Retrospective analysis of treatment-naive Slovenian patients with metastatic melanoma treated with pembrolizumab – real-world experience

Abstract

BackgroundBased on recent data from clinical trials, the immune checkpoint inhibitor pembrolizumab prolongs survival and has a good toxicity profile in patients with advanced or metastatic melanoma. However, the question remains whether these results are transmitted into daily clinical practice. The aim of this study was to assess the efficacy and toxicity of pembrolizumab in treatment-naive patients with metastatic melanoma in everyday clinical practice in Slovenia and compare it to the results from clinical trials.Patients and methodsThis observational retrospective cohort study included 138 consecutive metastatic treatment-naive melanoma patients treated with pembrolizumab at the Institute of Oncology Ljubljana in Slovenia, from January 2016 to December 2018. Patient and treatment characteristics were retrospectively collected from hospital data base. Statistical data was obtained using the SPSS software version 22. Survival rate was calculated with the Kaplan-Meier method. Observation period took place between January 2016 and the end of June 2019.ResultsThe estimated median overall survival (OS) was 25.1 months (95% CI, 14.6–35.6) and the median progression-free survival (PFS) was 10.7 months (95% CI, 5.9–15.4). Among all patients, 29 (21.0%) achieved complete response, 31 (22.5%) partial response and 23 (16.7%) reached stable disease. The number of organs with metastatic involvement and the level of baseline lactate dehydrogenase (LDH) concentration had significant influence on survival rates. Immune-related adverse events (irAE) were reported in 88 (63%) patients, while grade 3–4 irAE occurred in 12 (8.7%). Due to toxicity, 16 (11.6%) patients discontinued the treatment.ConclusionsOur real-world data from single centre retrospective analysis of treatment-naive metastatic melanoma patients treated with pembrolizumab showed inferior median OS and similar median PFS, compared to the results from clinical trials. However, patients with normal serum levels of LDH and a small number of organs with metastatic involvement had comparable survival outcomes. Toxicity rates of pembrolizumab were quite similar. These results further support the use of pembrolizumab for metastatic treatment-naive melanoma patients.

Real-World Therapy with Pembrolizumab: Outcomes and Surrogate Endpoints for Predicting Survival in Advanced Melanoma Patients in Germany

“…The median OS (30.5 months) and 2-year survival rate (55.4%) were found to be higher in this study compared to previous reports of the median OS, ranging from 19.4 to 30 months [ 16 , 18 , 20 ], and the 2-year survival rates (48% and 44%) reported by others [ 16 , 18 ]. A lower proportion of patients with a poor ECOG score in the present study may explain these differences from RWE studies with poorer OS outcomes.…”

“…Real-world evidence (RWE) on pembrolizumab in US samples has shown median OS rates between 19.4 and 30 months [ 16 , 17 , 18 , 19 ] and a median real-world progression-free survival (rwPFS) of 4.2 months [ 19 ]. Recent RWE data on pembrolizumab from Slovenia showed a comparable median OS of 25.1 months, with a median rwPFS of 10.7 months [ 20 ]. Improvements in OS have been reported after the introduction of PD-1 inhibitors in Germany [ 21 ]; however, detailed insights on real-world outcomes related to pembrolizumab are still lacking.…”

Adverse events during immunotherapy in Slovenian patients with metastatic melanoma reveal a positive correlation with better treatment outcomes

“…Ipilimumab is a fully humanized anti-CT-LA-4 monoclonal antibody; pembrolizumab and nivolumab are humanized monoclonal anti-programmed cell death-1 (PD-1) antibodies. [11][12][13] With the use of CTLA4 inhibitors or anti-PD1 antibodies, also called checkpoint inhibitors, as monotherapy or in combination (nivolumab and ipilimumab), the increased risk of immune-related lung, intestinal, liver, kidney, skin, or endocrine adverse events persists. [11][12][13][14] Due to the severity of the ad- irAE cohort = patients with metastatic melanoma that developed immune-related adverse events during immunotherapy; M1a/b = distant metastasis to skin, soft tissue including muscle and/or nonregional lymph node and lungs; NirAE cohort = patients with metastatic melanoma that did not develop immune-related adverse events during immunotherapy; FIGURE 10.…”

“…[11][12][13] With the use of CTLA4 inhibitors or anti-PD1 antibodies, also called checkpoint inhibitors, as monotherapy or in combination (nivolumab and ipilimumab), the increased risk of immune-related lung, intestinal, liver, kidney, skin, or endocrine adverse events persists. [11][12][13][14] Due to the severity of the ad- irAE cohort = patients with metastatic melanoma that developed immune-related adverse events during immunotherapy; M1a/b = distant metastasis to skin, soft tissue including muscle and/or nonregional lymph node and lungs; NirAE cohort = patients with metastatic melanoma that did not develop immune-related adverse events during immunotherapy; FIGURE 10. Difference in progression free survival between the irAE and NirAE cohort with M1c and M1d (M1c/d) patients, with a significant increase in the survival probability of almost 70% for NirAE cohort to less than 50% for irAE cohort.…”

“…11 , 12 , 13 With the use of CTLA4 inhibitors or anti-PD1 antibodies, also called checkpoint inhibitors, as monotherapy or in combination (nivolumab and ipilimumab), the increased risk of immune-related lung, intestinal, liver, kidney, skin, or endocrine adverse events persists. 11 , 12 , 13 , 14 Due to the severity of the adverse events caused by immunotherapy treatment, in some cases, discontinuation of the treatment is required. It has been shown that an early discontinuation of immunotherapy due to an adverse event does not negatively affect the long-term survival among these patients.…”