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Long-Term Outcomes in Patients with Metastatic Melanoma Treated with Anti-PD1 Therapy Based on PET Response

PET may have utility in predicting long term benefit and help guide discontinuation of therapy
28 Oct 2021
Cancer Immunology and Immunotherapy;  Diagnosis, Imaging and Staging;  Melanoma and other skin tumours

A team led by A/Prof Alexander M. Menzies of the Melanoma Institute Australia in North Sidney, NSW, Australia observed long-term outcomes in majority of patients with metastatic melanoma treated with anti-PD1-based therapy who remain progression-free at 1-year by RECIST/clinical grounds, and particularly in 75% of patients who achieve a complete metabolic response (CMR) on FDG-PET. In the minority of patients that progress, disease progression often occurs in solitary sites and is managed locally, with excellent overall survival. FDG-PET has a predominant role in predicting long-term benefit over CT, especially in patients with no complete response (CR). In those without CMR at 1-year, almost half will experience subsequent disease progression, such that a change in therapy could be implemented, whereas in CMR patients, FDG-PET may have a role in defining shorter treatment duration. The findings are published on 20 October 2021 in the Annals of Oncology.

The study team has previously shown the utility of FDG-PET to assess CMR in patients with metastatic melanoma treated with anti-PD1-based therapy (+/-CTLA4), reporting that 75% of patients who have not progressed by 1-year on RECIST or clinical grounds have CMR, including two-thirds of patients with RECIST partial response on CT. Patients with CMR have excellent medium-term survival, with progression seldom seen in 2 years. Of note, 77% of these patients had discontinued treatment after a median duration of treatment 21 months, including 26% within 12 months, and median follow-up after discontinuation was only 14.5 months. In the latest article published in the Annals of Oncology, they report extended follow-up to explore the 5-year outcomes based on PET response and the impact of early treatment discontinuation on long-term outcome.

The authors explained in the background that due to the mechanism of action of immune checkpoint inhibitors, the use of RECIST criteria can be challenging in response interpretation. FDG-PET scan, which captures the metabolic activity at tumour site, has shown an additional value over CT for staging in patients with melanoma and although CT scan remains standard-of-care, FDG-PET can be used synergistically in the assessment of treatment response and post-treatment surveillance.

In this study, the authors performed a retrospective analysis in 104 patients with baseline and 1-year PET and CT. They determined 1-year response by using RECIST for CT and EORTC criteria for PET. Progression-free survival (PFS) and overall survival (OS) were determined from the 1-year landmark.

At median follow-up of 61 months (range, 58-64) from 1-year PET, 94% remained alive and all but one had discontinued treatment after 23 months (median range, 1-59). Disease progression occurred in 19 patients (18%); in 10 (53%) while on treatment and in 12 (63%) in solitary sites for which 8 (67%) received local treatment. RECIST PFS rate at 5 years after PET was higher in those with CR compared to partial response (PR) / stable disease (SD) (93% vs 76%, respectively) and CMR compared to non-CMR (90% vs 54%, respectively). In patients with PR, 5-year PFS rate was superior in CMR (88% and 59%).

In total, 35 (34%) patients (14/29 in CR, 31/78 in CMR) discontinued treatment within 12 months, largely due to toxicity, with no impact on PFS rate compared to those that continued (84% vs 78%).

Despite progression events, the OS rate at 5-years was excellent and similar in patients with CR and PR/SD (100% vs 91%, respectively), CMR and non-CMR (96% vs 87%, respectively).

The authors concluded that 5 years after 1-year PET, sustained responses are observed in the majority of patients, particularly those with CMR. PET continues to predict progression better than CT, particularly in those patients with residual disease on CT. In the minority that progress, often in solitary sites and managed locally, the OS rate remains excellent. PET is effective in evaluating residual lesions on CT and can predict long-term benefit. The authors commented that studies confirming these findings in larger datasets, as well as the role of FDG-PET at even earlier intervals should be conducted.

Reference

Dimitriou F, Lo SN, Tan AC, et al. FDG-PET to predict long-term outcome from anti-PD1 therapy in metastatic melanoma. Annals of Oncology; Published online 20 October 2021. DOI: https://doi.org/10.1016/j.annonc.2021.10.003

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