Nivolumab induced long-lasting response in stage IV melanoma

  • June 1, 2013

CHICAGO — The investigational antibody nivolumab induced response rates three to six times higher than those reported with other treatments among patients with stage IV melanoma, according to study results presented at the ASCO Annual Meeting.

Thirty percent of patients experienced tumor shrinkage with nivolumab (BMS-936558, Bristol-Myers Squibb), compared with 5% to 10% in studies of other immunotherapy drugs.

“We are really in an era of remarkable advances for melanoma treatment,” Mario Sznol, MD,  professor of medical oncology at the Yale Cancer Center in New Haven, Conn., said during a press conference.

Data from the CA209-003 trial demonstrated nivolumab had significant activity in patients with melanoma, renal cell carcinoma and non–small cell lung cancer. Sznol presented long-term follow-up data related to melanoma.

The cohort included 107 patients assigned to one of five doses of nivolumab: 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg. Sixty-three percent of patients had undergone two or more prior therapies, and 25% had undergone three or more therapies.

Median OS was 16.8 months across all doses. The 1-year OS rate was 62% and the 2-year OS rate was 43%.

The overall response rate was 31% among the entire cohort and 41% among patients assigned to the 3 mg/kg dose, which was chosen for further development, Sznol said.

“The median duration of response was 2 years and is one of the highest that I have seen. I can honestly say that [nivolumab] is one of the best-tolerated drugs I have given in the clinic,” Sznol said. “The activity wasn’t restricted only to patients who just had an objective response. An additional 11% of patients either had prolonged state of disease or these unconventional patterns of response … suggesting that there was activity above the 31% that had an objective response.”

Nivolumab is currently being investigated in three ongoing phase 3 trials in melanoma, Sznol said.

For more information:

Sznol M. Abstract #CRA9006. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.

Disclosure:  The researchers report research funding or honoraria from, employment relationships with, consultant or advisory roles with, or stock ownership in Amplimmune, Bristol-Myers Squibb, Dendreon, Genentech, ImClone, Lilly, Merck, Roche and other pharmaceutical companies.

Nikhil I. Khushalani, MD

Nikhil Khushalani

  • The mature follow-up data on nivolumab confirm the high activity and, importantly, the durability of response and tolerance to this immune checkpoint (PD1) inhibitor. What is most impressive is that more than a third of patients with advanced disease treated with nivolumab were alive at 2 years, more than double that of historical controls with other drugs used in the past — and this, despite the fact that many patients had already received multiple other lines of therapy prior. It is now incumbent on us to move this drug to the front-line setting and also rationally combine it with other agents in order to continue raising the bar in melanoma therapeutics. Provider and patient education is very important to recognize immune-mediated toxicity from this drug (eg, pneumonitis) and adopt appropriate intervention strategies.

    • Nikhil Khushalani, MD
    • Section chief of soft tissue and melanoma
      Associate professor or oncology
      Roswell Park Cancer Institute
      Buffalo, N.Y.
  • Disclosures: Khushalani reports grant funding from the National Comprehensive Cancer Network from general research support provided by Allos, Pfizer and Roche; funding for investigator-initiated clinical trials from Merck and Pfizer; a speaker’s bureau role with Prometheus and an advisory board role with Genentech.
Gregory Masters, MD

Gregory A. Masters

  • There are a number of new drugs available for the treatment of melanoma. Our ongoing efforts will have to be directed toward determining which patients to treat with these therapies. It’s exciting to see that we can do that with less and less toxicity.

    • Gregory A. Masters, MD, FACP

    • Director, medical oncology fellowship
      Medical Oncology Hematology Consultants
      Member, ASCO Cancer Communications Committee
  • Disclosures: Masters reports no relevant financial disclosures.