In the JournalsPerspective

Ipilimumab improves 5-year survival rate in advanced melanoma

The addition of ipilimumab to dacarbazine doubled 5-year survival in treatment-naive patients with advanced melanoma, according to results of a randomized, controlled phase 3 trial.

Ipilimumab (Yervoy, Bristol-Myers Squibb), a fully human immunoglobulin G1 monoclonal antibody, received FDA approval in 2011 for the treatment of BRAF V600E-mutated unresectable or metastatic melanoma. Since then, ipilimumab has demonstrated excellent efficacy and safety.

Michele Maio, MD, PhD, of the division of medical oncology and immunotherapy in the department of oncology at University Hospital of Siena in Italy, and colleagues evaluated 5-year survival rates of patients treated with ipilimumab as part of a randomized, controlled trial to assess whether the agent is associated with a long-term survival benefit.

In the study, researchers randomly assigned 250 patients to 10 mg/kg ipilimumab plus the chemotherapeutic agent dacarbazine at weeks 1, 4, 7 and 10, followed by dacarbazine alone every 3 weeks through week 22.

The other 252 patients received dacarbazine plus placebo.

Eligible patients were able to receive maintenance ipilimumab or placebo every 12 weeks beginning in week 24. Safety analyses were conducted on patients who survived at least 5 years and were still receiving ipilimumab as a maintenance therapy.

Researchers reported 5-year survival rates of 18.2% (95% CI, 13.6-23.4) for the ipilimumab arm and 8.8% (95% CI, 5.7-12.8) in the control arm.

Forty patients assigned ipilimumab and 20 patients in the control arm survived at least 5 years. Among that subset of patients, those treated with ipilimumab demonstrated higher rates of objective response (50% vs. 35%), partial response (42.5% vs. 35%) and complete response (7.5% vs. 0%).

“[These] data are highly encouraging as they show a doubled survival of patients at 5-years and a plateau in survival at 3-years, in the ipilimumab-treated arm,” Maio told HemOnc Today.

The most common ipilimumab-related adverse events among patients who survived at least 5 years were rash, vitiligo and pruritus. Both cases of grade 3 to grade 4 rash and pruritus developed in the same patient. No grade 4 adverse events occurred. Researchers reported low-grade events that affected the liver, endocrine system and gastrointestinal tract.

“From a practical viewpoint, the evidence reported in this study further supports the role of ipilimumab as a powerful therapeutic tool in first-line advanced melanoma patients, regardless of the BRAF mutational status,” Maio said. “These findings also provide strong support of the well-acknowledged durable efficacy of cancer immunotherapy, and pave the way to additional trials combining the well-established efficacy of ipilimumab with other drugs, hoping to raise the bar of the percentage of melanoma patients who become long-term survivors to their disease.” – by Anthony SanFilippo

Michele Maio, MD, PhD can be reached at University Hospital of Siena, Via Banchi di Sotto, 55, 53100 Siena SI, Italy; email: mmaiocro@gmail.com.

Disclosure: The study was funded by Bristol-Myers Squibb. The researchers report honoraria, research funding and travel expenses from, consulting/advisory and speakers bureau roles with, employment relationships in and stock ownership in Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merck, Novartis, Roche and other pharmaceutical companies.

The addition of ipilimumab to dacarbazine doubled 5-year survival in treatment-naive patients with advanced melanoma, according to results of a randomized, controlled phase 3 trial.

Ipilimumab (Yervoy, Bristol-Myers Squibb), a fully human immunoglobulin G1 monoclonal antibody, received FDA approval in 2011 for the treatment of BRAF V600E-mutated unresectable or metastatic melanoma. Since then, ipilimumab has demonstrated excellent efficacy and safety.

Michele Maio, MD, PhD, of the division of medical oncology and immunotherapy in the department of oncology at University Hospital of Siena in Italy, and colleagues evaluated 5-year survival rates of patients treated with ipilimumab as part of a randomized, controlled trial to assess whether the agent is associated with a long-term survival benefit.

In the study, researchers randomly assigned 250 patients to 10 mg/kg ipilimumab plus the chemotherapeutic agent dacarbazine at weeks 1, 4, 7 and 10, followed by dacarbazine alone every 3 weeks through week 22.

The other 252 patients received dacarbazine plus placebo.

Eligible patients were able to receive maintenance ipilimumab or placebo every 12 weeks beginning in week 24. Safety analyses were conducted on patients who survived at least 5 years and were still receiving ipilimumab as a maintenance therapy.

Researchers reported 5-year survival rates of 18.2% (95% CI, 13.6-23.4) for the ipilimumab arm and 8.8% (95% CI, 5.7-12.8) in the control arm.

Forty patients assigned ipilimumab and 20 patients in the control arm survived at least 5 years. Among that subset of patients, those treated with ipilimumab demonstrated higher rates of objective response (50% vs. 35%), partial response (42.5% vs. 35%) and complete response (7.5% vs. 0%).

“[These] data are highly encouraging as they show a doubled survival of patients at 5-years and a plateau in survival at 3-years, in the ipilimumab-treated arm,” Maio told HemOnc Today.

The most common ipilimumab-related adverse events among patients who survived at least 5 years were rash, vitiligo and pruritus. Both cases of grade 3 to grade 4 rash and pruritus developed in the same patient. No grade 4 adverse events occurred. Researchers reported low-grade events that affected the liver, endocrine system and gastrointestinal tract.

“From a practical viewpoint, the evidence reported in this study further supports the role of ipilimumab as a powerful therapeutic tool in first-line advanced melanoma patients, regardless of the BRAF mutational status,” Maio said. “These findings also provide strong support of the well-acknowledged durable efficacy of cancer immunotherapy, and pave the way to additional trials combining the well-established efficacy of ipilimumab with other drugs, hoping to raise the bar of the percentage of melanoma patients who become long-term survivors to their disease.” – by Anthony SanFilippo

Michele Maio, MD, PhD can be reached at University Hospital of Siena, Via Banchi di Sotto, 55, 53100 Siena SI, Italy; email: mmaiocro@gmail.com.

Disclosure: The study was funded by Bristol-Myers Squibb. The researchers report honoraria, research funding and travel expenses from, consulting/advisory and speakers bureau roles with, employment relationships in and stock ownership in Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merck, Novartis, Roche and other pharmaceutical companies.

    Perspective
    April K.S. Salama

    April K.S. Salama

    New developments in immunotherapies have dramatically changed the treatment landscape for patients with metastatic melanoma in recent years. Ipilimumab (Yervoy, Bristol-Myers Squibb) — the first drug to demonstrate an OS benefit in a phase 3 trial for this population — is now considered a mainstay of treatment for many patients.
    These studies provide confirmation of the potential for a durable benefit in a subset of patients treated with ipilimumab. With data on 5-year survival rates, the study by Maio and colleagues examines one of the longest follow-up analyses reported from a randomized trial in melanoma. The analysis by Schadendorf and colleagues reports on survival data from a pooled analysis of approximately 1,800 patients, the largest analysis of an ipilimumab-treated cohort to date.
    Both of these analyses offer validation of earlier data that suggested ipilimumab resulted in a durable survival benefit for a cohort of patients. Although the benefit is seen in only a minority of patients, newer developments targeting other immune checkpoints — including PD-1 and others — have opened the door for strategies to allow many more patients to benefit.

    • April K.S. Salama, MD
    • Duke University School of Medicine

    Disclosures: Salama reports research funding paid to her institution from Bristol-Myers Squibb.