In a Danish retrospective study reported in the International Journal of Cancer, Ellebaek et al found that patients with advanced melanoma responding to PD-1 inhibitor therapy who stopped treatment within 18 months had improved survival outcomes when fluorodeoxyglucose (F-18) positron-emission tomography (FDG-PET) scans were negative at the time of stopping therapy. The findings suggest the possibility of early discontinuation of treatment in this setting based on FDG-PET findings.
As stated by the investigators, “Routine FDG-PET may help predict clinical outcomes after response to immunotherapy. With a European Medicines Agency–recommended treatment length until disease progression or unacceptable toxicity, the optimal duration of immunotherapy remains to be defined.”
Study Details
The study involved data from the Danish Metastatic Melanoma Database on patients with partial or complete response on PD-1 inhibitor therapy based on serial FDG-PET/computed tomography scans who stopped treatment at ≥ 4 months to < 18 months without disease progression. Of the total of 140 patients included in the analysis, 92 discontinued treatment due to physician’s or patient’s choice in the absence of treatment-limiting toxicities (elective discontinuation group), and 48 stopped therapy due to treatment-limiting toxicities (toxicity discontinuation group).
Patients with metastatic melanoma who obtain an early response and early discontinue immunotherapy have an excellent prognosis, especially in the absence of FDG-PET–avid lesions when discontinuing treatment. These data support the option of early discontinuation, limiting possible overtreatment and thereby toxicity, health, and economic expenses and improving logistics.— Ellebaek et al
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Key Findings
At a median follow-up of 29.3 months, 93% of patients in the elective discontinuation group vs 75% of the toxicity discontinuation group remained alive (hazard ratio [HR] = 0.19, 95% confidence interval [CI] = 0.07–0.53, P = .0013), with the elective discontinuation group also having significantly better melanoma-specific survival (HR = 0.07, 95% CI = 0.02–0.32, P = .0005).
At the time of treatment discontinuation, 31 patients had FDG-PET–avid lesions and 109 did not. Patients without vs with FDG-PET–avid lesions had significantly better overall survival (HR = 0.08, 95% CI = 0.02–0.24, P < .0001) and melanoma-specific survival (HR = 0.03, 95% CI = 0.01–0.17, P < .0001). On multivariate analysis of melanoma-specific survival, FDG-PET–negative status was the sole independent predictor of outcome (HR = 0.07, 95% CI = 0.01–0.42, P = .004).
Among the 92 patients in the elective discontinuation group, 13 had FDG-PET–avid lesions and 79 did not at time of treatment discontinuation. Patients without vs with FDG-PET–avid lesions had significantly improved overall survival (HR = 0.006, 95% CI = 0.0–0.10, P = .0004) and melanoma-specific survival (HR = 0.0008, 95% CI = 0.00–0.23, P = .0137).
The investigators concluded, “Patients with metastatic melanoma who obtain an early response and early discontinue immunotherapy have an excellent prognosis, especially in the absence of FDG-PET–avid lesions when discontinuing treatment. These data support the option of early discontinuation, limiting possible overtreatment and thereby toxicity, health, and economic expenses and improving logistics.”
Marco Donia, MD, PhD, of the Department of Oncology, National Center for Cancer Immune Therapy, Copenhagen University Hospital, is the corresponding author for the International Journal of Cancer article.
Disclosure: The study was supported by the Herlev and Gentofte Research Council and The National Board of Health. The Danish Metastatic Melanoma Database is supported by Merck Sharp and Dohme, Bristol Myers Squibb, Novartis, and Pierre Fabre. For full disclosures of the study authors, visit onlinelibrary.wiley.com.
