Immunotherapy combo appears effective in advanced melanoma

31 May 2015

Treating advanced melanoma patients with either a combination of the immunotherapy drugs nivolumab (Opdivo™) and ipilimumab (Yervoy™) or nivolumab alone significantly increases progression-free survival (PFS) over using ipilimumab alone, according to new findings from researchers at Memorial Sloan Kettering Cancer Center (MSK). Examining specific characteristics of each patient's tumor has also given researchers clearer understanding of which patients should receive the combination.

“Combining these two immunotherapy drugs could result in better outcomes for patients”

Jedd Wolchok, Chief of MSK's Melanoma and Immunotherapeutics Service, designed and led the phase 3 randomized, double-blind trial, in which 945 patients with untreated advanced melanoma were randomized to receive ipilimumab alone, nivolumab alone, or a combination of the two.

While this study was not designed for a formal statistical comparison between the nivolumab group and the combination group, exploratory analyses revealed more frequent responses and longer PFS in the combination group when compared with nivolumab alone. Patients receiving the combination experienced a median PFS of 11.5 months, while median PFS for patients receiving nivolumab alone was 6.9 months and ipilimumab alone was 2.9 months.

In particular, of the 314 patients receiving the combination:

  • 57.6% had an objective response, measured as a significant reduction in tumor size, versus
  • 43.7% of the 316 receiving nivolumab alone and
  • 19% of the 315 receiving ipilimumab alone.

"All the early preclinical and clinical work supported the idea that combining these two immunotherapy drugs could result in better outcomes for patients," said Dr. Wolchok.

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What about the side effects?

Adverse side effects such as diarrhea and increased lipase occurred in 55% of patients receiving the combination -- leading about one-third of these patients to stop the regimen. About 16% of patients receiving nivolumab alone and 27% of patients receiving ipilimumab alone experienced side effects, with nearly 8% and 15% of patients discontinuing, respectively.

Ipilimumab and nivolumab are part of a class of drugs called immune checkpoint inhibitors, which unleash patients' immune system to attack their cancer. Ipilimumab works by blocking the CTLA-4 checkpoint, a molecular brake that stops T cells from becoming fully and persistently activated. Similarly, nivolumab prevents the molecule PD-L1, expressed by tumors, from binding to T cells and deactivating them.

One step closer to “precision immunotherapy”

"One of the biggest questions in the field of immunotherapy has been how to determine which patients will respond to immune-modulating drugs. Now we have another piece of data," said Dr. Wolchok. "A simple pathology test can identify patients, whose tumors express PD-L1, and this information will help the patient and physician decide whether to use the combination or nivolumab alone, knowing the toxicity risks and the difference in PFS. However, if a patient's tumor does not express PD-L1, the data suggests it makes more sense to offer the combination. This understanding gets us closer to 'precision immunotherapy.'"

Source: Science Daily
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