When oncologists discuss melanoma patients’ options with them following treatment, it’s often not clear whether adjuvant therapy is the best choice. Patients must consider whether it’s worth enduring side effects or relying on close monitoring in the event of recurrence. “The big question is always whether there’s an advantage to trying it in the adjuvant setting,” said Paul B. Chapman, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York who specializes in treating melanoma. What’s unknown, he said, is if their chances of long-term survival are similar to patients who are carefully watched and treated when the cancer returns.
Yet the authors of new research on targeted therapies dabrafenib plus trametinib wanted to see if there was a long-term benefit to taking them. This was especially the case given that previous phase 3 results of the COMBI-AD trial that was sponsored by GlaxoSmithKline (and later Novartis who bought the drugs) had shown that patients with resected stage 3 melanoma with BRAF V600E or V600K mutations who took these therapies for 12 months experienced a longer relapse-free survival than those who took a placebo.1 Now they wanted to know: Would a year’s worth of medication continue to provide a benefit, long after patients had stopped taking them?
“Melanoma patients with a complete resection of all detectable tumor manifestation have a high risk to relapse,” said Reinhard Dummer, MD, Professor of the University of Zurich and Vice Chairman of the Department of Dermatology at the University Hospital of Zürich. “The question is, whether systemic therapy using a kinase inhibitor for a limited time can have a long-term beneficial effect in this patient population.”
Dr Dummer was the principal investigator of a study that was published last month in The New England Journal of Medicine that followed 870 patients for 5 years and found that 52% of patients who took dabrafenib plus trametinib were alive without relapse, compared with 36% with placebo.2 Sixty-five percent of participants survived without distant metastasis with the 2 targeted therapies, vs 54% for placebo. “The 5-year landmark is very important because we assume the patients who do not relapse within 5 years will be disease free for a very long time. So this means they are potentially cured,” he said.
Although the extent of the long-term benefit seen in patients varied according to how they well they responded to the therapy — and how well they tolerated the drugs — the study found they experienced no long-term toxicities. The combination of dabrafenib plus trametinib has been linked to the following side effects: new skin cancers, inflammation of the intestines, blood clots, fever, increased blood sugar, and problems with internal bleeding, eyes, breathing, and the heart.
Dr Dummer said he was surprised that patients continued to benefit from the targeted therapies for many years after taking only a year-long course of the adjuvant drugs. He added that his study is important to the field because it’s the first clinical trial to capture long-term follow-up data of an adjuvant therapy. Future research should focus on the individual features of the patients, given that molecular analyses of patients’ tumors has identified subpopulations who responded well to the drugs and those who didn’t. “Intensive treatment options should be developed for patients with a limited benefit in order to increase the cure rates,” he said.