Early FDG PET/CT Scanning May Predict Treatment Response in Melanoma

Despite positive signs, limitations of this study include a small sample size within a single institution, and no patients with stable disease were included. In addition, there was variability in the time between scans for patients, as well as a difference in the scans that were used.

Early ¹⁸F-fluorodeoxyglucose (FDG)- PET/ CT imaging may identify metabolic changes that correspond with treatment response and progression-free survival (PFS) in patients with advanced melanoma receiving pembrolizumab (Keytruda), according to an observational study (NCT02791594) published in Clinical Cancer Research.¹

A metabolic flare (MF) or a metabolic response (MR) was identified in 6 of 11 (55%) responders and 0 of 8 (0%) non–responders, with an objective response rate (ORR) of 100% in the MF-MR group and an ORR of 38% in the stable metabolism (SM) group. The overall survival at 3 years was 83% in the MF-MR group compared with 62% in the SM group. Median PFS was more than 38 months (median not reached) in the MF-MR group and 2.8 months (95% CI, 0.3-5.2) in the SM group (P = 0.017).

“While the results need to be validated, this has the potential to be broadly applicable and offer physicians the ability to deescalate therapy or avoid surgery in patients who are responding, identify non–responders who may need an escalation of therapy, and be used in phase I clinical trials to test if a therapy is working,” Michael D. Farwell, MD, associate professor of radiology at the Hospital of the University of Pennsylvania and lead study author, said in a press release regarding the study.²

This trial consisted of 19 patients with advanced melanoma who were scheduled to receive pembrolizumab. FDG PET/CT imaging was conducted at baseline and then again 1 week after starting treatment with pembrolizumab. Enrollment on trial was contingent on having at least 1 measurable lesion and no previous anti–PD-1 or anti–PD-L1 therapies.

The scans were analyzed for changes in maximum standardized uptake value (SUV_max). MF was defined as an increase in tumor SUV_max of over 70%, and MR was defined as a decrease in tumor SUV_max of less than 30%.

Farwell explained that this trial was based off a hypothesis that states that patients experience metabolic changes in tumors after a week of therapy. When a patient responds to immunotherapy, activated immune cells infiltrate into the tumor, so the scans are expected to first show an MF, or an increase in FDG activity, according to Farwell.

“If you’re [prescribing] imaging after 3 weeks, you’re unlikely to catch this flare, because the response to immunotherapy happens so quickly and, in some cases, it’s already done—there’s no tumor left,” Farwell explained in the press release. “The other nice thing about imaging at 1 week is we are looking at this response curve over a pretty short interval. If you wait to monitor progress over longer intervals, it means the tumor has more time to grow in non–responders, which can complicate the analysis.”

Despite positive signs, limitations of this study include a small sample size within a single institution, and no patients with stable disease were included. In addition, there was variability in the time between scans for patients, as well as a difference in the scans that were used.

Other challenges that Farwell points to are the observation of heterogeneity among lesions in the same patient and the uncertainty of whether a tumor with stable metabolism is responding but is in between reaction phases. Potential solutions for this could include adding additional studies, such as blood tests, CD8 PET scans, or serial FDG PET/CT imaging, to analyze the change over time.

References

1. Anderson TM, Chang BH, Huang AC, et al. FDG PET/CT imaging 1 week after a single dose of pembrolizumab predicts treatment response in patients with advanced melanoma. Clin Cancer Res. 2024:OF1-OF10. doi:10.1158/1078-0432.ccr-23-2390
2. FDG PET/CT imaging after just one week may predict treatment response in patients with advanced melanoma. News release. American Association for Cancer Research. January 24, 2024. Accessed January 30, 2024. http://tinyurl.com/484c8s2v