Opdivo, Opdualag Still Benefits Patients With Melanoma at 2 Years

Article

After two years of follow-up, patients with advanced melanoma treated with Opdivo and Opdualag continued to obtain a survival benefit compared with Opdivo alone.

Patients with previously untreated, unresectable or metastatic melanoma continued to derive a benefit after two years from treatment with Opdivo (nivolumab) plus Opdualag (relatlimab) compared with Opdivo alone, according to recent trial data.

These findings were presented by Dr. Hussein A. Tawbi at the 2023 ASCO Annual Meeting.

The phase 3 trial RELATIVITY-047 had shown an improvement in (progression-free survival) that was statistically significant and hit the primary end point even at a median follow-up of only 13.2 months.

Findings from the RELATIVITY-047 trial showed an improvement in progression-free survival.

The updated progression-free survival analysis data favored the combination of Opdivo plus Opdualag. In particular, patients receiving Opdivo plus Opdualag (355 patients) achieved a median progression-free survival (the time during and after treatment when a patient with cancer is alive without disease worsening) of 10.2 months versus 4.6 months for those given Opdivo monotherapy (359 patients). Median overall survival (the time when a patient with cancer is still alive) was not reached in the doublet arm and was 33.2 months in the monotherapy arm.

“The phase 3 trial RELATIVITY-047 had shown an improvement in (progression-free survival) that was statistically significant and hit the primary end point even at a median follow-up of only 13.2 months. This has resulted in the FDA approval of this combination in the first line for patients with metastatic melanoma,” said Tawbi, who is the director of personalized cancer therapy and deputy chair in the department of melanoma medical oncology at The University of Texas MD Anderson Cancer Center in Houston.

Efficacy

For patients receiving Opdivo plus Opdualag, the 12-, 24- and 36-month progression-free survival rates were 48%, 38% and 31%, respectively. Overall survival rates were 77%, 62% and 54%, at these time points, respectively, with a 48-month overall survival rate of 52%.

For those given Opdivo alone, the 12-, 24-, and 36-month progression-free survival rates were 37%, 31% and 27%, respectively. Overall survival rates were 72%, 58% and 48%, respectively, with a 48-month overall survival rate of 42%.

In an analysis, researchers assessed an outcome they called progression-free survival 2 (PFS2), which was defined from the time when a patient was assigned a particular treatment until disease progression on the second immediate line of therapy, during a median follow-up of 25.3 months. The median PFS2 in the combination arm was 28.4 months compared with 20.1 months in the monotherapy arm.

For patients receiving Opdivo plus Opdualag, the 12-, 24-, 36-, and 48-month PFS2 rates were 71%, 54%, 46% and 42%, respectively. For patients receiving single-agent Opdivo, the 12-, 24-, 36-, and 48-month PFS2 rates were 62%, 46%, 36% and 35%, respectively.

The overall response rate (the percentage of patients with a complete or partial response to treatment) difference between the two arms was 9.8% with those in the doublet arm experiencing an overall response rate of 44% compared with 34% in the monotherapy arm. Progressive disease (cancer that grows, spreads or worsens) occurred in 31% of patients versus 42%, respectively. The complete response rates (the disappearance of all signs of cancer from treatment) were both 18%, stable disease rates (cancer that does not increase or decrease in severity) were both 16%, and median duration of response (the time from treatment response to disease progression or death) was not reached in either arm.

Melanoma-Specific Survival

“This reflects the same pattern of the (overall survival) arm, and we see a consistent separation of the arms early on and we see a start of a flattening of the curve toward the end,” Tawbi explained. “The difference is a 23% decrease in the risk of death from melanoma.”

Melanoma-specific survival reflected the time of treatment assignment to death of melanoma. Further, causes of death included a study drug toxicity for four patients in the combination arm and two patients in the single-agent arm, as well as unknown causes of seven and 10 patients, respectively. Other causes led to 25 and 19 deaths, respectively, with the most common being septic shock, heart attack, stroke, pneumonia and respiratory insufficiency.

Subsequent Therapy Subgroup

“Importantly, we started looking at subsequent therapy and we see that on both arms of the study there were approximately 46% of patients that received any subsequent therapy. That could have included any modality, so we have radiotherapy and surgery … and subsequent systemic therapy,” Tawbi said.

Of patients in the Opdivo/Opdualag arm (131 patients) and Opdivo arm (136 patients), 40% versus 49% received PD-1/CTLA-4 inhibitors and 37% versus 42% received BRAF or MEK inhibitors, respectively. Tawbi noted that although investigators did not report responses from a substantial number of patients, median progression-free survival between both arms is similar and what would be expected from the combinations.

The subsequent median progression-free survival for patients receiving the doublet who were previously treated with Opdivo plus Yervoy (ipilimumab; 16 patients) was 8.4 months, was 3.4 months for those given Yervoy alone (9 patients) and was 15.4 months for those given BRAF/MEK inhibitors (43 patients).

In the monotherapy arm, the subsequent median progression-free survival for patients who previously received Opdivo plus Yervoy (16 patients) was 2.9 months, was 2.9 months for those given Yervoy (14 patients), and was 10.6 months for those given BRAF/MEK inhibitors (45 patients).

Safety

The updated data were consistent with previous reports and there were no new safety signals. Among patients in the combination arm, 22% experienced severe or life-threatening side effects versus 12% in the monotherapy arm, leading to discontinuation rates of 10% and 4%, respectively. There were four treatment-related deaths in the Opdivo plus Opdualag group and two in the single-agent Opdivo group.

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