medwireNews: An updated analysis of the CheckMate 067 trial shows continued survival benefits at 4 years with nivolumab plus ipilimumab or nivolumab monotherapy versus ipilimumab alone in patients with previously untreated advanced melanoma.
The study findings are published in The Lancet Oncology and were also presented at the ESMO 2018 Congress in Munich, Germany.
For the first time, the CheckMate 067 researchers also looked at outcomes in patients who discontinued the combination therapy because of treatment-related adverse events, and they found that survival in this group was similar to that among patients who did not discontinue due to adverse events.
Commenting on the findings, Mark Middleton, from the University of Oxford in the UK, describes this result as “very reassuring” particularly because “[t]hree times as many patients discontinued combination therapy because of drug toxicity as those who stopped nivolumab monotherapy for this reason.”
For the double-blind study, patients with previously untreated, unresectable, stage III or IV melanoma were randomly assigned to receive intravenous nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks (n=314), or to receive nivolumab 3 mg/kg every 2 weeks alongside placebo (n=316) or ipilimumab 3 mg/kg every 3 weeks for four doses plus placebo (n=315).
After a minimum follow-up of 48 months from final patient enrolment, median overall survival (OS) had not been reached for the patients who received nivolumab plus ipilimumab, and was 36.9 months and 19.9 months for those in the nivolumab and ipilimumab groups, respectively. The corresponding 4-year OS rates were 53%, 46%, and 30%.
Median progression-free survival (PFS) was 11.5 months in the combination group, 6.9 months in the nivolumab group, and 2.9 months in the ipilimumab group, with 4-year PFS rates at 37%, 31%, and 9%, respectively.
Compared with ipilimumab, combination therapy was associated with a significant 58% reduced risk for disease progression or death and a significant 46% reduced risk for death alone. For nivolumab alone versus ipilimumab alone the corresponding risk reductions were a significant 47% and 35%.
Furthermore, F Stephen Hodi (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and co-investigators say that “[a]lthough the CheckMate 067 study was not designed to compare the two nivolumab-containing groups, descriptive analyses suggest that improved 4-year survival might be achieved with nivolumab plus ipilimumab than with nivolumab alone.”
Post-hoc analysis among patients in the combination therapy group showed that PFS and OS were 11.1 months and not reached, respectively, in the 74 patients who discontinued therapy because of treatment-related adverse events during the induction phase, compared with 8.6 and 37.1 months in 187 patients who did not discontinue due to such events.
In his commentary, Middleton says that “Hodi and colleagues have provided further evidence that the combination of ipilimumab and nivolumab offers better outcomes than either agent alone for patients with metastatic disease who are fit enough to undergo treatment.”
However, he is critical of the fact that the study did not include a formal comparison of the two nivolumab groups and provided no information about quality of life once the patients were off treatment.
Therefore, even though Hodi and team reported that patients in the combination group had a longer median treatment-free interval (15.4 months) after stopping therapy for any reason than those in the nivolumab (1.7 months) and ipilimumab (1.9 months) groups, Middleton suggests that the lack data on patient-experience makes it “difficult to assess the value” of this prolonged period without treatment.
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group