2024 ESMO West: Long-Term Melanoma Updates with Dr Theresa Medina
Presenter:
Theresa Medina, MD, University of Colorado
Conference:
2024 ESMO West
At the 2024 ESMO West Conference, Dr Theresa Medina from University of Colorado, presented updates from two key studies on long-term melanoma outcomes. Findings reported at this year’s European Society for Medical Oncology (ESMO) Congress from the CheckMate 067 and KEYNOTE-006/KEYNOTE-587 trials provide valuable insights into the sustained impact of immunotherapies in advanced melanoma and highlight how these therapies are reshaping survival outcomes for patients.
CheckMate 067: 10-Year Survival Outcomes with Nivolumab and Ipilimumab
The CheckMate 067 trial represents a milestone in melanoma research, with a decade of follow-up demonstrating the profound impact of dual immune checkpoint blockade. This phase III trial randomized patients with advanced melanoma to receive one of three treatments: a combination of nivolumab (an anti-PD-1 immunotherapy) and ipilimumab (an anti-CTLA-4 immunotherapy), nivolumab monotherapy, or ipilimumab monotherapy. Patients continued therapy as long as there was clinical benefit and manageable toxicity.
Dr. Medina noted how the combination of nivolumab and ipilimumab yielded remarkable outcomes. At the 10-year mark, patients receiving the combination therapy had a median overall survival (OS) of 72 months, as compared to 37 months for nivolumab monotherapy and only 10 months for ipilimumab monotherapy. In addition, melanoma-specific survival (MSS) exceeded 10 years (median not reached) for combination therapy, with survival rates of 55% at 7.5 years. These rates were significantly higher than the MSS of 49 months and 22 months observed with the nivolumab and ipilimumab monotherapies, respectively.
Progression-free survival (PFS) at three years also emerged as a powerful predictor of long-term outcomes. Patients who achieved PFS at three years in the nivolumab-containing arms demonstrated 10-year MSS rates exceeding 96%. In addition, the depth of tumor response correlated strongly with survival. For patients with an 80% or greater reduction in tumor burden, the MSS at 10 years was over 80%.
Importantly, survival outcomes were not negatively impacted by the occurrence of grade 3–4 treatment-related adverse events (TRAEs). Dr. Medina noted that fewer patients in the combination therapy arm required subsequent systemic therapy, highlighting its durable efficacy. Dr. Medina emphasized that CheckMate 067 sets a new benchmark for long-term survival in advanced melanoma and redefines expectations for the role of immune checkpoint inhibitors.
KEYNOTE-006/KEYNOTE-587: Long-Term Benefits of Pembrolizumab
KEYNOTE-006 initially compared pembrolizumab, an anti-PD-1 antibody, to ipilimumab in patients with advanced melanoma. The long-term follow-up of these patients was conducted under KEYNOTE-587. Patients who achieved clinical benefit with pembrolizumab during KEYNOTE-006 could receive a second course of the drug if they progressed after completing their initial therapy.
With now a decade of follow-up, pembrolizumab demonstrated clear superiority over ipilimumab. The 10-year OS rate was 34% for pembrolizumab versus 22.8% for ipilimumab. Progression-free survival (PFS) rates were also significantly better for pembrolizumab, at 22% compared to 12.8% for ipilimumab. Melanoma-specific survival was similarly improved, with 45.2% of pembrolizumab-treated patients alive at 10 years compared to 31.3% in the ipilimumab group.
Also particularly impressive was the durable response observed in patients who completed two years of pembrolizumab therapy. At eight years of follow-up, OS and PFS rates were 80.8% and 84.8%, respectively, among this cohort. Additionally, re-treatment with pembrolizumab proved effective, with nine out of 16 re-treated patients achieving partial or complete responses.
Dr. Medina highlighted the robust benefit of pembrolizumab across diverse patient subgroups, including those with high tumor burden, those with elevated lactate dehydrogenase (a high risk feature), and those with brain (CNS) metastases. She noted that pembrolizumab has become a standard of care in advanced melanoma due to its favorable efficacy and tolerability profile.
Summary
The findings from CheckMate 067 and KEYNOTE-006/587 reinforce the transformative potential of immune checkpoint inhibitors in advanced melanoma. With durable survival benefits extending beyond a decade for a subset of patients, these therapies are reshaping the landscape of melanoma care. Both studies, however, also highlight ongoing challenges, as not all patients achieve long-term remission. Future research is needed to identify biomarkers that predict response and to develop strategies for improving outcomes in non-responders. These trials also exemplify how immunotherapy has shifted melanoma treatment paradigms, offering hope for long-term survival and, in some cases, potential cure. Dr. Medina concluded her presentation by emphasizing the importance of continuing innovation to address the unmet needs of melanoma patients.
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Speaker Disclosure Information: Dr Medina reported the following disclosures for this presentation:Institutional Research Funding: BMS, Merck, Iovance, Genentech, Pfizer, Moderna, Ultimovacs, Regeneron, Replimune, Trisalus, DayOne, Anaveon