Changes in 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine Positron Emission Tomography Imaging in Patients with Non–Small Cell Lung Cancer Treated with Erlotinib

Abstract

Purpose: Assessing clinical activity of molecularly targeted anticancer agents, especially in the absence of tumor shrinkage, is challenging. To evaluate on-treatment 18F-fluorodeoxyglucose (FDG) and/or 18F-fluorodeoxythymidine (FLT) positron emission tomography (PET) for this purpose, we conducted a prospective multicenter trial assessing PET response rates and associations with progression-free (PFS) and overall survival (OS) in 2nd/3rd-line non-small-cell lung cancer patients treated with erlotinib.Experimental Design: PET/computed tomography (CT) scans were conducted at baseline, day (d)14 and d56 after the first daily erlotinib dose, with diagnostic CT at baseline and d56 (all scans centrally reviewed). PET partial metabolic response (PMR) was defined as a mean decrease (in 5 lesions/patient) of 15% or more maximum standardized uptake value. PFS was investigator-determined.Results: Of 74 erlotinib-treated patients, 51 completed all imaging assessments through d56; 13 of 51 (26%) FDG-evaluable patients had PMR at d14, as did 9 of 50 (18%) FLT-evaluable patients. Four (7.8%) showed partial responses (PR) by d56 CT; all 4 had PMR by d14 FDG-PET with 3 PMRs by d14 FLT-PET. Three of the 4 patients with CT PR had evaluable archival tumor tissue; all 3 had epidermal growth factor receptor mutations. D14 and d56 PMRs by FDG or FLT were associated with improved PFS; HRs for PET responders versus nonresponders were 0.3 to 0.4. D14 FDG-PET PMR was associated with improved OS (P ¼ 0.03) compared with FDG-PET nonresponders.Conclusion: Early (d14) FDG-PET PMR is associated with improved PFS and OS, even in the absence of subsequent Response Evaluation Criteria in Solid Tumors response. These data support inclusion of FDG-PET imaging in clinical trials testing novel targeted therapies, particularly those with anticipated cytostatic effects. Clin Cancer Res; 17(10); 3304-15. Ó2011 AACR.

Quantitative Analysis of Response to Treatment with Erlotinib in Advanced Non–Small Cell Lung Cancer Using 18F-FDG and 3′-Deoxy-3′-18F-Fluorothymidine PET

“…Therefore, a proportion of patients who benefit from erlotinib treatment without detectable genetic mutations might be identified by early 18 F-FDG PET (8). Similar results were obtained by Mileshkin et al (9), for whom best results were obtained for 18 F-FDG PET after 2 wk of erlotinib treatment in pretreated lung cancer patients.…”

“…Because only a few patients show any clinical benefit from erlotinib therapy, identification of the subgroup most likely to respond is a matter of pressing clinical importance to avoid ineffective treatment. 18 F-FDG PET has proven capable of predicting response to therapy with molecularly targeted agents (5)(6)(7)(8)(9). Preclinical models have shown the power of 39-deoxy-39- 18 F-fluorothymidine ( 18 F-FLT) PET to monitor early effects of the tyrosine kinase inhibitor erlotinib (10), and clinical studies have suggested that 18 F-FLT might predict response to both chemotherapy and molecularly targeted drugs (11,12).…”

Comparison of the diagnostic performance of 18F-fluorothymidine versus 18F-fluorodeoxyglucose positron emission tomography on pulmonary lesions: A meta analysis

“…All the seven studies included were prospective. In two studies, the study population underwent PET and PET/CT (13,25) and PET alone in the remaining studies (8,10,(19)(20)(21). The dose of FDG or FLT ranged considerably across the studies.…”

Volumetric and texture analysis of pretherapeutic 18F-FDG PET can predict overall survival in medullary thyroid cancer patients treated with Vandetanib

“…Changes in PET features for TKI response assessment and survival prediction have been evaluated in numerous previous studies. However, primarily SUV parameters (SUV peak , SUV max ) have been investigated for outcome prediction, e.g., in NSCLC treated with the TKI erlotinib [29][30][31]. Cook et al reported on heterogeneity assessment in NSCLC treated with the same TKI and the change of first-order parameters were correlated with survival [19].…”