Trial Results Show Improved Distant Metastasis-Free Survival With Pembrolizumab in Melanoma

In an email with Pharmacy Times, Scot Ebbinghaus, MD, vice president of oncology clinical research at Merck, discussed the growing body of research surrounding pembrolizumab (Keytruda) and new data from the KEYNOTE-716 trial in completely resected stage IIB or IIC melanoma.

Keytruda has so many indications at this point—can you start by reviewing its key uses and what it’s being investigated for?

Keytruda is foundational in the treatment of many advanced cancers. Keytruda is approved in the U.S. for 33 indications across 16 tumor types, plus 2 tumor-agnostic indications, and more than 1 million patients have been treated with Keytruda worldwide.

We have made significant progress in demonstrating the impact of our medicines in many hard-to-treat metastatic cancers, and we are building on this knowledge to continue to improve outcomes for people with cancer. We have an expansive program investigating Keytruda in earlier lines of therapy, with approximately 20 ongoing registrational studies across multiple types of cancer, including melanoma, lung and renal cell carcinoma. We are working to enhance the immune response to Keytruda with combination therapies that target complementary pathways, including investigational checkpoint inhibitors targeting LAG-3, CTLA-4, TIGIT, and ILT4.

What is distant metastasis-free survival (compared to overall survival or other measures), and why it is important to investigate this outcome in melanoma?

The trial’s key secondary endpoint of distant metastasis-free survival (DMFS) was defined as time from randomization to the first diagnosis of distant metastasis. The goal of investigating adjuvant treatment in melanoma is to help prevent disease recurrence, especially distant metastases, because patients often face a significantly worse long-term prognosis when melanoma spreads to distant sites; the development of metastases is generally associated with death from cancer, including for patients with melanoma.

The KEYNOTE-716 trial is continuing and will be evaluated for the key secondary endpoint of overall survival in upcoming analyses. 

What did the KEYNOTE-716 trial find with regard to distant metastasis-free survival?

Keytruda as adjuvant therapy demonstrated a statistically significant and clinically meaningful improvement in DMFS versus placebo (HR=0.64 [95% CI, 0.47-0.88]; p=0.0029) in patients with stage IIB and IIC melanoma, at a median follow-up of 27.4 months. This translates into a reduction of 36% in the risk of developing distant metastases.

How does this finding underline the need for adjuvant therapy in melanoma?

Patients with stage IIB and IIC melanoma can have a high risk of recurrence after surgery and similar 5-year survival outcomes as those with stage IIIB disease, for whom adjuvant treatment is standard of care. New treatment approaches are needed in the stage IIB and IIC melanoma setting to help prevent disease recurrence, especially as distant metastases.

The DMFS data from KEYNOTE-716 reinforce the evidence for Keytruda as an adjuvant therapy for patients with completely resected stage IIB and IIC melanoma and show the potential of Keytruda to help reduce the risk of life-threatening distant recurrence and cancer spread for these patients.

What did the trial find with regard to recurrence-free survival?

Keytruda as adjuvant therapy continued to show a reduction in the risk of recurrence versus placebo (HR=0.64 [95% CI, 0.50-0.84]), at a median follow-up of 27.4 months.

Is there anything you’d like to add?

KEYNOTE-716 is the first trial of an anti-PD-1/L1 therapy to show a significant improvement in DMFS and RFS in the adjuvant setting for patients with stage IIB and IIC melanoma. Based on RFS data from KEYNOTE-716, Keytruda has been approved in the U.S. as adjuvant treatment for patients 12 years of age or older with completely resected stage IIB or IIC melanoma. On May 20, we achieved a positive CHMP recommendation for the same indication, and additional global regulatory filings are ongoing. 

Keytruda has already been established as an adjuvant treatment option across all sub-stages of completely resected stage III melanoma and is approved in over 90 countries based on the results from the EORTC1325/KEYNOTE-054 trial