Proffered paper on skin cancer

While ESMO did not feature any practice-changing presentations in the field of melanoma, it did provide interesting, long-term updates of pivotal clinical trials in addition to important insights from real-world data. In this video, Prof Dr Jean-Francois Baurain (Cliniques Universitaires St.-Luc, Brussels) talks us through the key take-aways from these different presentations.

First of all, 10-year follow up data were presented for two pivotal clinical trials that established immune checkpoint inhibition (ICI) as the standard of care first line treatment for patients with advanced melanoma. CheckMate 067 convincingly demonstrated an overall survival (OS) benefit for the combination of ipilimumab (ipi) and nivolumab (nivo) over nivo or ipi alone in the first line treatment of patients with advanced melanoma. At the 10-year landmark, 43% of patients treated with ipi-nivo were still alive as compared to 37% with nivo alone and only 19% with ipi monotherapy. The corresponding median OS with the three regimens were 71.9, 36.9 and 19.9 months, respectively.1 Ten-year follow-up data were also presented for the phase III KEYNOTE-006 study comparing pembrolizumab (pembro) to ipi as first line treatment for advanced melanoma. In this trial, the median OS was reported at 32.7 months for pembro, which was twice as long as the 15.7-month median OS seen with ipi. Ten-year OS rates were 34% and 23.6% with pembro and ipi, respectively.2 Interestingly, in both studies the median OS proved to be shorter than the median melanoma-specific survival. As such, these findings indicate that patients were more likely to die from other causes than from melanoma.

Following the success of ICI in metastatic melanoma, several studies evaluated the use of these agents in the neoadjuvant and adjuvant treatment of patients with resectable melanoma. During ESMO 2024, Georgina Long presented the long-term results of a pooled analysis of 818 patients with resectable stage ≥IIIB melanoma who were treated with neoadjuvant therapy.3 This analysis concluded that neoadjuvant therapy should be standard of care for these patients, with the highest rate of major pathological response (MPR), relapse-free survival (RFS) and event-free survival (EFS) in patients who received combination ICI in the neoadjuvant setting (3-year EFS rate 78% mounting to 94% in patients with a MPR [~60%]). Neoadjuvant BRAF/MEK inhibition was not as effective as ICI and did not provide a benefit over the use of this treatment modality in the adjuvant setting.3

Based on the convincing RFS benefit demonstrated in different clinical trials, adjuvant therapy with anti-PD-1 therapy or BRAF/MEK inhibitors have become standard of care for patients with stage III melanoma. To assess the impact of this treatment shift, Swedish researchers used real-world data to compare the OS of node-positive, stage III melanoma patients in the pre and post adjuvant therapy era. Surprisingly, the 3-year OS rates, in the pre and post cohorts were almost identical at 80.1% and 80.9%, respectively (HR[95%CI]: 0.92[0.71-1.18]).4 The reason for the lack of an OS effect is unclear, but probably the follow-up in this study is still too short to see a difference.

A final abstract selected by Prof Baurain looked at the outcome of melanoma patients with minimal sentinel node (SN) burden who did not undergo a complete lymph node dissection (CLND). For this study, minimal SN burden was defined as having subcapsular lesions with a maximum diameter of 0.4 mm or lesions with a maximum diameter of 0.1 mm in non-subcapsular locations. Among the 149 pT2-pT3 patients who opted for observation instead of CLND, the 5-year cumulative incidence of distant metastasis was reported at 15%. At 5 years, only 8.2% of these pT2-pT3 observation patients had died due to melanoma.5 The survival outcomes for melanoma patients with a minimal SN burden in this analysis fuel the discussion on the added value of adjuvant therapy in this setting.