Long-term follow-up results from an expanded phase I study 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 percent, but 30 percent of patients experienced tumor shrinkage in this study.

Nivolumab targets the PD-1 receptor, an immune system gatekeeper or “checkpoint” on the surface of T-cells, releasing the brakes on the immune system and boosting its ability to fight off cancer.

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, a professor of medical oncology at the Yale Cancer 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.”

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 percent had three or more prior therapies and 63 percent had two or more. Overall, 33 out of 107 (31 percent) of patients experienced tumor shrinkage of at least 30 percent and responses were seen at all doses.

The estimate for survival at two years was 43 percent. The median overall survival across all doses was 16.8 months; 20.3 months for the dose 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 overall survival 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 Lynn Schuchter, MD, ASCO spokesperson and melanoma expert.

“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,” said Dr. Sznol. Another reassuring point, according to Dr. 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.

This research was supported by Bristol-Myers Squibb.

Source: ASCO