Real-World Treatment Impact of Newer Agents on Survival of Patients With Metastatic Melanoma
The approval of several new agents for metastatic melanoma in the past several years has led to changes in how the disease is treated and managed. Treatments such as the programmed cell death protein 1 (PD-1) inhibitors pembrolizumab, ipilimumab, and nivolumab; BRAF inhibitors; and MEK inhibitors have initiated a paradigm shift in the treatment of metastatic melanoma. However, the phase III trials that led to the approvals of these agents represent a small percentage of the real-world metastatic melanoma patient population.
In a retrospective, population-based study, researchers sought evidence that major changes in the management of metastatic melanoma have led to improved survival for patients whether or not they met the eligibility criteria for pivotal clinical trials that led to development of new agents in the disease. Their findings were published by Donia et al in the European Journal of Cancer.
The researchers wrote, “It is not uncommon for clinicians to treat patients with metastic melanoma who do not precisely fit the criteria of pivotal clinical trial participation. It is a matter of debate whether the results from these trials can be applied to the entire population of patients with metastatic melanoma, as strong evidence of efficacy in the ‘trial-excluded’ patient populations of metastatic melanoma is lacking.”
Methods
The researchers used the Danish Metastatic Melanoma database (DAMMED) to retrieve all metastatic melanoma cases (excluding ocular) diagnosed in 3 nonconsecutive years marked by major changes in first-line treatment— 2012: interleukin-2 and BRAF inhibitors; 2014: anti–cytotoxic T-lymphocyte antigen 4 (CTLA-4); and 2016: anti–PD-1 and MEK inhibitors. Patients were grouped into “trial-like” and “trial-excluded” groups based on the following criteria:
- Eastern Cooperative Oncology Group/World Health Organization performance status > 2
- Active brain or leptomeningeal metastases
- Any serious or uncontrolled medical conditions
- Autoimmune diseases
- Previous malignancies in the past 3 years
- Immunosuppressive medications
- Unmeasurable disease according to Response Evaluation Criteria in Solid Tumors, version 1.1.
Results
In the trial-like group—39% of the all the cases of metastatic melanoma in the database—the median overall survival was not reached in 2016 vs 18.8 months in 2014 (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.35–0.75, P = .0005) and 16.5 months in 2012 (HR = 0.41, 95% CI = 0.27–0.63; P = .0001).
In the trial-excluded group—61% of all cases of metastatic melanoma in the database—the median overall survival was 6.9 months in 2016 vs 5.2 months in 2014 (HR = 0.66, 95% CI = 0.52–0.84; P = .0008) and 4.2 months in 2012 (HR = 0.66, 95% CI 0.52–0.84, P = .0007). Seventy-five percent of patients in the trial-excluded group had brain metastases and/or a performance status ≥ 2.
In a subgroup analysis of patients with a BRAF wild-type mutation, there was an improved 1-year survival rate in 2016 vs 2014—35.9% vs 18.8%.
The authors concluded, “The introduction of modern treatments has led to an improved survival of real-world patients with metastatic melanoma, regardless of their eligibility to clinical trials and the BRAF status. These data support the application of modern treatments to patient populations that are not represented in pivotal trials.”
Disclosure: The study authors' full disclosures can be found at ejcancer.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
