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Pembrolizumab significantly improved overall survival (OS) versus ipilimumab for unresectable advanced melanoma in KEYNOTE-006 (NCT01866319); 10-year follow-up data are presented. Patients with unresectable stage III or IV melanoma were randomly assigned (1:1:1) to pembrolizumab 10 mg/kg i.v. every 2 weeks or every 3 weeks for ≤2 years (pooled), or ipilimumab 3 mg/kg i.v. every 3 weeks for four cycles. After KEYNOTE-006, patients could transition to KEYNOTE-587 (NCT03486873) for long-term follow-up. Eligible patients could receive second-course pembrolizumab. The primary endpoint was OS; modified progression-free survival (PFS; censored at date last known alive), modified PFS on second-course pembrolizumab, and melanoma-specific survival were exploratory. Of 834 patients randomly assigned in KEYNOTE-006 (pembrolizumab, n = 556; ipilimumab, n = 278), 333 (39.9%) were eligible for KEYNOTE-587; 211/333 patients (25.3%) transitioned to KEYNOTE-587 (pembrolizumab, n = 159; ipilimumab, n = 52) and 122 (14.6%) did not. For patients who transitioned to KEYNOTE-587 (n = 211), median time from randomization in KEYNOTE-006 to data cut-off for KEYNOTE-587 (1 May 2024) was 123.7 months (range, 122.0-127.3 months). Median OS was 32.7 months [95% confidence interval (CI) 24.5-41.6 months] for pembrolizumab and 15.9 months (95% CI 13.3-22.0 months) for ipilimumab [hazard ratio (HR), 0.71 (95% CI 0.60-0.85)]; 10-year OS was 34.0% and 23.6%, respectively. Among patients who completed ≥94 weeks of pembrolizumab, median OS from week 94 was not reached (NR; 95% CI NR-NR); 8-year OS rate was 80.8%. Median modified PFS was 9.4 months (95% CI 6.7-11.6 months) for pembrolizumab and 3.8 months (2.9-4.3 months) for ipilimumab [HR, 0.64 (95% CI 0.54-0.75)]. Among patients who received second-course pembrolizumab, median modified PFS from start of second course was 51.8 months (95% CI 11.0 months-NR); 6-year modified PFS was 49.2%. Median melanoma-specific survival was 51.9 months (95% CI 30.0-114.7 months) for pembrolizumab and 17.2 months (13.9-25.9 months) for ipilimumab [HR, 0.66 (95% CI 0.55-0.81)]. These results confirm that pembrolizumab provides long-term survival benefits in advanced melanoma, supporting it as a standard of care in this setting. • The 10-year follow-up of KEYNOTE-006 confirms that pembrolizumab provides long-term survival benefit in advanced melanoma. • The 10-year OS rate was 34.0% in the combined pembrolizumab arm versus 23.6% in the ipilimumab arm. • OS favored pembrolizumab versus ipilimumab across subgroups, including in patients with poor prognostic features. • Median MSS was also improved with pembrolizumab versus ipilimumab [51.9 versus 17.2 months; HR, 0.66 (95% CI 0.55-0.81)]. • For patients who received second-course pembrolizumab (n = 16), the 6-year modified PFS from start of second course was 49.2%. [ABSTRACT FROM AUTHOR]

Background Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established. Patients and Methods This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N  =   167) or nivolumab (N  =   18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia. Results Median time on treatment was 12 months (range 0.7–43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18 months (range 0.7–48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12 months (range 2–23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response. Conclusions In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6 months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients. Clinical trial registration NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3) [ABSTRACT FROM AUTHOR]