mesothelioma (MiST2): a single-arm, open-label, phase 2 trial” The Lancet Oncology (March 2022. [Link]
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