Opdivo increased survival in pre-treated melanoma

Opdivo increased survival in pre-treated melanoma

17 Apr 2016

A third of patients with previously treated melanoma lived 5 years or longer after receiving the immunotherapeutic agent nivolumab (Opdivo), according to data. The 107 patients in the trial had a 5-year overall survival of 34%. Survival appeared to reach a plateau at about 48 months.

In a subgroup of patients who had retreatment with nivolumab, disease control remained durable, reinforcing the view that treatment with an immune checkpoint inhibitor induces a memory effect on the immune system. No new or unexpected safety issues emerged from the trial, said F. Stephen Hodi, MD, of Dana-Farber Cancer Institute in Boston. "These data represent the longest survival follow-up of patients who received anti-PD-1 therapy in a clinical study, and suggest durable, long-term survival with nivolumab monotherapy," Hodi said.

Nivolumab, an inhibitor of programmed death-1 (PD-1), has demonstrated efficacy in melanoma and other advanced malignancies. In the U.S., the drug's approved indications include use as a single agent or in combination with ipilimumab (Yervoy) for first-line treatment of advanced melanoma.

The longest survival follow-up to date for an anti-PD-1 agents

Hodi reported findings from long-term follow-up in a trial of the PD-1 inhibitor in patients with advanced melanoma that had progressed on prior therapy. The trial has accumulated the longest survival follow-up to date for an anti-PD-1 agents, he said.

The trial involved 107 patients with advanced melanoma that had progressed on at least one and as many as five prior lines of therapy. They received one of five doses of nivolumab, and treatment continued for as long as 96 weeks. The primary objective of the trial was safety and tolerability. Secondary objectives included preliminary efficacy and dose-response relationships. As an exploratory analysis, investigators examined outcomes of patients who were retreated with nivolumab.

Clinical results

Data analysis for survival occurred after a median follow-up of 45 months. Almost 2/3 of the patients had received at least two prior regimens, and a fourth had received three or more prior regimens. Prior treatment included an immunotherapeutic agent (other than CTLA-4 or PD-1 inhibitors) in two thirds of cases, most often interleukin-2. In particular, scientists reported that:

  • The entire cohort had a median overall survival of 17.3 months
  • 34% of the patients survived 5 years or longer
  • 5 patients in the trial received a second exposure to nivolumab (at the same dose as initial treatment) after being off treatment for more than 100 days.
  • Patients eligible for treatment had disease progression after initial disease control; had no dose-limiting toxicity during initial treatment; did not reach the 1-year mark of follow-up without disease progression; and had not previously undergone retreatment.


"In all five patients, disease control was obtained again, and this disease control was once again durable," Hodi said. "One patient remains on treatment. One patient had an adrenal metastasis, and when that site was removed, the patient basically had no more evidence of disease. This has led to a long-term durable benefit, suggesting some of the memory aspects of giving checkpoint blockade and its adaptability long term to help patients."

The findings emphasize the distinguishing feature of nivolumab and immunotherapy, in general, from other types of systemic therapy for cancer, said press briefing moderator Louis M. Weiner, MD, of the Georgetown Lombardi Comprehensive Cancer Center in Washington. "People who have good responses really seem to be protected against the disease returning in many cases. Not in every case, but in many cases," Weiner said. "This is in marked distinction to many of our chemotherapy approaches or targeted therapy approaches, where you can see more rapid development of resistant disease. The memory of the immune system, and the adaptability of the immune response to take off resistant variants that may be trying to develop, is a really important take-home point, and these are really compelling data to suggest this is the case."


Source: MedPage Today

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