Treating Patients With Melanoma With Targeted Therapies Before Surgery Can Delay Relapse

Researchers at The University of Texas MD Anderson Cancer Center recently reported in Lancet Oncology that a pair of targeted therapies given before and after surgery for melanoma produced a 6-fold increase in time to progression of the disease, compared with standard-of-care surgery for patients with stage 3 melanoma. Patients who showed no sign of disease at the time of surgery after receiving combination treatment did not progress to metastasis.

Early results of the study that compared surgery to pre- and post- surgical treatments with the BRAF inhibitor dabrafenib, and the MEK inhibitor trametinib, showed such positive results that the data safety monitoring board at MD Anderson ordered the randomized, prospective phase 2 trial to be halted, and changed it to a single-arm study using the combination.

“These results are encouraging for patients with surgically resectable stage 3 melanoma, who face a high rate of relapse and progression to metastatic disease,” said lead author of the study, Rodabe Amaria, MD, assistant professor of melanoma medical oncology. “Our proof-of-concept study strongly supports further assessment of neoadjuvant (presurgical) therapy for this high-risk population, which has a 5-year survival rate of less than 50%.”

The FDA approved the targeted combination therapy for stage 4 metastatic melanoma that features a BRAFV600 mutation in June 2017. Authors of the study postulate that the combination could potentially help patients with stage 3 BRAF-mutant disease.

The clinical trial was launched through the Melanoma Moon Shot, part of MD Anderson's Moon Shots Program to accelerate cancer treatment and prevention. The 84 patients enrolled were either randomized to up-front surgery or to 8 weeks of targeted therapy followed by surgery and another 44 weeks of treatment. The analysis occurred after 21 patients were treated. The 7 patients treated with standard-of-care surgery had a median time to progression at 2.9 months. The median time to progression for the 14 patients treated with the combination therapy first was 19.7 months. Half of the patients in the group that received the targeted therapy first achievd pathological complete response.

“As we accumulate more data, we can further explore the importance of pathological complete response,” said senior author Jennifer Wargo, MD, associate professor of Surgical Oncologyand Genomic Medicine. “If we can prove that pathologic complete response is important in achieving superior outcomes, then the next step is to ask ‘what can you do to get to pCR?’”