Molecular Imaging of Tumor Metabolism Predicts Lung Cancer Response to Immunotherapy

Molecular imaging of tumor glucose metabolism might be a prognostic biomarker of non-small cell lung cancer (NSCLC) responses to the investigational immunotherapy agent atezolizumab (Tecentriq), according to a multicenter study by Genentech, presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 63^rd Annual Meeting, held June 11-15, 2016, in San Diego.

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging of patients undergoing immunotherapy with atezolizumab appears to offer prognostic utility “similar to what has been reported with conventional chemotherapeutic treatments, with early metabolic response predicting subsequent benefit,” the authors reported.

However, FDG-PET scans did not differentiate tumor pseudoprogression from sustained disease progression, they cautioned.

The findings “help define the potential role of FDG-PET as a prognostic and predictive biomarker in the treatment of lung cancer with such immunotherapeutics,” said Jill Fredrickson, PhD, a clinical imaging scientist at the Department of Early Clinical Development at Genentech, San Francisco, in a SNMMI news release.

FDG-PET uses a radiolabeled glucose (sugar) tracer to visualize tumors’ metabolic activity. Tumors’ metabolically active volumes can be quantified using FDG-PET imaging data.

Atezolizumab is an investigational humanized monoclonal antibody that targets the programmed death ligand 1 (PD-L1) protein in order to restore immune T cells’ antitumor activity.

The phase II, single-arm, 3-cohort FIR trial (NCT01846416) was undertaken to assess atezolizumab’s activity in patients whose NSCLC tumors express PD-L1. As part of this trial, the prognostic and treatment response monitoring utility of FDG-PET was assessed. The authors also sought to determine if tumor pseudoprogression-initial increases in tumor burden early in the antitumor T-cell response triggered by immunotherapy-can be differentiated from true disease progression.

A total of 138 patients with NSCLC were administered atezolizumab (1200 mg, intravenously) at 3-week intervals, and FDG-PET imaging was used to quantify whole-body metabolic tumor burden (tumor glucose uptake and retention) at baseline and after 6 weeks of treatment. Scans were also acquired upon disease progression. European Organisation for Research and Treatment of Cancer (EORTC) criteria were used.

Of the 138 study participants, 103 had evaluable images for baseline and at least one post-baseline visit.

“Baseline whole-body metabolic tumor burden was a significant negative prognostic marker for overall survival, more so than baseline sum of longest dimensions of target lesions based on diagnostic computed tomography,” the authors reported. “Patients with metabolic response by EORTC criteria on 6-week scans had a higher objective response rate” (ORR: 73.9% [17/23] versus 6.3% [5/80] for nonresponders).

Baseline FDG-PET SUV_max, a measure of tumors’ FDG (glucose)-uptake avidity, was not prognostic, however. Nor was a measure of baseline FDG uptake and retention (retention index [RI]), or changes in RI between PET scan acquisitions.

“Response after apparent radiographic progression was seen in only two patients, so the utility of FDG-PET to distinguish pseudoprogression could not be determined,” the study authors reported.