Response Assessment of 68Ga-DOTA-E-[c(RGDfK)]2 PET/CT in Lung Adenocarcinoma Patients Treated with Nintedanib Plus Docetaxel

Abstract

Nintedanib is an oral angiokinase inhibitor used as second-line treatment for non-small cell lung cancer. New radiotracers, such as ⁶⁸Ga-DOTA-E-[c(RGDfK)]², that target α_vβ₃ integrin might have an impact as a noninvasive method for assessing angiogenesis inhibitors. Methods: From July 2011 through October 2015, 38 patients received second-line nintedanib plus docetaxel. All patients underwent PET/CT with ⁶⁸Ga-DOTA-E-[c(RGDfK)]² radiotracer and blood-sample tests to quantify angiogenesis factors (fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor AB) before and after completing 2 therapy cycles. Results: Of the 38 patients, 31 had available baseline and follow-up PET/CT. Baseline lung tumor volume addressed with ⁶⁸Ga-DOTA-E-[c(RGDfK)]² PET/CT correlated with serum vascular endothelial growth factor levels, whereas baseline lung/liver SUV_max index correlated with platelet-derived growth factor AB. After treatment, the overall response rate and disease control rate were 7.9% and 47.3%, respectively. A greater decrease in lung tumor volume (-37.2% vs. -27.6%) was associated with a better disease control rate in patients (P = 0.005). Median progression-free survival was 3.7 mo. Nonsmokers and patients with a higher baseline lung tumor volume were more likely to have a higher progression-free survival (6.4 vs. 3.74 [P = 0.023] and 6.4 vs. 2.1 [P = 0.003], respectively). Overall survival was not reached. Patients with a greater decrease in lung SUV_max (not reached vs. 7.1 mo; P = 0.016) and a greater decrease in the lung/spleen SUV_max index (not reached vs. 7.1; P = 0.043) were more likely to have a longer overall survival. Conclusion:⁶⁸Ga-DOTA-E-[c(RGDfK)]² PET/CT is a potentially useful tool for assessing responses to angiogenesis inhibitors. Further analysis and novel studies are warranted to identify patients who might benefit from this therapy.

Keywords: 68Ga-DOTA-E-[c(RGDfK)]2; adenocarcinoma; angiogenesis; nintedanib/docetaxel; αvβ3 integrin.