Mesothelioma Community Optimistic About Lung Cancer Clinical Trial

In November, Mesothelioma Help reported on the “unprecedented response rates” in lung cancer patients in a Phase II clinical trial. In early results of the study with patients who were given poziotinib, an investigational oncology drug, all of the patients experienced some tumor shrinkage. Now, the researchers report they are expanding the clinical trial and the mesothelioma community is taking notice.

Lung cancer and mesothelioma patients with the epidermal growth factor receptor (EGFR) biomarker have been the focus of targeted treatment. However, the effectiveness of the mesothelioma treatments have not been as successful as researchers had hoped. After looking closer at the EGFR markers, it is those cancers with an additional mutation, exon 20, that resisted the EGFR inhibitors. When poziotinib was used against that specific alteration, the drug hit a “bulls-eye,” according to an April 23 press release from the researchers of the Moon Shots program at MD Anderson Cancer Center.

Researchers are “encouraged” by results of the 11 patients in the clinical trial with seven of them, or 64%, having confirmed tumor shrinkage. The team now hopes to offer this treatment to 80 patients through the clinical trial, and reports that 47 are now enrolled with EGFR. 12 patients are enrolled in the human epidermal growth factor receptor 2 (HER2) arm of the trial.

“We need to see if these unprecedented response rates are maintained through the remainder of the trial, but our scientific findings provide a basis for optimism,” says John Heymach, M.D., professor and chair of Thoracic/Head and Neck Medical Oncology.

The EGFR gene is overexpressed in more than 50% of pleural mesothelioma patients, and in approximately 15% of lung cancer patients. According to the MD Anderson researchers, of those, just three percent express the exon 20 mutation. Primary treatment for the EGFR mutation is afatatinib. In initial research, the team found that  poziotinib -treated mice had their tumor burden reduced by half, while those treated with afatinib had no reduction.

Approximately 2,500 to 3,000 Americans are diagnosed with mesothelioma, an asbestos-caused cancer, each year. The most common form of the cancer is malignant pleural mesothelioma, affecting the lining of the lungs. The cancer resists standard treatments and can build up a resistance to the powerful chemotherapy drugs used to attack the aggressive cancer. Personalized treatment targeted to the unique characteristics of the patient, such as the exon 20 insertion, optimizes the potential for success.

“These data identify poziotinib as a potent, clinically active inhibitor of EGFR and HER2 exon 20 mutations,” the team concluded. They will continue with the lung cancer research in addition to investigating the drug’s effectiveness in other cancers with the exon 20 insertion.

Read the latest update on the study in the April 23 issue of Nature Medicine.
https://www.nature.com/articles/s41591-018-0007-9

To find out more about the Clinical trial, see ClinicalTrials.gov.
https://clinicaltrials.gov/ct2/show/record/NCT03066206

Sources:

• Moon Shots program at MD Anderson Cancer Center
  https://www.mdanderson.org/newsroom/2018/04/size-structure-help-poziotinib-pose-threat-to-deadly-exon-20-lung-cancer.html