FDG PET/CT Imaging Performed After 1 Week of Immunotherapy May Predict Treatment Response in Patients With Advanced Melanoma
A prospective pilot study investigating the use of early fluorodeoxyglucose F-18 (FDG) positron-emission tomography/computed tomography (PET/CT) in patients with advanced melanoma has found that metabolic changes in melanoma metastases detected on early FDG PET/CT imaging are potentially predictive of response to pembrolizumab—and significantly correlated with progression-free survival. The study was published by Anderson et al in Clinical Cancer Research.
Although cancer immunotherapy has transformed the standard of care for many patients with cancer, not every patient responds to the therapy, and treatment can cause severe immune-related adverse events that may be permanent or even life-threatening, studies show. This new finding by Anderson et al has the potential to enable personalized treatment of patients on cancer immunotherapy, which could improve outcomes and reduce unnecessary side effects from ineffective treatment, according to the study authors.
The researchers enrolled 21 patients with advanced melanoma scheduled to begin treatment with pembrolizumab between November 2016 and November 2019. Patients were required to have at least one measurable lesion and could not have received previous anti–PD-1 or anti–PD-L1 therapies. FDG PET/CT imaging was performed on each patient within 4 weeks prior to initiation of pembrolizumab and again about 1 week after the first dose of pembrolizumab. Two patients did not complete both imaging scans, and their results were excluded from the study.
FDG PET/CT scans were evaluated for changes in maximum standardized uptake value (SUVmax), and thresholds were identified by receiver operating characteristic analysis. Metabolic flare was defined as a > 70% increase in tumor SUVmax and metabolic response was defined as a > 30% decrease in tumor SUVmax.
- Metabolic changes in melanoma metastases on early FDG PET/CT imaging are potentially predictive of response to pembrolizumab and are correlated with progression-free survival.
- Early identification of responding patients could enable de-escalation of therapy, which could decrease morbidity and increase quality of life in patients.
The researchers found that a metabolic flare or response was identified in 6 of 11 (55%) responders and in 0 of 8 (0%) nonresponders, with an objective response rate of 100% in the metabolic flare or response group and an objective response rate of 38% in the stable metabolism group. A metabolic flare or response was associated with T-cell reinvigoration in the peripheral blood and immune infiltration in the tumor.
Overall survival at 3 years was 83% in the metabolic flare or response group and 62% in the stable metabolism group. Median progression-free survival was > 38 months (median = not reached) in the metabolic flare or response group and 2.8 months (95% confidence interval = 0.3–5.2) in the stable metabolism group (P = .017).
“Early FDG PET/CT can identify metabolic changes in melanoma metastases that are potentially predictive of response to pembrolizumab and significantly correlated with progression-free survival,” concluded the study authors.
Potential Clinical Significance
“While the results need to be validated, this has the potential to be broadly applicable and offer physicians the ability to de-escalate therapy or avoid surgery in patients who are responding [to treatment], identify nonresponders who may need an escalation of therapy, and to be used in phase I clinical trials to test if the therapy is working,” said Michael D. Farwell, MD, Associate Professor of Radiology at the Hospital of the University of Pennsylvania and senior author of this study, in a statement.
Disclosure: Funding for this study was provided by the Investigator Studies Program of Merck Sharp & Dohme LLC, ImaginAB, the National Cancer Institute, the RSNA Resident/Fellow Research Grant, the Tara Miller Melanoma Foundation, the Melanoma Research Alliance, the David and Hallee Adelman Immunotherapy Research Fund, and the Parker Institute for Cancer Immunotherapy Bridge Scholar Award. For full disclosures of the study authors, visit aacrjournals.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.