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Ramucirumab and Gemcitabine are Showing Promising Results as a Second Line Treatment for Pleural Mesothelioma

Published: September 17, 2021

Combining the drug ramucirumab with the chemotherapy drug gemcitabine is showing to be a successful second line treatment for pleural mesothelioma. Ramucirumab is a type of immunotherapy drug called a monoclonal antibody, which targets and restricts proteins that stimulate blood vessel growth in tumors. The Lancet Oncology published the results of the Italian study involving 26 hospitals around the country. The study had impressive results, which could lead to the drug combination being used as a second line treatment for mesothelioma.

The study was randomized, double-blind, and placebo controlled and all patients received prior first line treatment. Eighty of the patients received the ramucirumab and gemcitabine combination while 81 received gemcitabine and a placebo. All patients in the study had disease progression after their first line treatment of pemetrexed and cisplatin. The ramucirumab group had a median overall survival of 13.8 months versus 7.5 months for the placebo group. The six-month survival was improved to 76 percent for ramucirumab compared to the placebo group being 56.5 percent. The 12-month survival was also greatly improved for the study group with a 63.9 percent survival compared to the 33.9 percent survival for the placebo. The patients saw a median progression free survival of 6.4 months, which was longer than the 3.3 months for the placebo group. The disease control rate was 73 percent for the ramucirumab group versus 52 percent for the placebo group. Finally, the duration of the response to treatment was improved to 8.4 months compared with 5.4 months for the placebo group. Improvement was seen in the ramucirumab group regardless of the histological subtype of the disease and the time to progression of the first line treatment.

Ramucirumab has been approved as a second line treatment for other cancers including colorectal cancer, non-small cell lung cancer, gastric adenocarcinoma, and hepatocellular carcinoma. Pleural mesothelioma patients are usually given gemcitabine as a second line treatment to extend survival, but it is usually not effective for patients when used alone. The study showed that ramucirumab is a safe drug since serious side effects were only seen in six percent receiving the treatment and five percent receiving the placebo. Grade three or four adverse events (less serious) were also seen in patients with the most common one being neutropenia, also known as low white blood cell count, in 20 percent of patients receiving ramucirumab and 12 percent receiving the placebo.

Ramucirumab is also showing effectiveness when combined with Opdivo (nivolumab) as a second line treatment. Nivolumab and ipilumab were recently approved as a treatment by the Food and Drug Administration for the use in mesothelioma, and some patients now take it as a first line treatment instead of chemotherapy. Many oncologists believe immunotherapy will be an important step in treating mesothelioma, and ramucirumab and chemotherapy could become the new standard second line treatment for mesothelioma.

Carmine Pinto et al., “Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial” The Lancet Oncology (September 6, 2021). [Link]
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