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Second-Line Treatment with Ramucirumab Improves Mesothelioma Survival

second-line treatment with ramucirumabNew evidence suggests that second-line treatment with ramucirumab after first-line chemotherapy may lead to longer survival in people with pleural mesothelioma. 

Researchers in Italy recently published results of a double-blind, placebo-controlled trial of the drug. Ramucirumab inhibits a protein mesothelioma tumors need to form new blood vessels. 

The study included 161 pleural mesothelioma patients from across Italy. Researchers gave half of them second-line treatment with ramucirumab and another drug called gemcitabine. The other half had second-line treatment with gemcitabine alone. 

Results showed the ramucirumab group lived more than six months longer than those who got only gemcitabine. 

Few Options for Recurrent Mesothelioma

Pleural mesothelioma is an aggressive cancer with few good treatment options. Most patients start with chemotherapy with Alimta. Some go on to have surgery. A few have radiation, too. Last year, the FDA also approved an immunotherapy protocol that helps some people.

There are no standards for what to do if mesothelioma recurs after first-line treatment. Some studies suggest that second-line chemotherapy with Alimta might help patients who responded well the first time around. 

But what about patients who fail to respond to Alimta? The Italian study suggests that second-line treatment with ramucirumab could be an option for these patients. 

Ramucirumab is a VEGFR-2 blocker. This protein plays a critical role in forming the blood vessels mesothelioma tumors need to grow and spread. Cutting off a tumor’s blood supply may also make it more vulnerable to treatment with another drug. 

Testing Second-Line Treatment with Ramucirumab

The RAMES study focused on mesothelioma patients whose cancer kept growing during or after standard chemotherapy. It ran from 2016 to 2018. One-hundred and sixty-one patients received 1000 mg of intravenous gemcitabine on days 1 and 8 every 3 weeks.

Eighty patients received second-line treatment with ramucirumab along with the gemcitabine. The other 81 had gemcitabine plus placebo. 

“At database lock (March 8, 2020), with a median follow-up of 21·9 months,, overall survival was longer in the ramucirumab group,” reports lead author Carmine Pinto, MD. “Median overall survival was 13·8 months in the gemcitabine plus ramucirumab group and 7·5 months in the gemcitabine plus placebo group.”

The downside is that 44 percent of patients on second-line treatment with ramucirumab had negative side effects. Only 30 percent of mesothelioma patients in the placebo group had comparable side effects. The rate of life-threatening complications was only slightly higher in the ramucirumab group. There were no treatment-related deaths. 

Dr. Pinto concludes, “Ramucirumab plus gemcitabine significantly improved overall survival after first-line standard chemotherapy, with a favourable safety profile.”

Second-line treatment with ramucirumab and gemcitabine could be a new option for pleural mesothelioma patients whose cancer comes back after standard treatment. 


Pinto, C, 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”, September 6, 2021, The Lancet Oncology, https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00404-6/fulltext


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