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 mean decrease (in <5 lesions/patient) of >15% SUVmax. PFS was investigator-determined. Results: Of 74 erlotinib-treated patients, 51 completed all imaging assessments through d56; 13/51 (26%) FDG-evaluable patients had PMR at d14, as did 9/50 (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 EGFR mutations. D14 and d56 PMR by FDG or FLT were associated with improved PFS; hazard ratios for PET responders vs. non-responders were 0.3-0.4. D14 FDG-PET PMR was associated with improved OS (p=0.03) compared with FDG-PET non-responders. Conclusion: Early (d14) FDG-PET PMR is associated with improved PFS and OS, even in the absence of subsequent RECIST response. These data support inclusion of FDG-PET imaging in clinical trials testing novel targeted therapies, particularly those with anticipated cytostatic effects.
- Received October 15, 2010.
- Revision received January 31, 2011.
- Accepted February 15, 2011.
- Copyright © 2011, American Association for Cancer Research.