High-risk Stage III melanoma patients to benefit from Australia/Netherlands collaboration

High-risk Stage III melanoma patients to benefit from Australia/Netherlands collaboration

23 October 2018

Research that could change clinical practice for high-risk Stage III melanoma patients has been presented at the European Society for Medical Oncology (ESMO) Congress in Munich.

The OpACIN-Neo study, led by a team out of the Netherlands with a large number of patients recruited from Melanoma Institute Australia, showed a modified combination of the immunotherapies ipilimumab and nivolumab given prior to surgery produced a response in over 70% of patients. Importantly, there were drastically reduced side effects for patients and remarkably, none of these patients have relapsed to date.

Stage III patients are those whose melanoma has spread to their lymph nodes. Standard therapy for these patients is to undergo surgery to remove their melanoma, however those who undergo surgery alone have a significant risk (40-70%) of their disease recurring and progressing to Stage IV. Research in Stage IV melanoma patients demonstrates that combining ipilimumab and nivolumab is more effective than nivolumab alone, however this combination of drugs often causes extreme side effects for patients with many unable to continue treatment. Extrapolating from this data, the OpACIN-Neo study aimed to modify the dose of combined ipilimumab and nivolumab to reduce the incidence of toxicity while extending the efficacy seen in Stage IV patients to those with high-risk Stage III disease.

Previous research has shown that giving immunotherapy prior to surgery shrank the number of melanoma cells and increased long-term relapse-free survival. Neoadjuvant (pre-surgery) ipilimumab and nivolumab was also found to induce a stronger immune response, leading researchers to believe that when the immunotherapy is able to see the melanoma cells, they are able to assist the immune system to mount a more effective response.

In the OpACIN-Neo trial, researchers modified the standard dosing schedule by decreasing the dose of ipilimumab and increasing the dose of nivolumab and gave these prior to surgery. They found that after six weeks of therapy, the toxicity of the combination therapy was drastically reduced (only 20% of patients suffered a severe toxicity compared with those who received the standard dosing in that 6 weeks) while the efficacy was largely unchanged with a pathologic response seen in 77% of patients.

"These results are promising in that they provide an insight into the effects of altering the dosage and timing of giving combination immunotherapy to Stage III melanoma patients," said Co-Medical Director of Melanoma Institute Australia, Professor Georgina Long. "To have such a high level of response, coupled with greatly reduced toxicity for patients, means we are heading in the right direction with this vital area of immunotherapy research. The high rate of pathological response is exciting, as we know from a pilot study that those patients who had a pathological response haven’t had disease recurrence."

Stage III melanoma patients with bulky lymph node disease have the worst prognosis of Stage III patients, with 70-80% of them expected to recur within the first two years. After three years of follow-up in this pilot study, every patient who presented with a pathological response is yet to recur.

Promising results from a host of clinical trials investigating the use of neoadjuvant therapies in metastatic melanoma are being analysed by the International Neoadjuvant Melanoma Consortium, which also met at ESMO. This international group of researchers and clinicians aims to increase collaboration and standardise efforts in neoadjuvant treatment for melanoma. "This is one of the most exciting things happening in drug therapy in melanoma and has the capacity to ultimately change clinical practice around the world," Professor Long added.

International collaboration the key to increasing survival
24 Oct 2018

International collaboration the key to increasing survival

"International collaboration remains the key to ensuring this pioneering research continues so we can increase survival rates for advanced melanoma patients and move us closer to achieving our goal of zero deaths from melanoma," says Professor Georgina Long, of the clinical trial results presented at ESMO 2018.

High-risk Stage III melanoma patients to benefit from Australia/Netherlands collaboration
23 Oct 2018

High-risk Stage III melanoma patients to benefit from Australia/Netherlands collaboration

Research that could change clinical practice for high-risk Stage III melanoma patients has been presented at the European Society for Medical Oncology (ESMO) Congress in Munich.

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Professor John Thompson awarded prestigious 2018 RPA Foundation Research Medal

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MIA Scoops Awards at the International Academy of Pathology
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A weekend in Paris talking all things pathology...
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An international course on melanoma pathology in Paris, France co-directed by Professor Richard Scolyer took place over the weekend.