CheckMate-067: 10-year survival outcome

During ESMO 2024, 10-year follow data were presented of the pivotal phase III CheckMate 067 trial. With a 10-year overall survival (OS) rate of 43% with the combination of nivolumab and ipilimumab and 37% for nivolumab alone, this trial once again underscores how immune checkpoint inhibitors have transformed the long-term prognosis for patients with advanced melanoma. In this video Prof Dr Bart Neyns and Prof Dr John Haanen, medical oncologists, respectively at the University Hospital Brussels and at the National Cancer Institute in Amsterdam, share their reflections on these long-term data.

Both physicians remember the pre-immunotherapy era in melanoma when almost none of the patients presenting with unresectable disease survived beyond 5 years. The long-term data from CheckMate 067 now show a spectacular 10-year OS of about 40%. Furthermore, patients who are disease free 5 years after the start of their treatment have a very low risk to die from their melanoma at all. 

Prof Haanen reminds us that CheckMate 067 was initially developed to compare the efficacy of nivolumab with or without ipilimumab to that of ipilimumab alone. However, even though this study is not powered to do so, its results are often used to compare nivolumab monotherapy to the nivolumab-ipilimumab combination. In clinical practice the choice between these two treatment options should balance the differences in efficacy and toxicity and take into consideration the preference of the patient. In any case, Prof Neyns indicates that he is not uncomfortable with starting nivolumab as monotherapy in patients who prefer this option. One exception to this consists of patients with baseline central nervous system involvement for whom the nivolumab-ipilimumab combination seems to be the better option. 

Finally, one must acknowledge that the unresectable melanoma patients who are seen in the current clinical practice differ from the patient population that entered CheckMate 067. In fact, with the introduction of immune checkpoint inhibition in the (neo)adjuvant setting, many patients presenting with unresectable disease have already been exposed to an anti-PD-1 agent. To what extent this prior exposure impacts the effectiveness of anti-PD-1 therapy in the advanced setting is not yet clear. For patients who prove to be refractory to anti-PD1 therapy several new therapies are emerging, including tumour infiltrating lymphocyte (TIL) therapy, bispecific T-cell engagers and intralesional treatments. While these treatment modalities have shown significant biological activity, this does not yet translate into a spectacular improvement in patient outcomes.