ASCO 2013: Nivolumab Produces Durable Responses in Patients with Stage IV Melanoma
Long-term follow-up results from an expanded phase I study indicate that nivolumab produced long-lasting responses in patients with stage IV melanoma. Overall, 33 out of 107 patients (31%) treated with five different doses of nivolumab experienced tumor shrinkage of at least 30% and responses were seen at all doses.
Nivolumab is a monoclonal antibody that blocks PD-1, an inhibitory immune checkpoint receptor expressed by activated T cells. The response rate to nivolumab reported in this study surpassed historical response rates of 5% to 10% for immunotherapy drugs in advanced melanoma.
The estimated 1-year survival rate was 62% and the estimated 2-year survival rate was 43%, the study’s lead author Mario Sznol, MD, reported at the 2013 ASCO Annual Meeting (Abstract CRA9006). Dr. Sznol is Professor of Medical Oncology at Yale Cancer Center in New Haven, Connecticut.
‘Breakthrough Drug’
“I think nivolumab is a breakthrough drug for patients with metastatic melanoma, and probably for other diseases, too,” Dr. Sznol said. “A rapid, objective clinical response was seen in these patients and the objective response rate of 31% in heavily pretreated patients with melanoma was a remarkable number.” In addition, another 11% of patients showed clinical activity, suggesting there was a level of activity beyond the 31% that had objective responses.
All patients in the study had disease that worsened despite prior standard systemic therapies—63% had two or more prior therapies and 25% had three or more. In this study, patients received up to 12 cycles of 4 doses each. The different dose levels tested were 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.
Responses occurred fairly quickly and were long-lasting. The median overall survival across all doses was 16.8 months; at the 3 mg/kg dose, which was the dose chosen for study in subsequent clinical trials, the median overall survival was 20.3 months. Although this was an early-phase study, the median overall survival exceeded rates achieved with recently approved melanoma drugs, according to Dr. Sznol.
Durability A Promising Sign
“While this was not a randomized clinical trial, it had a considerable number of patients and the durability of responses was a sign of very promising clinical activity,” Dr. Sznol said.
“Responses don’t necessarily have to be maintained by continuing drug,” Dr. Sznol added. “Out of the 33 responders, 17 stopped for reasons other than progression of disease, for example, completion of therapy. And of those, 12 continued to respond beyond 4 months of stopping the drug. So you don’t necessarily have to maintain these patients with drug in order for the response to persist.”
Generally Well Tolerated
Nivolumab “was generally well tolerated,” Dr. Sznol said. Drug-related adverse events occurred in 82% of patients. Grade 3/4 events occurred in in 21% of patients, and included lymphopenia, fatigue, and increased lipase. The investigators also reported grade 3/4 drug-related diarrhea (2%), endocrine disorders (2%), and hepatitis (1%). No grade 3 or higher drug-related pneumonitis was observed, and no drug-related deaths were reported.
Randomized phase III trials have been initiated to confirm the study findings. The protein PD-L1 on the surface of tumor cells is also being studied in several other clinical trials as a potential marker to help predict which patients are most likely to benefit from nivolumab.
This research was supported by Bristol-Myers Squibb. Dr. Sznol has reported a consultant or advisory role for Bristol-Myers Squibb.
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®.
