Mesothelioma Clinical Trial Matches Treatment to Genetic Profiles

Scientists at the University of Leicester in the United Kingdom recently published phase 2 clinical trial results involving abemaciclib, a new genetic therapy for malignant pleural mesothelioma.

Researchers designed the trial to match mesothelioma treatment to a patient’s specific genetic profile. The early study results are promising for mesothelioma patients who have previously received first-line chemotherapy with pemetrexed and either cisplatin or carboplatin.

Restoring Gene Function Promotes Tumor Destruction

Abemaciclib, available under the brand names Verzenio and Ramiven, is approved by the U.S. Food and Drug Administration for breast cancer patients with specific genetic biomarkers. The drug blocks the CDK4 and CDK6 enzymes, which inhibit tumor cells from reaching apoptosis, a form of cell death.

Researchers leading the mesothelioma clinical trial, termed MiST2, believe that finding the proper treatment for each person is key to developing a cure.

They noted that mesothelioma tumors without the chromosome locus 9p21.3, which is responsible for expressing a protein called CDKN2A-MAP, led to shorter overall survival in patients. The researchers used abemaciclib to restore the associated tumor suppressor, p16ink4A, and improve mesothelioma survival.

Study Results Promising for Mesothelioma Patients

The MiST2 study enrolled 26 mesothelioma patients between 2019 and 2020. Each patient tested negative for the tumor suppressor gene, indicating they might benefit from abemaciclib.

Study authors administered abemaciclib as second-line therapy. All the patients in the study had previous treatment with mesothelioma chemotherapy, including pemetrexed (Alimta) and either cisplatin or carboplatin.

Trial participants received 200 mg of abemaciclib twice daily over 12 weeks while researchers monitored patients for drug safety and effectiveness.

The study found that abemaciclib achieved disease control in 54% of mesothelioma patients after 12 weeks. Three patients had a partial response to the gene therapy, and 11 patients had stable disease after the same timeframe.

At the study’s primary endpoint, the median progression-free survival had reached over 18 weeks with a median overall survival of 31 weeks.

Side Effects Common, Predominantly Mild

The most common side effects in the study were diarrhea and fatigue, affecting 92% of study participants.

Only three of the 26 patients in the study, 12%, experienced treatment-related adverse events that study authors classified as Grade 3. These side effects included diarrhea, shortness of breath, low blood platelets, vomiting and pulmonary embolism.

About 23% of participants experienced severe adverse events causing one patient to discontinue treatment. One patient had an extreme adverse event related to diarrhea, and a single patient died due to neutropenic sepsis.

Promising Results Lead to Further Study

Study authors summarized the current data by noting that the trial has helped scientists understand how mesothelioma patients respond to gene therapy.

“This study met its primary endpoint, showing promising clinical activity of abemaciclib in patients with p16ink4A-negative mesothelioma who were previously treated with chemotherapy,” the authors concluded. “[This therapy] warrants further investigation in a randomized study as targeted stratified therapy.”

Some patients may have genes that allow a particular response to a drug, such as abemaciclib, but there is still potential to find targets beneficial to other patients.

The researchers are interested in adding additional therapy options for patients as the clinical trial continues. Depending on their genetic profile, patients may also receive rucaparib, an FDA-approved drug for certain types of ovarian cancer, or a combination of immunotherapy drugs.

Contingent on the trial’s success in the future, it may expand to more mesothelioma cancer treatment centers across the U.K. Identifying additional biomarkers that can treat a broader range of patients is key to developing treatment plans tailored to each patient’s disease.

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