A Randomized Phase 3 Study of Management of Treatment Naive Primary Melanoma in Elderly Patients

Melanoma is the fifth most common cancer diagnosed in both men and women in the United States. Almost 40% of patients diagnosed with melanoma are over the age of 70, and older age is strongly correlated with a poorer prognosis and higher mortality. Older patients are also more likely to have competing comorbidities that further complicate their treatment planning and causes of mortality. Despite this, there is a lack of prospective data on how to best manage the disease in this patient population. The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) aims to fill this knowledge gap by conducting the phase 3 EA6244 clinical trial.

The standard treatment for early-stage melanoma, regardless of age, is based on tumor thickness. Patients with a thinner tumors (<0.8 mm) and no other high-risk features will have wide local excision (WLE) surgery to remove the cancer and a margin of healthy-looking tissue around all of its edges. For thicker tumors (≧ 0.8 mm), patients will typically also undergo a sentinel lymph node biopsy (SLNB). The main purpose of this separate surgical procedure is to find, remove, and test the first, or sentinel, lymph node where cancer is most likely to spread.

However, given older patients’ complicated comorbidities and potential frailty, aggressive treatment for melanoma may not lead to improved quality of life. Less intensive treatment that forgoes a SLNB in favor of node surveillance may spare patients the costs and recovery from an additional surgery without increased risk of recurrence or death.

The hypothesis of EA6244 is that older patients who do not undergo a SLNB in addition to the standard WLE will have similar recurrence-free survival rates as patients who do undergo the biopsy. The study investigators also hypothesize that this less intensive management will result in better patient-reported outcomes. EA6244’s primary endpoints are recurrence-free survival and patient-reported outcomes (PROs).

After enrolling in EA6244, participants will complete a baseline Geriatric Assessment (GA) to evaluate their overall health and quality of life (QOL). Patients will then be randomized 1:1 to either WLE and SLNB or WLE only. After surgery, patients will be seen for surveillance visits every 4 months for the first 2 years, which will include nodal basin evaluations as needed and QOL assessments. During that time, they may receive any adjuvant therapy at the investigator’s discretion, including standard-of-care regimens or investigational therapy through another clinical trial. They will repeat GAs at 1 and 2 years. Follow-up will last 5 years, with visits every 6 months during years 2-5. They will complete a GA if the cancer recurs during the study period.

All patients who participate in EA6244 must be at least 75 years of age, have newly diagnosed primary cutaneous melanoma, be eligible for WLE surgery, and have a SLNB indicated. Patients for whom the SLNB is not indicated, or for whom it would be difficult or impossible to perform, are not eligible.

This study will provide valuable data on an underrepresented population of older patients with early-stage melanoma who have well-described competing causes of mortality. By emphasizing PRO measures throughout the study and including them as a co-primary endpoint, researchers will gain a better understanding of the factors that directly influence treatment tolerance and outcomes in these patients.

The study chair for this trial is Yana Najjar, MD (University of Pittsburgh/UPMC Hillman Cancer Center) and the co-chair is Rino Seedor, MD (Thomas Jefferson University/Sidney Kimmel Comprehensive Cancer Center).