Evaluation of Systemic Therapy for Advanced Melanoma
Authors:   , van Breeschoten Jesper 
Published: August 2023

The studies in this thesis aimed to provide insight in the real-world treatment patterns and outcomes of advanced melanoma patients in the Netherlands, to investigate the outcomes of BRAF V600-mutant and wild-type patients, to describe advanced melanoma care during the COVID-19 pandemic, and to assess and describe the added value of quality registries.

Chapter 2. Real-world outcomes of first-line ipilimumab plus nivolumab
Ipilimumab plus nivolumab is the most recent major addition of systemic therapies for the treatment of advanced melanoma. We observed that real-world patients receiving first-line ipilimumab plus nivolumab can achieve long-term survival, including patients with characteristics that were not represented in the clinical trial.

Chapter 3. Hospital variation survival outcomes of advanced melanoma patients
In 2014-2015, there was significant hospital variation in 2-year survival outcomes, even after correcting for case-mix and treatment with new systemic therapies. This significant variation may be caused by differences in uptake of new systemic therapies. From 2016 onwards, no significant differences in 2-year overall survival (OS) probabilities existed.

Chapter 4. Population mortality in advanced melanoma patients
In this chapter we investigate the relative contribution of population mortality in each response state for different age groups. Population mortality only played a large role for older patients alive at 1 year after diagnosis with a partial response (PR) or CR. Even though survival outcomes of advanced melanoma patients have improved over the last decade, the vast majority of patients still die due to melanoma-related mortality.

Chapter 5. Outcomes of advanced melanoma according to BRAF V600 status
Anti-PD-1 antibodies and BRAF/MEK inhibitors are the two main groups of systemic therapy in the treatment of BRAF V600-mutant advanced melanoma. Patients with BRAF V600-mutant disease are able to receive both systemic therapies while patients with BRAF V600 wild-type disease can only use anti-PD-1 antibodies. The results in this chapter suggest that advanced melanoma patients with BRAF V600 wild-type disease patients have worse survival compared to patients with a BRAF V600-mutant disease during the first 10 months after diagnosis because of less available treatment options.

Chapter 6. Comparison of anti-PD-1 and BRAF/MEK inhibitors
In Chapter 6, we compare survival outcomes of patients with starting with anti-PD-1 monotherapy versus BRAF/MEK inhibitors using propensity score matching to correct for case-mix factors. We found that after matching, patients receiving anti-PD-1 antibodies as a first-line treatment had a higher median and 2-year OS compared to patients treated with first-line BRAF/MEK inhibitors, 42.3 months versus 19.8 months and 85.4% versus 41.7%.

Chapter 7. Effects of COVID-19 on advanced melanoma care
In Chapter 7 we studied the impact of COVID-19 on advanced melanoma care in the Netherlands during the first two waves. The results in this chapter show that advanced melanoma care in the Netherlands was severely affected by the COVID-19 pandemic, especially in the south.

Chapter 8. End-of-life treatment
In Chapter 8 we describe the end-of-life treatment of advanced melanoma patients and present a quality indicator for end-of-life care in advanced melanoma. The results in this chapter show that even though a minority of Dutch advanced melanoma patients start a new systemic therapy of life, the percentages varied between centers.

Chapter 9. Linkage of systemic therapies to quality registries
One of the main downsides of quality registries is the registrational burden that is associated with them. To decrease this registrational burden, we describe a method to link declaration data from hospital pharmacies to the clinical data from quality registries in Chapter 9. The project shows that it is possible to gather and link declaration data of medicines to existing quality registries.