One of the flagship clinical trials of checkpoint inhibitors in metastatic melanoma, which established the combination of nivolumab and ipilimumab as a standard of care, has also provided the first report of melanoma-specific survival (MSS).

A post hoc analysis of CheckMate-067 has reported the median MSS was not reached with combination treatment, compared to 58.7 months with nivolumab and 21.9 months with ipilimumab alone.

In the three groups, the 6.5-year MSS rates were 56%, 48%, and 27%, respectively.

The study, published in the Journal of Clinical Oncology, said MSS was an important outcome measure “given the increasing competing risk of death from other causes that the durable control of melanoma with checkpoint inhibitors affords.”

The traditional measure of PFS was 11.5 months in the combination group, 6.9 months in the nivolumab group, and 2.9 months in the ipilimumab group. As well, the median OS was 72.1 months in the combination group, 36.9 months in the nivolumab group, and 19.9 months in the ipilimumab group.

The treatment-free interval in the combination group was 27.6 months compared to 2.3 months with nivolumab and 1.9 months with ipilimumab.

“Among patients who were alive at the data cutoff, 77%, 69%, and 43% in the three groups were treatment-free, respectively,” the study said.

No new or unexpected safety signals were reported.

An editorial in the journal said the impact of CheckMate-067 extends well beyond melanoma.

“Phase III trials are typically designed to compare response rates, progression-free survival, and OS, but it is noteworthy to mention that of CheckMate-067 patients who received ipilimumab plus nivolumab and were alive at the data cutoff, 77% are off therapy and never received subsequent therapy.”

It said treatment-free survival was increasingly recognised as a valuable outcome measure.

“Prolonged TFS translates into less toxicity to the patient from a physical, psychological, and financial perspective.

“In CheckMate-067, patients receiving ipilimumab plus nivolumab were treated for a median of only 3.6 months, probably partially attributable to drug discontinuation after the development of high-grade AEs. However, the majority of patients treated with the combination came off treatment and remained off treatment.”

“For other stage IV diagnoses in solid tumour oncology, TFS has been largely unattainable, and for melanoma, it has been attainable only for interleukin-2 and adoptive cell therapy.”

The editorial said future trials should incorporate outcomes such as TFS, and up-front versus ongoing costs, to determine the value of the high-cost immune checkpoint inhibitors.

The study was supported by Bristol Myers Squibb.