Role of 3-D volume growth rate for drug activity evaluation in meningioma clinical trials: the example of the CEVOREM study.

Background We aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome. Methods We performed a posthoc analysis based on volume data and 3DVGR extracted from CEVOREM study including 18 patients with 32 recurrent high-grade meningiomas and treated with everolimus and octreotide. The joint latent class model was used to classify tumor 3DVGR under treatment. Results Class 1 includes lesions responding to treatment with decrease in volume in the first 3 months, and then a stabilization thereafter (9.5% of tumors) (mean pretreatment 3DVGR=6.13%/month; mean under treatment 3DVGR=-18.7%/month within 3 first months and -0.14%/month after the 3 first months). Class 2 includes lesions considered as stable or with a slight increase in volume under treatment (65.5%) (mean pretreatment 3DVGR=6.09%/month; under treatment 3DVGR=-0.09% within the first 3 months). Class 3 includes lesions without 3DVGR decrease (25%) (mean pretreatment 3DVGR=46.9%/month; mean under treatment 3DVGR=19.2%/month within the first 3 months).Patients with class 3 lesions had a significantly worse progression free survival rate (PFS) than class 1 and 2 ones. Discussion Tumor 3DVGR could be helpful to detect early signal of drugs antitumoral activity or non-activity. This volume response classification could help in the assessment of drug activity in tumors with mostly volume stabilization and rare response as aggressive meningiomas even with a low number of patients in complement to 6 months PFS.