Targeted BRAF/MEK Inhibitor Combination Achieves Long-Term Survival in Melanoma

Excerpt:

“More than one-fourth of patients with advanced BRAF V600-mutant melanoma remained alive at 5 years after treatment with the combination of dabrafenib (Tafinlar) and trametinib (Mekinist), long-term follow-up from a randomized trial showed.

“In the subgroup of patients with normal baseline lactate dehydrogenase (LDH) and fewer than 3 organ sites with metastases, half remained at alive at 5 years. No new safety signals emerged during long-term follow-up, as reported at the 2017 ASCO Annual Meeting in Chicago.”

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Long-Term Survival Possible With MAPK Inhibition in BRAF-Mutant Melanoma

“Long-term outcomes for BRAF-mutant melanoma patients treated with BRAF and MEK inhibitors are influenced by a number of baseline factors including BRAF genotype, gender, and serum lactate dehydrogenase (LDH) levels, according to a new study.

“Treatment of V600 BRAF-mutant metastatic melanoma has improved with inhibition of the MAPK pathway with BRAF inhibitors and MEK inhibitors. But ‘the degree of response and the duration of survival are highly variable,’ wrote study authors led by Alexander M. Menzies, MBBS, of the Melanoma Institute Australia in Sydney. ‘Whether clinicopathologic factors can be used to predict the clinical course of these patients is largely unknown, and there have been few studies examining this issue.’

“The study included 142 consecutive immunotherapy- and MAPK inhibitor–naive patients with BRAF-mutant metastatic melanoma. All were treated either with BRAF inhibitors (111 patients) or with a combination of dabrafenib and trametinib (31 patients), and the median follow-up was 15.7 months. Results were published online ahead of print in Cancer.”


A New Prognostic Test for Patients with Metastatic CRPC

“In an analysis reported in the Journal of Clinical Oncology, Scher et al found that circulating tumor cell count and LDH level served as an individual-level surrogate for survival among patients with metastatic castration-resistant prostate cancer receiving abiraterone acetate (Zytiga) plus prednisone vs prednisone in the phase III COU-AA-301 trial.

“The double-blind COU-AA-301 trial included 1,195 patients previously treated with paclitaxel. The current analysis includes 711 patients (484 in the abiraterone-prednisone group, 227 in the prednisone group) with available 12-week biomarker data. Biomarker analysis was a secondary objective of the trial.

“The combination of circulating tumor cell count and LDH level at 12 weeks was shown to satisfy the four Prentice criteria for individual-level surrogacy (ie, treatment must have a significant effect on the clinical endpoint and a significant effect on the biomarker, the biomarker must have a significant impact on the endpoint, and the full effect of treatment on the endpoint must be captured by the biomarker)…

“The investigators concluded: ‘A biomarker panel containing [circulating tumor cell] number and LDH level was shown to be a surrogate for survival at the individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone alone for patients with metastatic [castration-resistant prostate cancer]. Additional trials are ongoing to validate the findings.’ ”


Imaging Tumor Blood Vessels Could Help Optimize Melanoma Treatment

Melanomas that have spread can be treated by cutting off their blood supplies, but this only works in some people. Now there may be a way to predict who this anti-angiogenic therapy will benefit, according to findings reported at the American Association for Cancer Research’s 2013 meeting. The researchers analyzed computed tomography (CT) images of melanomas from 46 people who had undergone anti-angiogenic treatment. The images revealed that loss of tumor blood vessels was linked to survival, particularly in people who also had low levels of lactate dehydrogenase (LDH). Next, the researchers plan to test their findings in clinical studies.


CT and serum LDH shows promise as survival predictor for some metastatic melanoma patients

“Combining CT imaging findings with baseline serum lactate dehydrogenase levels is showing promise as a way to predict survival in patients with metastatic melanoma being treated with anti-angiogenic therapy…”


Elesclomol May Benefit Chemotherapy-Treated Melanoma Patients with Normal LDH Levels

A phase III trial showed that the combination of elesclomol and paclitaxel did not benefit most people with melanoma. Elesclomol is an experimental drug that can kill cancer cells and paclitaxel is a chemotherapy drug. The trial included 651 people; the combination treatment was stopped early when it became clear that most of those treated with paclitaxel alone survived longer. Most of these people also had high levels of an enzyme called lactate dehydrogenase (LDH). Conversely, elesclomol did increase survival in people with normal levels of this enzyme, suggesting that LDH levels could be used to predict who would benefit from this combination treatment.