Combinations provide sustained benefit

Immune-checkpoint inhibitors (ICIs) have dramatically altered the prognosis of patients with advanced-stage melanoma. Now, 5-year follow-up data from CheckMate 067 confirm the long-term survival of patients receiving these therapies.

A total of 945 patients were randomized (1:1:1) to receive either nivolumab plus 4 doses of ipilimumab, followed by nivolumab monotherapy; nivolumab monotherapy; or ipilimumab monotherapy until disease progression, unacceptable toxicities, or withdrawal of consent. Progression-free survival (PFS) and overall survival (OS) were the primary end points of this trial.

At a follow-up duration of ≥60 months, median OS durations were not reached, 36.9 and 19.9 months in the nivolumab plus ipilimumab, nivolumab, and ipilimumab groups, respectively. Just over half (52%) of patients receiving nivolumab plus ipilimumab were alive at 5 years of follow-up monitoring.

A total of 36 patients were continuing to receive treatment at the current data-cut-off. Assessments of treatment-free interval, excluding patients who discontinued follow-up or died prior to subsequent therapy, revealed a median duration of 18.1, 1.8 and 1.9 months in patients in the nivolumab plus ipilimumab, nivolumab and ipilimumab monotherapy groups, respectively.

No notable new adverse events emerged at this data cut-off: 58% of patients receiving nivolumab plus ipilimumab had grade 3–4 adverse events, compared with 23% and 28% in the nivolumab and ipilimumab groups, respectively. The majority of adverse events had resolved at the time of data cut-off, with the exception of endocrine events, including 6 patients with grade 3–4 diabetes, and 68 patients with thyroid disorders of any grade.

These data confirm that the benefits of ICIs can be sustained for >5 years in patients with advanced-stage melanoma who respond to these agents and that the majority of adverse events are reversible. However, irreversible adverse events can occur and will likely require lifelong management.


Original article

  1. Larkin, J. et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N. Engl. J. Med. (2019)

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Correspondence to Peter Sidaway.

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Sidaway, P. Combinations provide sustained benefit. Nat Rev Clin Oncol 16, 723 (2019).

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