When Chemotherapy Fails: Apatinib May Offer Third-Line Option for Mesothelioma Patients

An investigational drug being developed in China may offer a third lifeline to mesothelioma patients whose cancer does not respond to other chemotherapy drugs.

Apatinib, also called YN968D1, is a tyrosine kinase inhibitor that is thought to help prevent the formation of blood vessels that mesothelioma tumors need to grow and spread.

Right now, there is no approved second-line treatment for pleural mesothelioma, let alone a third-line treatment. Chinese researchers at 363 Hospital in Cheng Du — along with mesothelioma patients around the world — are hoping that apatinib will change that.

Mesothelioma Case Study

The researchers are hanging their hopes on the case of a 58-year old woman who showed up at their hospital complaining that she had had chest tightness and shortness of breath for three months.

Although chest tightness and breathlessness are common symptoms of mesothelioma, they are also common signs of many other respiratory conditions. Because mesothelioma is so rare, it is not usually one of the first illnesses for which doctors check.

However, when the Chinese patient underwent a PET/CT scan, her doctors could see some of the tell-tale signs of pleural mesothelioma — a tumor involving both layers of the pleural lining around the lungs as well as enlarged pulmonary lymph nodes.

An examination of cells from the patient’s excess lung fluid (another common mesothelioma symptom) confirmed that she had advanced epithelioid mesothelioma.

Escalating Mesothelioma Treatments

Like most mesothelioma patients, the woman in the case study was first treated with a combination of pemetrexed (Alimta) and cisplatin. Since 2004, Alimta has remained the only drug approved by the FDA for the treatment of mesothelioma.

When the patient’s mesothelioma tumor stopped responding to that combination, her doctors upped their game with a combination of gemcitabine (Gemzar) and cisplatin. This combination is one of the most thoroughly tested possibilities for second-line mesothelioma treatment.

But within just a few months, both combinations stopped working, so the woman’s doctors decided to try apatinib. At first, the patient was given 250 mg/day of apatinib. After a week, the dose was bumped up to 500 mg/day.

While apatinib was not a cure for mesothelioma, it was surprisingly effective at holding the cancer at bay after other chemotherapy drugs failed to do so.

“A 5-month progression-free survival was achieved,” the team reports in the Baltimore medical journal Medicine. “Apatinib may be a potential therapeutic drug for malignant pleural mesothelioma, particularly as a third-line treatment in cases resistant to chemotherapeutic options.”

Mesothelioma’s notorious resistance to standard chemotherapy is one of the reasons it is considered so deadly. While it can take decades after asbestos exposure for mesothelioma symptoms to show up, once they do, the disease tends to spread quickly. Many mesothelioma patients succumb to the disease within six to eight months of diagnosis.

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines support second-line chemotherapy while acknowledging that data on the practice is limited.The European Society of Medical Oncology and the Third Italian Consensus Conference for MPM both recommend that relapsed mesothelioma patients consider enrolling in clinical trials.

Source:

Du, S, et al, “Apatinib for salvage treatment of advanced malignant pleural mesothelioma: A case report”, November 2018, Medicine (Baltimore), https://journals.lww.com/md-journal/Fulltext/2018/11090/Apatinib_for_salvage_treatment_of_advanced.46.aspx