Pembrolizumab ‘Standard Of Care’ for Ipilimumab-Refractory Melanoma

Pembrolizumab progression-free survival benefit demonstrated for patients with ipilimumab-refractory melanoma

medwireNews: The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab should be the new standard of care for patients with ipilimumab-refractory melanoma, KEYNOTE-002 investigators say.

Compared with 179 patients given their physician’s choice of cytotoxic chemotherapy, progression-free survival (PFS) was significantly better in 180 patients randomly assigned to receive a 2 mg/kg dose of pembrolizumab at 3-week intervals and 181 patients assigned to receive a 10 mg/kg dose, with hazard ratios of 0.57 and 0.50, respectively.

Six-month PFS was achieved by 34% and 38% of patients given the 2 mg/kg and 10 mg/kg pembrolizumab regimens, respectively, versus 16% of those given a chemotherapy regimen such as paclitaxel, carboplatin, dacarbazine or temozolomide.

All of the patients had experienced disease progression after prior ipilimumab and chemotherapy, including a MAPK pathway inhibitor in those with BRAFV600mutant-positive disease. Nevertheless, a treatment response was reported for 21% and 25% of the 2 mg/kg and 10 mg/kg pembrolizumab groups, respectively, versus 4% of those given chemotherapy.

Antoni Ribas, from the University of California, Los Angeles in the USA, and co-workers write in The Lancet Oncology that the results confirm that the two pembrolizumab doses have no significant difference in outcomes and are both superior to the current standard-of-care cytotoxic chemotherapy.

Acknowledging the positive results previously reported for the anti-PD-1 treatment nivolumab in ipilimumab-refractory and BRAFV600Wild-type melanoma, the team emphasises: “Our data are arguably of greater clinical relevance than are the data reported for nivolumab in this population because our study included patients with BRAFV600-mutant melanoma and we report progression-free survival and patient-reported outcomes data.”

Samantha Bowyer, from Rockingham General Hospital in Western Australia, and Paul Lorigan, from the University of Manchester in the UK, describe the study in an accompanying comment as “well designed and robustly carried out”.

In particular, they highlight the health-related quality of life data showing “the favourable tolerability of pembrolizumab” in a population of heavily pretreated patients with a poor prognosis.

Pembrolizumab-treated patients also had significantly fewer grade 3 or 4 treatment-related adverse events than those given chemotherapy (11–14 vs 26%) and were less likely to have treatment interruption (8 vs 18%).

“[F]or the future, first-line PD-1 inhibitors, or when approved, combination ipilimumab and nivolumab, should be a standard of care”, the commentators write.

“Given the potential toxicity and as yet unproven survival benefit of combination immunotherapy, a key task now is to test whether emerging biomarkers can help to better predict the most appropriate treatment, and establish whether non-responding patients can be converted into responders”, they add.

References

Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol 2015; Advance online publication 23 June. DOI: dx.doi.org/10.1016/S1470-2045(15)00083-2

Bowyer S, Lorigan P. The place of PD-1 inhibitors in melanoma management. Lancet Oncol 2015; Advance online publication 23 June. DOI: dx.doi.org/10.1016/S1470-2045(15)00094-7

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