Alexander M. M. Eggermont, MD, PhD, professor of oncology, University of Paris-Sud, professor of oncological surgery, chair, International Research Network on Cancer, Erasmus University of Rotterdam, Joseph Maisin Honorary Chair of Oncological Surgery, Louvain Catholic University, discusses the rationale for the 

evaluating adjuvant pembrolizumab (Keytruda) versus placebo, in advanced melanoma.

​Early research showed response rates of about 45% to 50%, as well as 5-year overall survival rates of about 45%, with pembrolizumab (Keytruda) in treatment-naïve patients ​with advanced melanoma, says Eggermont.

As such, the phase 3 KEYNOTE-054 trial ​​further evaluated pembrolizumab in ​the adjuvant setting versus placebo in patients with resected, high-risk, stage III melanoma, says Eggermont.

The trial randomized 1019 ​lymph node–positive patients to pembrolizumab at a flat dose of 200 mg or placebo every 3 weeks for 1 year or until recurrence or unacceptable toxicity. 

The primary end point ​of the study was recurrence-free survival; secondary end points included distant metastasis-free survival and overall survival, concludes Eggermont.

Videos

Alexander M. M. Eggermont, MD, PhD, discusses the rationale for the phase 3 EORTC 1325/KEYNOTE-054 trial, ​evaluating adjuvant pembrolizumab versus placebo, in advanced melanoma.

Dr. Eggermont on the Rationale for Evaluating Adjuvant Pembrolizumab in Advanced Melanoma

Alexander M. M. Eggermont, MD, PhD, professor of oncology, University of Paris-Sud, professor of oncological surgery, chair, International Research Network on Cancer, Erasmus University of Rotterdam, Joseph Maisin Honorary Chair of Oncological Surgery, Louvain Catholic University, discusses responses to adjuvant pembrolizumab (Keytruda) in patients with different subtypes of stage III melanoma.

Within stage III melanoma, there is stage IIIA disease, which encompasses microscopic lymph node involvement, IIIB disease, and IIIC disease, says Eggermont.

In updated findings from the phase 3 EORTC 1325-MG/KEYNOTE-054 trial, pembrolizumab (Keytruda) showed consistently better rates of recurrence-free survival (RFS) compared with placebo across stage III subtypes, explains Eggermont. Moreover, at a 3-year median follow-up, the hazard ratios with pembrolizumab were 0.50 in stage IIIA disease, 0.56 in IIIB disease, and 0.57 in IIIC disease. Additionally, RFS rates were 81.2%, 65.7%, and 54.3%, respectively.

These findings add to the discussion of whether pembrolizumab should be considered for patients with stage IIIA disease, concludes Eggermont.

Alexander M. M. Eggermont, MD, PhD, discusses responses to adjuvant pembrolizumab in patients with different subtypes of stage III melanoma. 

Dr. Eggermont on Responses to Adjuvant Pembrolizumab in Stage III Melanoma Subtypes

Alexander M. M. Eggermont, MD, PhD, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France, discusses the impact of pembrolizumab (Keytruda) in the treatment of patients with relapsed melanoma.

Based on the significant impact of overall survival (OS) that has been seen in clinical trials with pembrolizumab as well as researchers’ prior discovery of the PD-1 antibody’s impact on metastases-free survival, this agent should be considered the standard treatment in the relapsed setting, Eggermont says. In the KEYNOTE-054 study, 27.5% of patients treated with placebo developed distant metastases compared with 16% on the pembrolizumab arms. Eggermont says that when such efficacy is seen in a primary endpoint like metastases-free survival, there typically is a significant improvement in OS.

If a drug is active enough to bring all of these benefits at the time of administration, Eggermont says, it is reasonable to expect an improvement in OS. These findings from the KEYNOTE-054 study will be available in 2.5 years.

Alexander M. M. Eggermont, MD, PhD, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France, discusses the impact of pembrolizumab in melanoma.

Dr. Eggermont Discusses Impact of Pembrolizumab in Melanoma

Alexander M. M. Eggermont, MD, PhD, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France, discusses the impact of adjuvant anti—PD-L1 agents on the treatment landscape of melanoma.

In a study presented at the 2018 AACR Annual Meeting, adjuvant pembrolizumab (Keytruda) reduced the risk of recurrence or death by 43% in patients with resected, high-risk stage III melanoma. The EORTC 1325-MG/KEYNOTE-054 trial randomized patients to 200 mg of pembrolizumab (n = 514) or placebo (n = 505) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxicity.

These results, paired with the FDA approval of nivolumab (Opdivo) as an adjuvant treatment for patients with completely resected melanoma with lymph node involvement or metastatic disease, has completely changed this setting, says Eggermont. The previously favored ipilimumab (Yervoy) is likely to be replaced with 2 efficacious PD-1 inhibitors, Eggermont concludes.

Alexander M. M. Eggermont, MD, PhD, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France, discusses the impact of adjuvant anti–PD-L1 agents on the treatment landscape of melanoma.
 

Alexander M. M. Eggermont, MD, PhD

Articles

Dr. Eggermont on the Rationale for Evaluating Adjuvant Pembrolizumab in Advanced Melanoma

Dr. Eggermont on Responses to Adjuvant Pembrolizumab in Stage III Melanoma Subtypes

Dr. Eggermont Discusses Impact of Pembrolizumab in Melanoma

Dr. Eggermont on the Impact of Adjuvant Anti-PD-L1 Agents in Melanoma