Treatment of melanoma of unknown primary in the era of immunotherapy and targeted therapy: A Dutch population-based study

Abstract

Melanoma of unknown primary (MUP) may have a different biology to melanoma of known primary, but clinical trials of novel therapies (e.g., immune checkpoint or BRAF/MEK inhibitors) have not reported the outcomes in this population. We therefore evaluated the overall survival (OS) among patients with MUP in the era of novel therapy. Data for stage III or IV MUP were extracted from a nationwide database for the period 2003-2016, with classification based on the eighth edition of the American Joint Committee on Cancer criteria. The population was divided into pre- (2003-2010) and post- (2011-2016) novel therapy eras. Also, OS in the post-novel era was compared between patients with stage IV MUP by whether they received novel therapy. In total, 2028 of 65,110 patients (3.1%) were diagnosed with MUP. Metastatic sites were known in 1919 of 2028 patients, and most had stage IV disease (53.8%). For patients with stage III MUP, the 5-year OS rates were 48.5% and 50.2% in the pre- and post-novel eras, respectively (p = 0.948). For those with stage IV MUP, the median OS durations were unchanged in the pre-novel era and post-novel era when novel therapy was not used (both 4 months); however, OS improved to 11 months when novel therapy was used in the post-novel era (p < 0.001). In conclusion, more than half of the patients with MUP are diagnosed with stage IV and the introduction of novel therapy appears to have significantly improved the OS of these patients.

Keywords: immunotherapy; melanoma; targeted therapy; unknown primary.

Figure 1

Overview of patients diagnosed with MUP in the Netherlands and corresponding changes in first‐line treatment use between 2003 and 2016. (a) the bar graph represents the absolute number of Dutch patients diagnosed with MUP during the study period, including those classified as stage III, stage IV, or not otherwise defined according to the eighth edition of the American Joint Committee on Cancer staging criteria. The curves show the numbers receiving novel therapy each year, while the percentages show the total percentages with MUP relative to all primary diagnoses of melanoma in the Netherlands for that year; (b) overview of first‐line treatment for patients in the Netherlands with stage III MUP; and (c) overview of first‐line treatment for patients in the Netherlands with stage IV MUP. Abbreviations: MUP, melanoma unknown primary. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Overall survival rates by stage, treatment era, and treatment type. Overall survival rates are shown for the following patient groups: (a) patients with stage III MUP in the pre‐ and post‐novel therapy eras; (b) patients with stage IV MUP in the pre‐ and post‐novel therapy eras, including those with and without novel therapy in the post‐novel era; (c) patients with stage IV MUP who received novel therapy in 2011–2012, 2013–2014, and 2015–2016 in the post‐novel therapy era; and (d) patients with stage IV MUP who received immunotherapy or targeted therapy first‐line in the post‐novel era. Abbreviations: MUP, melanoma unknown primary. [Color figure can be viewed at http://wileyonlinelibrary.com]