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…


Cobimetinib, Vemurafenib Improved Survival in BRAF V600–Mutated Melanoma

Excerpt:

“Combination treatment with cobimetinib and vemurafenib resulted in significantly improved overall and progression-free survival in patients with previously untreated BRAF V600mutated advanced melanoma, according to updated efficacy results of the coBRIM trial published in Lancet Oncology.

“ ‘Patients treated with the combination of cobimetinib and vemurafenib achieved a higher objective response, longer progression-free survival, and longer overall survival compared with patients treated with vemurafenib alone,’ wrote researchers led by Paolo A. Ascierto, MD, of the Istituto Nazionale Tumori Fondazione G Pascale in Naples, Italy. ‘The combination of cobimetinib and vemurafenib was recently approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of advanced BRAF V600mutant melanoma and represents a new standard of treatment for patients with this disease.’ ”

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.


Oxnard Explains Role of BRAF in NSCLC

Excerpt:

“Geoffrey R. Oxnard, MD, specializes in researching molecular mutations in non–small cell lung cancer (NSCLC) with a particular emphasis on prognostic and predictive biomarkers. Oxnard, who is an assistant professor of Medicine at Harvard Medical School and a thoracic oncologist at the Dana-Farber Cancer Institute, spoke with Targeted Oncology about the potential for BRAF-targeting therapies in NSCLC.

“TARGETED ONCOLOGY: What is the potential for utilizing currently available BRAF/MEK-targeted therapies in treating patients with NSCLC?

“Oxnard: Combination BRAF/MEK inhibitor therapy is a very compelling approach because combinations of BRAF and MEK inhibitors have clearly been shown to improve response rates and overall survival in melanomas harboring BRAF V600E mutations when compared with single-agent BRAF inhibition.”

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.


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.’ ”

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.


Combining BRAF Inhibition, Anti-PD-1 No Help in BRAF-Mutant Melanoma

Excerpt:

“Patients with BRAF-mutant melanoma obtained no survival benefit from combined treatment of anti-BRAF therapy and an immune checkpoint inhibitor, a retrospective analysis showed.

“Median progression-free survival (PFS) was 6.0 to 6.5 months in BRAF-inhibitor naive patients who received a PD-1/PD-L1 inhibitor alone or with a BRAF inhibitor. Patients with prior exposure to a BRAF inhibitor had a median PFS of 8.0 months with anti–PD-1 therapy and 4.5 months with combined treatment. Median overall survival was 10.5 to 12 months with a PD-1/PD-L1 inhibitor alone or in combination with a BRAF inhibitor, regardless of prior BRAF inhibitor exposure status.

“ ‘BRAF inhibitor-refractory patients derived no additional benefit with anti-PD therapy in combination with BRAF inhibition,’ Wen-Jen Hwu, MD, of MD Anderson Cancer Center in Houston, and colleagues concluded in a poster presentation at the 2016 ASCO Annual Meeting in Chicago. ‘Clinical findings are similar with either anti-PD alone or in combination with BRAF inhibition in terms of objective response rate (ORR), disease control rate (DCR), and overall survival (OS).’ ”

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.


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.


Distinct Features Associated With Benefit for BRAF/MEK Inhibition

Excerpt:

“With the development of novel targeted and immunotherapeutic agents that are more efficacious than traditional chemotherapy, treatment paradigms in melanoma have undergone major changes. Current recommendations for first-line systemic therapy for patients with advanced or metastatic melanoma consider BRAF mutation status, tumor growth rate, and the presence or absence of cancer-related symptoms.

“Immunotherapies with agents that block CTLA-4 or PD-1/PD-L1 checkpoints have been associated with durable responses in a subset of patients, and are often considered for patients with low-volume, asymptomatic metastatic melanoma. Targeted therapies, on the other side, are preferred for patients with BRAF-mutant tumors who have symptomatic disease and benefit from the rapid response associated with these agents.”

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.


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.”

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.