Background: Metastatic melanoma is a highly aggressive disease. The median survival in stage IV untreated dis- ease amounts to 6–9 months. Recent therapeutic devel- opments in immunotherapy and targeted therapy have shown markedly improved response and survival rates. The current project aims at determining the benefit of the introduction of these new molecules in advanced melanoma across several regions of Switzerland in real time setting.
Methods: This is a retrospective multi-center analysis of 395 Swiss advanced melanoma patients treated with standard chemotherapy, checkpoint inhibitors (anti CTLA-4 or anti-PD1 antibodies) and kinase inhibitors (BRAF inhibitors and MEK inhibitors) either in a first or second line setting from January 2008 until December 2014. Epidemiological, clinical and laboratory parameters such as gender, age at time of diagnosis, localization of the primary tumor, histological type, stage at first diagnosis, mutational status, LDH and S100 levels at first distant metastasis were collected.
Results: The median overall survival (mOS) from date of diagnosis of stage IV melanoma of all patients was 14.8 months (95% CI 13.5–18.2). The mOS of patients treated either with checkpoint or kinase inhibitors (n = 300, 21.2 months, 95% CI 18.8–25.3) was sig- nificantly longer (P < 0.001) compared to patients treated with standard chemotherapy (n = 95, 9.4 months, 95% CI 8.8–13.0). Survival at 1, 2 and 3 years was 71%, 52% and 38%, for patients treated with immunotherapy, and 55%, 32% and 24%, for targeted therapy, while patients treated with both immuno- and targeted therapy had survival rates of 89%, 63% and 49%, respectively. In contrast, the chemotherapy group showed rates of 40%, 16% and 8% at 1, 2 and 3 years. The progression-free survival (PFS) at 3 and 6 months was 26% and 11% for immunotherapy, compared to 79% and 47% for patients receiving kinase inhibitors and 44% and 31% for chemotherapy respec- tively. Baseline LDH levels in a normal range were associated with a better outcome in all treatment groups.
Conclusion: Treatment with checkpoint and kinase inhi- bitors beyond clinical trials significantly improves mOS in the real life setting, results that are consistent with published prospective trial data. Progression-free survival is significantly longer with kinase inhibitors compared to standard chemotherapy. Patients with baseline LDH levels within normal limits did significantly better in all treatment groups, which compares to prospective data from phase III clinical trials. National melanoma regis- tries and cancer statistics are useful for monitoring out- comes of approved therapies or newly established treatment protocols across multiple institutions and patient populations.
