Studies show drug combinations effective for melanoma

September 29, 2012

Promising new data on drug combinations to treat metastatic melanoma are presented at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.

The phase I and II trials focus on combining drugs to slow the development of resistance to drugs that inhibit BRAF, a gene that is mutated in about half of melanomas. Earlier trials with drugs that target BRAF generated excitement for their ability to quickly shrink tumors in suitable patients. But for many patients the benefits proved short-lived, as the develop resistance to the drugs.

"These studies exemplify an important landmark of some tumors, which has emerged from recent laboratory research: the presence of specific mutations, such as the BRAF mutation in which exposes an Achilles' heel—MEK in this case," said Prof Yossef Yarden from the Weizmann Institute of Science, Israel. "In-depth understanding of cancers and their mutations is expected to reveal more of these deadly weaknesses in cancer, which we can exploit using new drugs and ."

Phase II of the BRAF inhibitor dabrafenib alone vs combination with MEK1/2 inhibitor trametinib

Dr Georgina Long from Westmead Hospital and the Melanoma Institute Australia and colleagues report that combining the dabrafenib and trametinib provided a clinically meaningful improvement in progression-free survival, response rate and duration of response in 162 patients with melanoma that had BRAF V600 .

Patients in the study received either dabrafenib 150mg twice daily; twice-daily dabrafenib plus once-daily 1mg trametinib; or twice daily dabrafenib plus once-daily 2mg trametinib. The combination prolonged progresion free survival over single-drug therapy from 5.8 months to 9.4 months, which represents a 60% improvement. Among patients who received both drugs at the higher dose, 41% had not progressed 12 months after treatment began, compared to 9% in the monotherapy arm of the study.

"The combination therapy of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib prolongs the progression-free survival in patients with V600 BRAF mutation-positive metastatic melanoma compared with dabrafenic monotherapy," Dr Long said. "Importantly, the combination also decreases the rate of the cutaneous toxicities compared with dabrafenib monotherapy, particularly the oncogenic cutaneous toxicity of squamous cell carcinoma."

Phase IB study of vemurafenib in combination with the MEK inhibitor, GDC-0973

A Phase I study in 44 patients shows that the combination of the MEK inhibitor GDC-0973 and vemurafenib can be delivered safely, Dr Rene Gonzalez of the University of Colorado Cancer Center, Denver, and colleagues report.

"BRAF inhibition has resulted in high response rates and improved survival in patients with BRAF mutated melanoma," Dr Gonzalez said. "One of several mechanisms of resistance has been reactivation of the MAPK pathway. Preclinical models show that combined inhibition of BRAF and MEK can delay the acqusition of resistance compared to BRAF inhibitor monotherapy. Inhibition of the pathway downstream from BRAF with the MEK inhibitor GDC-0973 could theoretically overcome or delay this resistance mechanism and improve outcomes."

The study was not designed to evalate efficacy. "While early data in a small number of patients did show tumor reduction, it would be premature to comment on efficacy based on these preliminary results and further research is warranted," Dr Gonzalez said.

Explore further: Combination of targeted treatment drugs delays resistance in melanoma patients

Related Stories

Combination of targeted treatment drugs delays resistance in melanoma patients

September 29, 2012
Combined treatment with two drugs targeting different points in the same growth-factor pathway delayed the development of treatment resistance in patients with BRAF-positive metastatic malignant melanoma. The results of a ...

ASCO: Dabrafenib/Trametinib active in metastatic melanoma

May 17, 2012
(HealthDay) -- For patients with V600 BRAF-mutant solid tumors, treatment with the oral BRAF inhibitor dabrafenib and the oral MEK 1/2 inhibitor trametinib is tolerated and has clinical activity in BRAF inhibitor-naive metastatic ...

Uncommon BRAF mutation in melanoma sensitive to MEK inhibitor drug therapy

July 16, 2012
An uncommon mutation of the BRAF gene in melanoma patients has been found to respond to MEK inhibitor drugs, providing a rationale for routine screening and therapy in melanoma patients who harbor the BRAF L597 mutation.

ASCO: Trametinib improves survival in metastatic melanoma

June 5, 2012
(HealthDay) -- For patients with metastatic melanoma with activating mutations in serine-threonine protein kinase B-RAF (BRAF), treatment with the oral selective MEK inhibitor trametinib is associated with improved progression-free ...

New drug, Vemurafenib, doubles survival of metastatic melanoma patients

March 1, 2012
A report published this week in the New England Journal of Medicine shows that the 50 percent of metastatic melanoma patients with a specific genetic mutation benefit from the drug Vemurafenib – increasing median survival ...

Research shows promising treatments against skin cancer

June 4, 2012
Two new experimental treatments against advanced melanoma have shown promise in keeping the deadly skin cancer at bay, according to research presented in the United States on Monday.

Recommended for you

MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer

September 25, 2017
A new magnetic resonance imaging (MRI) contrast agent being tested by researchers at Case Western Reserve University not only pinpoints breast cancers at early stages but differentiates between aggressive and slow-growing ...

Alternative splicing, an important mechanism for cancer

September 22, 2017
Cancer, which is one of the leading causes of death worldwide, arises from the disruption of essential mechanisms of the normal cell life cycle, such as replication control, DNA repair and cell death. Thanks to the advances ...

'Labyrinth' chip could help monitor aggressive cancer stem cells

September 21, 2017
Inspired by the Labyrinth of Greek mythology, a new chip etched with fluid channels sends blood samples through a hydrodynamic maze to separate out rare circulating cancer cells into a relatively clean stream for analysis. ...

Whole food diet may help prevent colon cancer, other chronic conditions

September 21, 2017
A diet that includes plenty of colorful vegetables and fruits may contain compounds that can stop colon cancer and inflammatory bowel diseases in pigs, according to an international team of researchers. Understanding how ...

Drug combination may improve impact of immunotherapy in head and neck cancer

September 21, 2017
Checkpoint inhibitor-based immunotherapy has been shown to be very effective in recurrent and metastatic head and neck cancer but only in a minority of patients. University of California San Diego School of Medicine researchers ...

New kinase detection method helps identify targets for developing cancer drugs

September 21, 2017
Purdue University researchers have developed a high-throughput method for matching kinases to the proteins they phosphorylate, speeding the ability to identify multiple potential cancer drug targets.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.