'Encouraging' Data on Ipilimumab Plus Anti-PD-1 in Metastatic Melanoma

By Reuters Staff

June 01, 2021

NEW YORK (Reuters Health) - For patients with advanced melanoma resistant to anti-PD-(L)1 monotherapy, combining the CTLA-4 inhibitor ipilimumab with an anti-PD-1 agent "should be favored" over ipilimumab alone as second-line immunotherapy, researchers say.

Anti-PD-1 therapy induces long-term disease control in about 30% of patients with metastatic melanoma. However, two-thirds of patients are resistant to anti-PD-1 therapy and will require further treatment, Dr. Ines Pires da Silva of the University of Sydney, Australia, and colleagues note in The Lancet Oncology.

The researchers reviewed the outcomes with ipilimumab alone or with the anti-PD-1 drugs pembrolizumab or nivolumab (combination immune-checkpoint inhibitor immunotherapy) in 355 patients with metastatic melanoma resistant to anti-PD-(L)1 therapy.

Patients who received combination therapy were younger than those who received ipilimumab monotherapy (median age 61 vs. 67 years), had a better Eastern Cooperative Oncology Group (ECOG) performance status and were more likely to have BRAF or NRAS mutant melanoma.

There were no differences in other key prognostic factors, such as elevated lactate dehydrogenase and presence of liver or brain metastases; however, patients with more than three organs involved were more likely to receive ipilimumab monotherapy.

At a median of 22 months, the objective response rate was higher with combination therapy than ipilimumab monotherapy (31% vs. 13%; P<0.0001) and median overall survival was longer (20.4 months vs. 8.8 months; hazard ratio 0.50; 95% CI: 0.38 to 0.66; P<0.0001).

Progression-free survival was also longer with ipilimumab plus anti-PD-1 therapy (median 3.0 months vs. 2.6 months; HR, 0.69; 95% CI, 0.55 to 0.87;s P=0.0019).

"Surprisingly," say the authors of a linked comment, similar proportions of patients reported grade-3 to -5 adverse events in both groups (31% in the combination group and 33% in the monotherapy group).

The most common grade-3 to -5 adverse events were diarrhea or colitis (12% in the ipilimumab plus anti-PD-1 group and 20% in the ipilimumab group) and increased alanine aminotransferase or aspartate aminotransferase (12% and 9%).

This study provides "encouraging data in support of this treatment combination," Dr. Annie Wong and Dr. David Gyorki of Peter MacCallum Cancer Center, in Melbourne, Australia, write in their comment.

"In the absence of randomized and prospective trial data, this retrospective study provides the strongest evidence so far to support the use of combination ipilimumab plus anti-PD-1 in patients whose melanoma has progressed, and who are resistant to anti-PD-(L)1 monotherapy," they conclude.

The study had no specific funding. Several authors disclosed financial relationships with the pharmaceutical industry.

SOURCE: https://bit.ly/2S95tcM and https://bit.ly/33Wrii5 Lancet Oncology, online May 11, 2021.