by Dr. C.H. Weaver M.D, updated 2/2019
The U.S. Food and Drug Administration (FDA) has approved Keytruda for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete surgical resection.
Adjuvant Therapy in Melanoma
Melanoma is separated into five staging categories (stages 0-4). Stage III melanoma is a cancer that has spread to the regional lymph nodes but has not yet spread to distant lymph nodes or to other parts of the body (metastasized). Current standard treatment of stage III melanoma is surgical resection of the primary tumor as well as the involved lymph nodes. Despite surgical removal of the cancer however, most patients experience disease recurrence and progress to metastatic disease. By five years, the majority of stage IIIb and IIIc patients (68% and 89%, respectively) experience disease recurrence. There remains an unmet need for adjuvant therapy administered following surgery to reduce the risk of the cancer spreading.
The KEYNOTE-054 clinical trial evaluated adjuvant therapy with Keytruda compared to placebo in patients with resected high-risk stage IIIA, B, or C melanoma. In total, the study enrolled 1,019 patients who were treated with either Keytruda or a placebo for up to 1 year. This represents a total of 18 outpatient administrations.
The FDA approval was based on results from the KEYNOTE-054 trial phase 3 clinical trial, which demonstrated that Keytruda improved recurrence-free survival by reducing the risk of disease recurrence by 43 percent in individuals with surgically resected, high-risk stage III melanoma.
Keytruda is the second “checkpoint inhibitor” demonstrated to improve the treatment of stage III melanoma. The United States Food and Drug Administration recently granted approval to Opdivo (nivolumab), another “checkpoint inhibitor” for the adjuvant treatment of melanoma. Opdivo significantly improved recurrence-free survival at 18 months (66%) compared to standard treatment with Yervoy® (ipilimumab), (53%) in patients with surgically resected Stage III or Stage IV melanoma.
Keytruda and Opdivo are both precision cancer medicines that belong to a new class of medicines called PD-1 inhibitors that have generated great excitement for their ability to help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 may enhance the ability of the immune system to fight cancer. These so call “checkpoint inhibitors” work by blocking PD-1. Additional clinical trials will further evaluate how best to use these new medications; whether best used alone, or in combination, and the optimal duration of therapy remain unanswered questions.