3-Year Follow-Up Data for Dabrafenib/Trametinib Confirm Results of Combo in Melanoma

Excerpt:

“Three-year follow-up data from the phase III COMBI-d study was presented at the 2016 ASCO Annual Meeting, revealing impressive overall survival (OS) and progression-free survival (PFS) data for the dabrafenib (Tafinlar) and trametinib (Mekinist) combination therapy for patients with BRAF-mutant metastatic melanoma.

“At the February 15, 2016 data cutoff for the 3-year analysis, 58% of patients remained on therapy. The 3-year PFS rate with the combination was 22% versus 12% with single-agent dabrafenib. The 3-year OS rate was 44% with dabrafenib plus trametinib compared with 32% with dabrafenib alone.

” ‘This is the longest OS follow-up among randomized phase III trials evaluating a BRAF plus MEK inhibitor in patients with BRAF-mutant metastatic melanoma,’ said lead investigator Keith T. Flaherty, MD, Massachusetts General Hospital Cancer Center and Professor of Medicine, Harvard Medical School. ‘With additional follow-up, and now 3-year maturity, dabrafenib plus trametinib continued to show significant benefit over dabrafenib monotherapy, despite crossover.’ ”

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Dabrafenib/Trametinib Combo Highly Effective in BRAF-Mutant NSCLC

Excerpt:

“The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) was highly effective as a treatment for patients with BRAF V600E-mutant non–small cell lung cancer (NSCLC), according to lead investigator David Planchard MD, PhD, who presented the phase II data at the 2016 ASCO Annual Meeting.1 Findings from the study were also concurrently published in Lancet Oncology.2

“The investigator assessed objective response rate (ORR) with the combination was 63% (95% CI, 49-75), which lasted for a median duration of 9.0 months (95% CI, 6.9-18.3). When adding those with stable disease for ≥12 weeks, the overall disease control rate was 79% (95% CI, 66-89). The median progression-free survival (PFS) was 9.7 months (95% CI, 6.9-19.6).

“In addition to the combination cohort, the study also included a single-agent arm that included 78 previously treated patients with metastatic BRAF V600E–mutant NSCLC. In this cohort, the ORR with single-agent dabrafenib was 33% and the median PFS was 5.5 month. Findings from both cohorts of the study have led to breakthrough therapy designations from the FDA for dabrafenib as a single agent and in combination with trametinib.”

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Dabrafenib Active in BRAF-Mutant Metastatic NSCLC

Excerpt:

“Planchard et al found that the BRAF kinase inhibitor dabrafenib (Tafinlar) produced responses in previously treated and untreated patients with BRAF-mutant metastatic non–small cell lung cancer (NSCLC), according to a phase II trial reported in The Lancet Oncology. Activating BRAF V600E mutations are found in approximately 1% to 2% of lung adenocarcinomas.”

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Novartis Gets FDA Approval for Skin Cancer Drug Combination

“Nov 20 Novartis AG said on Friday it received the U.S. Food and Drug Administration’s regular approval for a drug combination to treat an aggressive form of skin cancer.

“The FDA approved Tafinlar and Mekinist for treatment of metastatic melanoma based on two years overall survival in patients, the company said.

“The combination was initially approved based on mid-stage data through the FDA’s accelerated approval program, but the approval was contingent on data from late-stage trial.”


Combining Two Targeted Therapies Results in Melanoma Patients Living Significantly Longer

“Latest results from a trial of a combination of two targeted therapies (dabrafenib and trametinib) to treat advanced melanoma have shown that patients are living significantly longer on the combined therapy than patients treated with another drug, vemurafenib, when used alone.

“Professor Caroline Robert, of the Institut Gustave Roussy, Paris, France, will tell the 2015 European Cancer Congress today (Monday) that not only is the median overall survival time longer for patients receiving the combination treatment, but also that 51% of patients receiving the combination treatment are alive after two years, compared to 38% of patients receiving vemurafenib alone.

“Analysis of data up to 13 March 2015 showed that the median overall survival time among patients with metastatic melanoma harbouring V600 mutations in the BRAF gene who received the combination treatment was 25.6 months. Among patients receiving vemurafenib alone, it was 18 months. On the basis of this finding, the European Commission approved the combination of dabrafenib and trametinib for use in Europe for these patients on 1 September 2015.”


ECOG-ACRIN Opens Trial of Treatment Sequencing in Advanced Melanoma

“A new phase III cancer treatment trial has opened for patient enrollment that examines two treatments that work in completely different ways yet have both been shown in previous clinical trials to be effective in treating patients with advanced melanoma, the ECOG-ACRIN Cancer Research Group announced today.

“Half of the patients in the trial will be randomly assigned to begin treatment with an investigational combination of two immunotherapy drugs, given together, that work by unleashing parts of the immune system to kill tumor cells. If the treatment stops working and the disease gets worse, patients will receive a second, different treatment of two other drugs, also given together, that work by blocking molecular pathways that drive tumor cell growth and survival.

“For the other half of the patients in the trial, the scenario will be reversed. They will be randomly assigned to begin treatment with the two molecularly targeted drugs, and if those drugs stop working and the disease gets worse, they will be treated with the investigational immunotherapy combination.

“Researchers in the ECOG-ACRIN Melanoma Committee are conducting trial EA6134 to find out which sequence of treatments provides the best outcome for patients.”


Novartis Presents New Data at ASCO for Zykadia® and Combination of Tafinlar® and Mekinist® in Certain NSCLC Patients with Unmet Needs

“Novartis today announced new data from two Phase II studies of Zykadia® (ceritinib), as well as one Phase II study of Tafinlar® (dabrafenib) in combination with Mekinist® (trametinib) in certain patients with non-small cell lung cancer (NSCLC). Data from these studies were presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“The results of the Zykadia studies – ASCEND-2 and ASCEND-3 – reinforce the efficacy of the medicine in patients with anaplastic lymphoma kinase-positive (ALK+) NSCLC who had received previous treatment with an ALK inhibitor and in those receiving an ALK-targeted therapy for the first time. Overall response rates (ORR) seen in these trials were 38.6% and 63.7%, respectively, based upon investigator assessment. Comparable ORR results were observed in patients with ALK+ NSCLC who entered the studies with brain metastases (33% and 58%, respectively)[1],[2].

“Separately, the study of dabrafenib in combination with trametinib in patients with metastatic BRAF V600E-mutation positive NSCLC who had failed at least one round of chemotherapy demonstrated an ORR of 63% in this population[3].”


AstraZeneca-Novartis Three-Drug Melanoma Treatment Found Safe

“A first-of-its-kind combination of three drugs to treat a deadly form of skin cancer can be taken safely, passing the first hurdle to regulatory approval for a potentially long-lasting treatment.

“The treatment was tested in an early-stage trial that was a collaboration between AstraZeneca Plc and Novartis AG. Researchers combined two drugs, dabrafenib and trametinib — a so-called doublet therapy that has been proven effective in targeting melanomas with mutations in the BRAF gene — with an immune system-based treatment that may prevent the disease from relapsing.

“Dabrafenib, sold as Tafinlar, and trametinib, sold as Mekinist, were developed by GlaxoSmithKline Plc and acquired by Novartis in March. The immune therapy drug, MEDI4736, is being developed by AstraZeneca.

“Melanoma is a rare but deadly form of skin cancer for which a number of drugs have been approved in recent years. Among them are BRAF inhibitors like dabrafenib, which target mutations found in about half of all melanoma patients, as well as immune therapies like Bristol-Myers Squibb Co.’s Yervoy, which unleash the body’s own immune system. Because the immune system can be trained, those therapies may be more durable than other forms of treatment.”


Dabrafenib plus Trametinib Improves Health-Related Quality of Life in Metastatic Melanoma

“The addition of trametinib to dabrafenib improved health-related quality of life and reduced pain in patients with BRAF V600-mutated metastatic melanoma, according to results of a randomized phase 3 study.

“The combination of dabrafenib (Tafinlar, GlaxoSmithKline) and trametinib (Mekinist, GlaxoSmithKline) received accelerated approval from the FDA in 2014 based on the results of a phase 1/2 study that compared the combination with dabrafenib monotherapy. Results from a phase 3 trial later demonstrated significantly improved PFS and objective rate response with the combination vs. dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma.

“In the current analysis, Dirk Schadendorf, MD, of the department of dermatology at the University Hospital Essen in Germany, and colleagues sought to evaluate the effect of the combination on health-related quality of life among patients treated in the phase 3 study.”