Early Imaging Can Identify Positive Immunotherapy Responders in Advanced Melanoma

Combining positron emission tomography (PET) and computed tomography (CT) early in the treatment plan for patients diagnosed with advanced melanoma can help identify the potential benefit of a specific immunotherapy therapy and avoid the risk of non-beneficial intervention, acording to a new study.

Physicians now have access to multiple immune checkpoint inhibitors (ICIs) as a treatment option for melanoma; these drugs include ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab. However, the distinct mechanism of action of these drugs often complicates efficacy assessment. This has led to the incorporation of immune-based response criteria in clinical trials for cancer immunotherapies.

In their study, the authors evaluated ¹⁸F-fluorodeoxyglucose (FDG) PET/CT scanning as an early predictor of response to ICI in patients with advanced melanoma. The prospective trial involved serial ¹⁸F-FDG PET/CT imaging in 20 patients with advanced melanoma undergoing ICI therapy. Trial analyses included characterization of changes in tumor burden and functional parameters, and the data were used to develop criteria to predict eventual clinical response to therapy.

“Current anatomic CT-based response criteria are typically performed at the earliest 2 to 4 months into treatment and are limited in their ability to assess stable disease and pseudoprogression,” said Steve Y. Cho, MD, one of the lead authors on the study, in a press release.

Patients underwent 3 scans: before treatment initiation (SCAN-1), at days 21 to 28 (SCAN-2), and at 4 months (SCAN-3). Tumor response at each time point following treatment was assessed according to RECIST 1.1, immune-related response criteria, PERCIST (PERCIST 1.0), and European Organization for Research and Treatment of Cancer (EORTC) criteria.

Of the 20 evaluable patients, 16 were treated with ipilimumab, 3 received BMS-936559, and 1 received nivolumab. The best overall response at 4 months or more was complete response (n = 2), partial response (n = 2), stable disease (n = 1), and progressive disease (n = 15). When the authors analyzed the response at SCAN-2, RECIST 1.1, immune-related response criteria, PERCIST, and EORTC criteria demonstrated accuracies of 75%, 70%, 70%, and 65%, respectively.

“When ¹⁸F-FDG PET-based response criteria were combined with CT-based criteria, we were able to more accurately differentiate eventual clinical benefit. Based on our data, we have proposed a combined PET and CT-based response criteria to immune-checkpoint inhibitor therapy in advanced metastatic melanoma. Interestingly, we found a small increase in 18F-FDG tumor uptake at this early time point that may implicate an active immune mediated 'flare' as a good indication that the tumor is responsive to the immune therapy,” Cho said.

“Combining functional and anatomic imaging parameters from 18F-FDG PET/CT scans performed early in ICI appears predictive for eventual response in patients with advanced melanoma,” the authors wrote. They recommend validation of their results in larger studies.

Reference

Cho SY, Lipson EJ, Im HJ, et al. Prediction of response to immune checkpoint inhibitor therapy using early-time-point 18F-FDG PET/CT imaging in patients with advanced melanoma. J Nucl Med. 2017;58(9):1421-1428. doi: 10.2967/jnumed.116.188839.