Presence of genetic mutation across several tumor types may help develop more precise anti-cancer therapies

• The phase II study, published in The New England Journal of Medicine, shows that the most common mutation of the BRAF protein (BRAFV600), responsible for sending signals inside cancer cells, also occurs in nonmelanoma cancers. This discovery could help to develop targeted and molecular therapies against these BRAF V600- mutated tumors.

• The study also evidences the efficacy of vemurafenib (an inhibitor of this mutation) as therapy against multiple tumor types that share the BRAFV600 mutation.

• While this mutation is present in 50% of melanoma skin cancers, this is the first time that its occurrence has been analyzed across non melanoma types (lung cancer, ovarian cancer, colorectal cancer, cholangiocarcinoma, breast cancer, and multiple myeloma).

• This study is the first example of the so-called ´basket trial´ design aimed at matching patients with a rare mutation, irrespective of tumor histology, to a therapy expected to work through the mutated pathway.

Barcelona, 20 August , 2015. An international, phase II study, published in The New England Journal of Medicine, analyzed the role of one of the most common mutations of the BRAF protein (BRAFV600), responsible for sending signals inside cancer cells, across several tumor types other than melanoma. Although it is known that this mutation is present in 50% of melanoma cancers, it has also now been identified in other tumors. This trial specifically studied the presence of the mutation in pulmonary adenocarcinoma, ovarian cancer, colorectal cancer, cholangiocarcinoma, breast cancer, multiple myeloma, Erdheim-Chester disease and Langerhans cell histiocytosis. This finding will, in subsequent trials, facilitate the design of targeted molecular therapies against this mutation to improve the efficacy of current treatments.

This basket trial enrolled 122 patients who had different types of cancer with the BRAFV600 mutation. Recruited from 23 hospitals across the globe, 89% of these patients had received at least one line of treatment before participating in the study. Ninety-five of these patients received therapy with vemurafenib, the drug that has been shown to be effective in melanoma as an inhibitor of the BRAFV600 mutation, and 27 were treated with vemurafenib combined with cetuximab, an antibody that acts against the EGFR (epidermal growth factor receptor) protein. The results show that vemurafenib is effective across different tumor types, especially against pulmonary adenocarcinoma and Erdheim-Chester disease and Langerhans cell histiocytosis, where the response rates were 42% and 43% respectively. There were also responses, although lower, in ovarian cancer, cholangiocarcinoma, glioblastoma, thyroid cancer, and pancreatic cancer.

“This is the first broad trial that has been conducted to establish the presence of one of the most common mutations occurring in melanoma across other tumor types. The results enable us to extend the same therapy, which had already been shown to be effective as an inhibitor of this mutation in melanoma, to other different cancers, as well as more finely tune targeted therapy to the specificities of each patient,” says Josep Tabernero, Head of the Medical Oncology Department, the Vall d’Hebron University Hospital, Director of the Vall d´Hebron University Hospital, and one of the study’s principal investigators.

The basket trial design of this study maximizes the possibility of simultaneously detecting early signs of activity across multiple tumor types. The detection of these alterations in tumors act as biomarkers to refine treatment and targeted therapies in order to put the brakes on disease progression. This is particularly important since tumors can mutate during the course of disease and therapies cease to be effective. These studies are therefore crucial in analyzing the biology of each tumor and the characteristics that it shares with others.

In a more advanced phase, the study of the efficacy of vemurafenib will need to be further explored in these other nonmelanoma tumor types since its therapeutic potential is often difficult to analyze through specific studies due to the large number of tumor types involved, the low frequency of BRAFV600 mutations, and the rarity of some tumor types.

Study reference: Vemurafenib in Multiple Nonmelanoma BRAFV600-Mutated Cancers


David M. Hyman, M.D., Igor Puzanov, M.D., Vivek Subbiah, M.D., Jason E. Faris, M.D., Ian Chau, M.D., Jean-Yves Blay, M.D., Ph.D., Jürgen S. Wolf, M.D., Ph.D., Noopur S. Raje, M.D., Eli L. Diamond, M.D., Antoine Hollebecque, M.D., Radj Gervais, M.D., Maria Elena Elez-Fernandez, M.D., Antoine Italiano, M.D., Ph.D., Ralf-Dieter Hofheinz, M.D., Manuel Hidalgo, M.D., Ph.D., Emily Chan, M.D., Ph.D., Martin Schuler, M.D., Susan Frances Lasserre, M.Sc., Martina Makrutzki, M.D., Florin Sirzen, M.D., Ph.D., Maria Luisa Veronese, M.D., Josep Tabernero, M.D., Ph.D., and Jose Baselga, M.D., Ph.D.


For more information please contact Amanda Wren, Director of Communication, the Vall d´Hebron Institute of Oncology (VHIO),, Tel: +34 695207886.

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