Immune-checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic melanoma. Ipilimumab and Ipilimumab-Nivolumab combination therapies were approved by the United States Food and Drug Administration in 2011 and 2015, respectively. We aimed to evaluate potential changes in the survival of patients with metastatic melanoma following the approval of these agents.
We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database (Nov 2021 submission). All patients aged 20 and above who were diagnosed with ‘distant’ melanoma (per ‘combined summary stage’) from 2007 through 2018 were included in the study. This time period was further sub-categorized into 2007–2010 (pre-ICI era), 2011–2014 (single-agent ICI era), and 2015–2018 (combination ICI era) based on the approval timeline of ICI.
The median overall survival (OS) was 8, 10, and 14 months in the pre-ICI, single-agent ICI, and combination ICI eras respectively (log-rank test, χ² = 189.03, p < 0.001). On Cox-proportional hazard analysis, patients diagnosed in the single-agent and combination ICI eras had a significantly lower risk of dying [HR 0.82 (95% CI 0.78–0.87) and 0.67 (0.64–0.71), respectively] compared to patients diagnosed in the pre-ICI era. Patients who were of the male gender, aged ≥ 65 years, and those receiving chemotherapy and/or radiotherapy were at a significantly higher risk of dying. Married individuals had a significantly lower risk of dying compared to patients who were divorced, separated, or widowed at the time of diagnosis. There was no significant difference in survival demonstrated among non-Hispanic blacks versus non-Hispanic whites.
Survival of patients with metastatic melanoma has improved in the era of immune checkpoint inhibitors. It implies that the survival of patients reported in trials can be correlated at a population level as well. Future analysis from the SEER database is needed when new data becomes available to see if there is a further increase in OS.
- • Significant improvement in median survival in the era of Immune checkpoint inhibitors.
- • No significant difference in survival among black versus white population.
- • Significant lower risk of dying among married individuals.
Melanoma develops from melanocytes in the skin, mucosa, and eye. Melanoma of the skin accounts for an estimated 5% of all new cancer cases in the United States, with 7650 deaths expected to be directly related to melanoma in 2022 . Historically, advanced melanoma has been difficult to treat and in 2004, no systemic therapies had been shown to provide a survival benefit . However, over the last decade, there has been an improvement in the survival of patients with advanced melanoma . This success has largely been attributed to the development and subsequent implementation of immune checkpoint inhibitors (ICI) and other targeted therapies .
Ipilimumab, an anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) fully human monoclonal antibody, yielded significant improvement in the median overall survival of patients with metastatic melanoma (10 months among those receiving ipilimumab plus gp100, versus 6.4 months among patients receiving gp100 alone) . Thus in 2011, ipilimumab became the first ICI to be approved by the United States Food and Drug Administration (FDA) for the treatment of patients with newly diagnosed or previously-treated metastatic melanoma .
Nivolumab, an anti-programmed death 1 (PD-1) antibody, was later found to significantly prolong progression-free survival when compared to ipilimumab both alone and in combination with the aforementioned . This dual regimen was subsequently approved in 2015 and has since become the standard of care for patients with advanced melanoma , .
The improved overall survival of patients with advanced melanoma following the advent of ICI has been well established in clinical trials . However, population-based studies to evaluate the impact of these landmark therapies are lacking. Therefore, we conducted a study to assess for changes in median survival of this patient population over time using the Surveillance, Epidemiology, and End Results ( SEER) database.
Previous research was done by Uprety et.al using SEER data up to 2014 to compare the 2-year OS between pre and post-targeted eras . However, in 2015, therapy with combination ICI was approved. The impact on OS with the approval of combination ICI is yet to be evaluated using the SEER database. To our knowledge, this is the first population-based study to compare the survival of patients in the era of ICI after the approval of combination ICI.