Abstract
Simple SummaryImmunotherapy is the standard of care in patients harboring metastasized melanoma. However, once further tumor growth is stopped it remains unclear when immunotherapy can be safely ceased. This clinical question is increasingly raised especially in patients with a strong desire to discontinue therapy or in patients who are forced to pause treatment due to severe immune-related side effects. With our study we aim to provide data which may be helpful for clinicians and patients when treatment discontinuation is considered. Further prospective, multicenter studies are needed to further address this important clinical issue.Checkpoint inhibitors have revolutionized the treatment of patients with metastasized melanoma. However, it remains unclear when to stop treatment. We retrospectively analyzed 45 patients (median age 64 years; 58% male) with metastasized melanoma from 3 cancer centers that received checkpoint inhibitors and discontinued therapy due to either immune-related adverse events or patient decision after an (18F)2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) combined with a low-dose CT scan (FDG-PET-CT) scan without signs for disease progression. After a median of 21 (range 1–42) months of immunotherapy an FDG-PET-CT scan was performed to evaluate disease activity. In these, 32 patients (71%) showed a complete metabolic response (CMR) and 13 were classified as non-CMR. After a median follow-up of 34 (range 1–70) months, 3/32 (9%) of CMR patients and 6/13 (46%) of non-CMR patients had progressed (p = 0.007). Progression-free survival (PFS), as estimated from the date of last drug administration, was significantly longer among CMR patients than non-CMR (log-rank: p = 0.001; hazard ratio: 0.127; 95% CI: 0.032–0.511). Two-year PFS was 94% among CMR patients and 62% among non-CMR patients. Univariable Cox regression showed that metabolic response was the only parameter which predicted PFS (p = 0.004). Multivariate analysis revealed that metabolic response predicted disease progression (p = 0.008). In conclusion, our findings suggest that patients with CMR in an FDG-PET-CT scan may have a favorable outcome even if checkpoint inhibition is discontinued.
Highlights
Immune checkpoint inhibitors (ICI) are one of the most exciting anti-cancer treatments developed in oncology in the past decade
Patients with metastasized melanoma who have been treated with ICI in clinical routine at 3 German skin cancer centers were included into this retrospective study if the patients (i) had discontinued ICI treatment due to irAEs or their own wishes but not because of progressive disease and (ii) had received an fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)-computerized tomography (CT) scan just before or Cancers 2021, 13, x
(76%) patients were treated with checkpoint inhibition monotherapy (22 [49%] with pembrolizumab, 9 [20%] with nivolumab, 4 [9%] with ipilimumab) and 10 (22%) patients with combined immunotherapy
Summary
Immune checkpoint inhibitors (ICI) are one of the most exciting anti-cancer treatments developed in oncology in the past decade. Since their introduction, they have been used to treat various cancers with great success. Antibodies against cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) are important state-of-the-art treatments, for patients with metastasized skin cancer. These agents enable T-cells to outrun the escape mechanism of cancer cells and reattack the tumor. In the Checkmate 067 trial, 52% of patients were alive at 5 years under combined ipilimumab and nivolumab treatment, 44%
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