Keytruda Shows Survival Benefits in Advanced Melanoma

Keytruda is a humanized monoclonal antibody that increases the ability of the immune system to detect and fight tumor cells.

The final overall survival (OS) data from the KEYNOTE-006 study and new findings from KEYNOTE-001 showed significant survival benefits with pembrolizumab (Keytruda) compared with ipilimumab in the first-line setting for advanced melanoma.

Keytruda is a humanized monoclonal antibody that increases the ability of the immune system to help detect and fight off tumor cells. Keytruda blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, resulting in the activation of T lymphocytes that could affect both tumor and healthy cells.

KEYNOTE-006 is a global, randomized, pivotal, open-label phase 3 study that looked to compare Keytruda versus ipilimumab in patients with unresectable stage 3 or 4 advanced melanoma who had no more than 1 previous systemic therapy.

The study included 834 patients randomized to receive either 10-mg/kg of Keytruda every 3 weeks, 10-mg/kg of Keytruda every 2 weeks, or 4 cycles of 3-mg/kg of ipilimumba every 3 weeks.

The co-primary endpoints included progression free survival (PFS) and OS, while the secondary endpoints were overall response rate (ORR), duration of response and safety, and an exploratory analysis for health related quality of life (QoL).

The results of KEYNOTE-006 found that long-term OS data showed a 55.1% and 55.3% of patients who were alive 2 years after starting the Keytruda treatment (10-mg/kg every 2 weeks and 3 weeks, respectively), compared with 43% who received ipilimumab (hazard ratio: 0.68 [95% CI, 0.53-0.87; p=0.0008] and hazard ratio: 0.68 [95% CI, 0.53-0.86; p=0.0008], respectively).

The median OS was not reached for Keytruda and was 16 months for ipilimumab.

After a longer follow-up, adverse events were consistent with previously reported safety data. Only 1 treatment-related death caused by sepsis occurred in the group taking Keytruda every 2 weeks.

In the phase 1b, multi-cohort, multicenter KEYNOTE-001 trial, Keytruda was evaluated in various advanced cancers, including advanced melanoma.

Participants in the melanoma cohorts were administered 2-mg/kg or 10-mg/kg of Keytruda every 3 weeks or 10-mg/kg of Keytruda every 2 weeks until unacceptable levels of toxicity were reached or disease progression occurred.

The study was assessed by a blinded independent review central facility that used the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to determine the primary efficacy outcome measure of ORR. The secondary outcome measures were PFS, OS, and duration of response.

There was a 10% complete response (CR) met in patients who responded to Keytruda. Of the 61 patients who stopped treatment once they had a CR, the response duration ranged from 17+ to 44+ months.

Only 2 patients who stopped treatment after achieving a CR experienced disease progression. The median survival was 24.4 months (95% CI, 20.2-29.0) and median duration was not reached.

For long-term survival, the trials revealed that 40% of patients survived 3 years after starting treatment with Keytruda (n=655) and had an ORR of 33%.

Adverse events remained the same after a longer follow-up, while immune-mediated treatment-related adverse events included hypothyroidism, pneumonitis, hyperthyroidism, colitis, uveitis, hepatitis, and nephritis.

“With longer-term follow-up from 2 studies, including a head-to-head trial demonstrating superior survival compared to another immunotherapy, we are continuing to see durability of response with Keytruda as monotherapy,” said Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development at Merck Research Laboratories. “These results add to the growing body of data supporting the use of Keytruda as first-line treatment in advanced melanoma, and serve as an important reminder for what we are aiming to achieve through our immuno-oncology development program — enhanced survival for people with cancer.”

Data from the KEYNOTE-006 and KEYNOTE-001 trials will be presented in June at the Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.