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ESMO 2014: Nivolumab Shows Signs of Superior Response Rate Compared to Standard Chemotherapy in Advanced Melanoma

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Key Points

  • In patients with metastatic melanoma who progressed after ipilumumab treatment, preliminary data show that nivolumab has markedly higher clinical activity vs chemotherapy, with a 32% response rate.
  • Treatment responses were also longer-lasting in the nivolumab group compared to the chemotherapy group.
  • There was a 31% incidence of higher-grade treatment-related side effects in the chemotherapy group compared to only 9% incidence in the nivolumab group.

The monoclonal antibody nivolumab achieved superior response rates and a longer duration of response than standard chemotherapy in patients whose melanoma has progressed after treatment with ipilimumab (Yervoy), according to preliminary data from a phase III trial presented at the ESMO 2014 Congress in Madrid (Abstract LBA3_PR).

“Previously-treated advanced melanoma patients have limited options,” said the study’s principal investigator, Jeffrey S. Weber, MD, Director of the Donald A. Adam Comprehensive Melanoma Research Center of Excellence at Moffitt Cancer Center, Tampa, Florida.

Nivolumab is a programmed death (PD)-1 immune checkpoint inhibitor antibody that has demonstrated durable antitumor activity and promising overall survival in phase I trials of pretreated patients with melanoma.

Phase III Trial

In this first phase III trial of nivolumab among melanoma patients whose disease has progressed even after treatment with ipilimumab, 405 patients with unresectable metastatic melanoma were randomly assigned in a ratio of 2:1 either to intravenous nivolumab (3 mg/kg) or the investigator’s choice of chemotherapy regimens: dacarbazine (1,000 mg/m2) or carboplatin AUC6 plus paclitaxel (175 mg/m2).

The primary endpoints of the study were objective response rate to treatment and overall survival, but researchers also looked at the impact of treatment on secondary objectives of safety, progression-free survival, health-related quality of life, and expression of the programmed death-1 ligand (PD-L1).

Preliminary data from a subgroup of the nivolumab-treated patients in the open-label trial show that nivolumab has markedly higher clinical activity with a 32% response rate, as well as lower toxicity compared to the chemotherapy reference arm, with a 11% response rate.

Treatment responses were also longer-lasting in the nivolumab group compared to the chemotherapy group, and there was a 31% incidence of higher-grade treatment-related side effects in the chemotherapy group compared to only 9% incidence in the nivolumab group.

“The impressive data on duration of response suggest that there will be significant prolongation of progression-free and overall survival when the analysis of those data is mature,” said Dr. Weber.

Further Support for PD Blockade

In summary, Dr. Weber said, “The differences in response rate and toxicity markedly favor the use of the PD-1 blocking antibody nivolumab compared to results seen with chemotherapy in patients [in whom ipilimumab treatment has] failed.”

Commenting on the findings, Olivier Michielin, MD, PhD, of the Department of Oncology, University of Lausanne, Switzerland, said, “These results add another piece of evidence that PD blockade is rapidly becoming a central part in our armamentarium against melanoma, progressively replacing chemotherapy with more effective and less toxic options.”

“These results demonstrate that PD blockade, contrary to a common and old dogma of immunotherapy, can produce rapid and deep responses even in advanced and bulky disease. This opens exciting new opportunities to widen the scope of application of immuno-oncology for the treatment of stage IV melanoma,” said Dr. Michielin.

For full disclosures of the study authors, view the study abstract at www.esmo.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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