Cediranib for Mesothelioma: VEGF Inhibitor Fails Another Trial

Cediranib for mesothelioma appears to be ruled out by another failed clinical trial. 

A new study led by MD Anderson researchers concludes that the VEGF inhibitor causes too many side effects for not enough survival benefit. 

It is a blow to researchers hoping to use cediranib for mesothelioma patients on chemotherapy. 

Cutting Off Tumor Blood Supply

Cediranib is an oral drug made by AstraZeneca. It is part of a class of drugs called VEGF inhibitors. Vascular endothelial growth factor (VEGF) is a signal protein that stimulates blood vessel formation in tumors. Research shows that mesothelioma patients who have higher serum levels of VEGF have a lower chance of survival. 

VEGF inhibitors like cediranib latch onto VEGF receptors inside mesothelioma cells. This blocks cells from receiving VEGF signals. The theory is that cediranib for mesothelioma could keep tumors from growing and spreading. 

Standard mesothelioma chemotherapy is only moderately effective. MD Anderson researchers hoped that giving cediranib along with chemotherapy would enhance the effect and help patients live longer. A Phase I study of the combination looked promising.

Chemotherapy + Cediranib for Mesothelioma

There were 92 mesothelioma patients in the Phase II study. Three out of the four of them had the epithelioid mesothelioma subtype. The rest had sarcomatoid or biphasic mesothelioma.

The patients in the study were not eligible for mesothelioma surgery. Instead, they all got standard chemotherapy with cisplatin and Alimta. 

Half of the patients also got a placebo and the other half took oral cediranib for mesothelioma along with chemotherapy.

“The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss,” reports lead researcher Anne Tsao, MD. 

Among the patients that received cediranib for mesothelioma, it took about two months longer for their cancer to start growing again. But they did not live any longer than the placebo group. 

The research team concludes that the downsides of using cediranib for mesothelioma outweigh the upsides. 

“The cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM,” they write.

Other Trials Produced Similar Results

Several previous trials of cediranib for mesothelioma have also been disappointing. 

A 2012 University of Chicago study tested cediranib as a stand-alone mesothelioma treatment. The study showed that the drug did have an effect on mesothelioma tumors when the dose was high enough. But patients who took the higher dose also got much sicker.

That study included 51 mesothelioma patients enrolled at nine different centers. It found that cediranib for mesothelioma caused blood clots in the lungs, confusion, seizures, and vision loss.

Studies of cediranib for other cancers suggest that it does not usually work well by itself. Current studies are focused on cediranib’s potential to boost other cancer treatments. 

Sources:

Tsao, A, et al, “Phase II Trial of Cediranib in Combination With Cisplatin and Pemetrexed in Chemotherapy-Naïve Patients With Unresectable Malignant Pleural Mesothelioma (SWOG S0905)”, August 6, 2019, Journal of Clinical Oncology, https://ascopubs.org/doi/abs/10.1200/JCO.19.00269