Nivolumab, ipilimumab duo effective in poor prognosis advanced melanoma patients

Oct 5 2015

By Shreeya Nanda, Senior medwireNews Reporter

Subgroups of advanced melanoma patients with a poor prognosis derive a progression-free survival (PFS) benefit from the combination of nivolumab and ipilimumab, according to research presented at the European Cancer Congress in Vienna, Austria.

Presenting author James Larkin, from the Royal Marsden Hospital in London, UK, said in a press release that “[w]e believe that the data will give confidence to patients and their healthcare providers that the combination of nivolumab and ipilimumab will be effective regardless of advanced age, the presence of a BRAF mutation, or poor prognostic factors.”

In the previously reported results for the overall population of the CheckMate 067 phase III trial, median PFS was 11.5 months for the 314 previously untreated patients who received the programmed death-1 inhibitor nivolumab plus ipilimumab, which blocks cytotoxic T-lymphocyte-associated protein 4, followed by nivolumab alone. This was significantly higher than the median PFS of 6.9 months for the 316 participants given nivolumab plus placebo and the 2.9 months for the 315 patients treated with ipilimumab plus placebo.

And the latest subgroup analysis shows that the advantage afforded by the combination treatment was maintained regardless of patient age, serum lactate dehydrogenase levels, extent of metastatic disease and BRAF mutation status.

Among patients aged 75 years or older, median PFS was higher for the nivolumab plus ipilimumab and nivolumab alone groups than for the ipilimumab alone group (not reached and 5.3 vs 4.0 months, respectively), with corresponding hazard ratios (HRs) of 0.51 and 0.84. And Larkin pointed out in his presentation that the combination was “numerically superior” to nivolumab alone.

However, he highlighted that in the 65–74 years age group, the combination and single-agent nivolumab groups had similar HRs when compared with the ipilimumab alone group, at 0.39 and 0.36, respectively, but added that “caution is necessary with interpretation”.

Patients with stage M1c disease also benefited from dual therapy, achieving a median PFS of 8.5 months compared with 5.4 and 2.8 months for the nivolumab and ipilimumab monotherapy arms, respectively.

And similar improvements with nivolumab plus ipilimumab were also seen across the other predefined subgroups, reported Larkin et al.

The incidence of grade 3 or 4 treatment-related adverse events in the subgroups was also comparable to the rates observed in the total population. For instance, among patients aged 75 years and above, grade 3 or 4 toxicities occurred in 48% of combination-treated patients, 21% of nivolumab-treated patients and 36% of ipilimumab-treated patients. These rates were similar to the corresponding rates in the overall study population, at 55%, 16% and 27%, respectively.

Larkin added that the rates of resolution of adverse events in patients treated with immune modulators was generally high – between 90% and 100% for most organ categories – except for endocrine toxicities, which typically did not resolve and required replacement therapy.

He concluded that, overall, nivolumab and ipilimumab provided “a favourable benefit–risk profile in treatment-naïve advanced melanoma patients, including those with poor prognostic factors”.

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