14-05-2025
OS Benefit of Melanoma Adjuvant Therapy Unclear
This transcript has been edited for clarity.
Welcome back, everybody. My name is Teresa Amaral, and it's really a pleasure to have you back for this Medscape melanoma series. We are going to continue with our second part on what's next in terms of immunotherapy in the adjuvant setting for patients diagnosed with melanoma.
In the first episode, we discussed the current status of adjuvant therapy reimbursement and utilization — who are the patients that are candidates to receive adjuvant therapy but not neoadjuvant therapy, why we have these therapies approved, and what was the benefit of these therapies. We mentioned that the benefit was in terms of relapse-free survival and distant metastasis-free survival.
Today we are going to discuss whether there is an overall survival benefit, which is probably the question that you are asking yourself.
Indeed, there is no evidence in terms of overall survival benefit coming from phase 3 trials evaluating immunotherapy in the adjuvant setting. There might be a benefit that is lost in terms of adjuvant benefit from these therapies because we have therapies that are quite effective in stage IV, or in advanced stage for patients diagnosed with melanoma, that are able to 'rescue' the patients who did not benefit from this adjuvant therapy as we expected.
We have been waiting for the final results from KEYNOTE-054, a trial that evaluated the use of adjuvant pembrolizumab in stage III, that was specifically designed to address the question of whether there was an overall survival benefit in this setting by using this therapy.
Initially, the results for the overall survival benefit were planned for 2023, but they have been delayed to 2027, based on the information that is available on the EMA site, which means that until that time point, we most likely will not be able to determine whether there is an overall survival benefit from this therapy used in the adjuvant setting.
There is also another trial, CheckMate 238, that evaluated the use of adjuvant ipilimumab vs nivolumab. We saw after 7 years of follow-up that there was no benefit in terms of overall survival, despite seeing a benefit in terms of relapse-free survival and distant metastasis-free survival, w hich questions whether there is really a link in terms of this benefit that we see, in terms of relapse and overall survival in the long run.
Two other trials also evaluated adjuvant therapy and showed that there was no benefit in terms of overall survival in this setting. The first trial is the SWOG trial, S1404, which evaluated pembrolizumab vs standard of care, which was at the time either interferon or other trial is the IMMUNED trial, which was evaluating adjuvant therapy in resected stage IV.
In both trials we saw that there was a benefit, again, in terms of relapse-free survival, but we didn't see any overall survival benefit. This raises the question of whether we will ever see this overall survival benefit in patients treated with adjuvant immunotherapy.
There is also evidence from real-world data, specifically from a Swedish registry study, that showed that the patients treated with adjuvant therapy after this therapy becoming available didn't have a benefit in terms of overall survival compared with the patients who were diagnosed in the era pre-adjuvant therapy approval, which again raises the question of whether we will see this overall survival benefit at all.
We also have real-world data from an analysis in the US that looked into patients treated in clinical practice and receiving adjuvant therapy, where we did see a benefit in terms of overall survival. Again, with all of the conflicting data, it is difficult to understand if this overall survival r eally exists.
Finally, we need to consider that the absence or presence of overall survival benefit might be conditioned by the access to therapies that could or could not be available when the patients have a recurrence in an advanced setting after receiving adjuvant therapy.
You may question, what is the problem of not having overall survival benefit?Why is this important and why are we discussing this? This will be the topic of our next episode.
