29 November 2017

The changing face of melanoma treatment

Cancer Clinical

We may soon be able to stop melanoma in its tracks, thanks to promising new Australian research.

Professor Richard Scolyer, the co-medical director of the Melanoma Institute Australia, described recent developments in targeted and immunotherapies as “incredible”.

Only a few years ago, the five-year survival outcomes for people with cerebral metastases from their melanoma was less than 5%, he told audience members at a Royal College of Pathologists of Australasia event for International Pathology Day.

“Most people would only be alive for six weeks, but now 50% of the people are alive at two and three years,” he said. “So we know we are making a big, big difference to these people.”

The Melanoma Institute Australia recently published the results of two major trials, the COMBI-AD and CheckMate 238, which indicated treatments were able to reduce the spread of disease, post-surgery in patients with stage III melanomas.

This meant high-risk patients with lymph gland involvement could soon be treated with these medications, which were currently only approved for stage IV melanoma patients, Professor Scolyer said.

In an accompanying editorial in the NEJM, US medical oncologist Associate Professor Lynn Schuchter called the developments in adjuvant therapy “head spinning”.

“With these new approaches, some patients have been cured, and many have seen remarkable improvements in symptoms and quality and duration of life,” she said.

“The median overall survival of patients with disseminated melanoma has increased from nine months before 2011 to two years or more.”

The COMBI-AD trial compared adjuvant use of dabrafenib and trametinib, the BRAF and the MEK inhibitors, to a double placebo, and found that recurrence was 53% lower in the treatment group.

The CheckMate 238 study compared nivolumab with ipilimumab, a treatment that already improves survival, in BRAF-mutated patients and found that nivolumab patients had a 13% absolute increase in relapse-free survival.

“Both [trials] have shown a clinically meaningful reduction in risk of recurrence. And on the basis of these results, our care for patients with node-positive melanoma will now change for the better,” Professor Schuchter wrote.

“Adjuvant therapy with nivolumab in patients with node-positive melanoma may now be considered a new standard of care, regardless of BRAF mutation status.”

Given its efficacy and safety, nivolumab is “unequivocally” a better choice than interferon or high-dose ipilimumab, she said.

“Adjuvant combination therapy with dabrafenib and trametinib is also an option for patients with node-positive, BRAF-mutated melanoma,” she said.

“Testing of melanoma tumours for the presence of BRAF mutations may now become standard in patients with node-positive, stage III melanoma.”

The time for using adjuvant interferon in these patients was over, she added.

“This will change how melanoma is treated around the world, as we no longer have to passively wait to see if the melanoma spreads,” Professor Georgina Long, lead author of one of the studies, said in a statement.

She said it was now possible to “actively and effectively attack the melanoma at an earlier stage, reducing the dreadful anxiety for patients about progressing to a potentially terminal illness and ensuring they have much better outcomes”.

These study results indicated we were significantly closer to changing melanoma from a terminal illness to a chronic disease, she said.

Patients interested in signing up to clinical trials can use the ClinTrial Refer Melanoma available on the Melanoma Institute website.

References:

NEJM 2017;377:1813-23

NEJM 2017;377:1824-35

NEJM 2017;377:1888-90