Modeling Tumor Size Time Course In Platinum Resistant/Refractory Ovarian Cancer Patients Treated With Vanucizumab.

e17042 Background: Vanucizumab is a novel bi-specific IgG-like antibody which is directed against both VEGF-A and ANG2, two key factors in tumor angiogenesis. As such, vanucizumab represents an encouraging approach in preventing tumor growth in a variety of cancer types Methods: Eligible patients (pts) with platinum (Pt)-resistant/ refractory epithelial OC (PROC) were treated with vanucizumab at 30 mg/kg IV Q2W until disease progression or unacceptable toxicity. Patients underwent tumor assessment by CT scan at screening, and then every 8 weeks while on study. According to RECIST 1.1, target lesions (max 5 and max 2 per organ, representative of key organs) were summed to yield summary of the longest lesion diameter (SLD). Longitudinal modeling of such SLD data allows quantification of the effect of anticancer therapies in addition to the RECIST criteria. Overall, the SLD data set contained 143 observations (SLD measurements per patient: mean 3.6, range 2-6), and pts received on average 9 cycles of treatment. Longitudinal SLD data were analyzed by means of a population mixed-effect model to quantitatively estimate metrics of efficacy, such as maximum shrinkage and time to tumor regrowth after treatment onset, together with critical kinetic parameters such as the natural growth rate of the tumor Results: Objective response as per RECIST was demonstrated in 8/41 (20%) and 8/28 (29%) for all and bevacizumab naïve pts, respectively. The maximum tumor shrinkage from baseline was calculated to be 49% (95% CI: 47-52%), with a time to re-growth of 5.5 months (95% CI: 5.2-5.7 months). The unperturbed tumor growth rate was estimated to be roughly 0.7 mm/week, suggesting that a tumor of 100 mm in size would gain approximately 5.6 mm after 8 weeks if left untreated. After 8 weeks of vanucizumab treatment, its size would be decreased by approximately 32 mm Conclusions: Longitudinal modelling of SLD data is a useful technique allowing extraction of key metrics of tumor shrinkage over time and comparison of effect between different treatments. Vanucizumab 30 mg/kg Q2W was shown to be clinically active in pts with PROC, and thus may represent a novel therapy, either alone or in combination with immunotherapy or chemotherapy. Clinical trial information: NCT01688206.