Melanoma: New Drugs and New Challenges (Part 1 of 2)


New targeted and immunotherapy drugs have changed the diagnosis of metastatic melanoma from a death sentence into a disease that can potentially be managed and even cured. Nevertheless, these new drugs do not work in all patients, or they may stop working after a transient response. This post (part one of two) will describe ongoing efforts to find drug combinations with higher efficacy than single drugs and decipher the mechanisms underlying drug resistance. Continue reading…


Lung Cancer Highlights from ASCO 2016


This year, the Annual Meeting of the American Society of Clinical Oncology (ASCO) did not produce any truly groundbreaking revelations about new treatments for lung cancer. However, researchers did report quite a few positive findings, and some disappointing ones. I have summarized some of the more prominent presentations below. Continue reading…


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.”

Go to full article.

Do you have questions about this story? Let us know in a comment below. If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our Ask Cancer Commons service.


Targeted Therapy Combinations Still Key in Metastatic Melanoma

“Combinations of targeted therapies continue to advance toward full regulatory approval for patients with metastatic or unresected melanoma, given the substantial benefits seen with these agents. At this time, the FDA is considering two applications for separate combinations of BRAF and MEK inhibiting agents for patients with unresectable or metastatic BRAFV600 mutation-positive melanoma.

“ ‘The future of the treatment of melanoma is clearly going to be in combinations, both for targeted therapy and for immunotherapy,’ said Jeffrey S. Weber, MD, PhD, who recently joined the NYU Langone Medical Center. ‘Already, there is an FDA-approved combination therapy that is targeted; that is dabrafenib and trametinib. There are new combinations coming up, mainly concerning CDK 4/6 and MEK inhibitors in NRAS-mutated but BRAF wild-type melanoma, which is an unmet medical need.’ “


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.”


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.”


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].”