Long-term follow-up results from an expanded phase I study supported by Bristol-Myers Squibb indicate that nivolumab produces long-lasting responses in patients with stage IV melanoma. Historical response rates to immunotherapy drugs in advanced melanoma are five to 10%, but 30% of patients experienced tumor shrinkage in this study.The study results were presented at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO), being held in Chicago, Il, May 31 – June 4, 2013
The investigational monoclonal antibody nivolumab targets and blocks the PD-1 (programed death-1) receptor, an inhibitory immune gatekeeper or “checkpoint” receptor expressed by activated T cells, 
releasing the brakes on the immune system and boosting its ability to fight off cancer. Nivolumab inhibits the binding of PD-1 with its tumor-expressed ligands, programmed death-ligand 1 (PD-L1/B7-H1) and PD-L2 (B7-DC). Blocking of the interaction of the PD-1 receptor with its ligands may allow T-cells to elicit an anti-tumor immune response. This study affirms immunotherapy as an important treatment approach for melanoma.
?I think nivolumab is a real breakthrough drug for patients with metastatic melanoma, and probably for other diseases, too,? said lead author Mario Sznol, MD (photo 1, right), a professor of medical oncology at the YaleCancer Center in New Haven, Conn. ?The high level of activity observed with this drug opens up a number of avenues for future research to understand and challenge the ways tumors evade the immune system. We?re very excited that there is potential for even more activity in combination with other drugs.?
Expanded phase I study of nivolumab indicates that the new immunotherapy is very active as a single agent in patients whose disease progressed despite standard systemic therapy.
In this study, 107 patients were treated with five different doses of nivolumab. All patients had disease that worsened 
despite prior standard systemic therapies ? 25% had three or more prior therapies and 63% had two or more. Overall, 33 out of 107 (31%) of patients experienced tumor shrinkage of at least 30% and responses were seen at all doses. The estimate for survival at two years was 43%.
The median overall survival across all doses was 16.8 months; 20.3 monthsfor thedose chosen for study in subsequent clinical trials. While this is an 
early-phase study, and the results cannot be directly compared to those with other drugs, the results are striking, with median overallsurvival exceeding that seen with the most recently approved melanoma drugs.
?Results confirm that ?revving? up the immune system is a powerful approach in shrinking melanoma. Melanoma patients are living longer and better with these new treatments. Truly remarkable,? said LynnSchuchter, MD (photo 2, left), melanoma expert and ASCO spokesperson.
?While this was not a randomized clinical trial, it had a considerable number of patients and the durability of responses is a sign of very promising clinical activity,? Sznol said.
Another reassuring point, according to Sznol, is that patients in this clinical trial are representative of typical patients with advanced melanoma ? the investigators did not select for the very best patients. Randomized phase III trials have been initiated to confirm these findings.
More research is needed to identify molecular markers that can help predict which patients are most likely to benefit from nivolumab. One potential marker is the protein PD-L1 on the surface of tumor cells, which is being studied in several other clinical trials.
For more information:
Abstract #CRA9006: Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma
(MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538).
Oral Abstract Session: Melanoma/Skin Cancers StudyAuthor: Mario Sznol, MD,Yale Cancer Center,New Haven, CT
Date: Saturday, June 1, 2013, 03:15 ? 03:30 PM CDT
Location: Room: S406
Photo 1:Mario Sznol, MD; Photo 2: Lynn Schuchter, MD. Photo Courtesy:? ASCO/Scott Morgan 2013.
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