Dr. Oliver Gautschi, a medical oncologist from Lucern Cantonal Hospital in Switzerland, presented the results of the retrospective EURAF cohort study, which included lung cancer patients whose tumours carried specific mutations in the BRAF gene. The study was conducted by a network of European oncologists, without company involvement.
BRAF mutations are commonly seen in melanoma patients, and are found in about 2% of lung adenocarcinomas, Gautschi explains. Several inhibitors of the B-Raf protein, including vemurafenib and dabrafenib, have been developed for use in melanoma patients, however there is currently no approved drug for BRAF-mutant lung cancer.
As a result, experience with B-Raf inhibitors in lung cancer remains limited. “In the current study, we wanted to find out how many patients in Europe received B-Raf inhibitors outside of a clinical trial, and what their outcomes were,” Gautschi says.
The EURAF study gathered information on 35 lung cancer patients who had been identified as carrying BRAF mutations, who were treated with B-Raf inhibitors between 2012 and 2014.
Most of those patients received vemurafenib, some dabrafenib, and one sorafenib. Overall response rate was 53% as measured by the widely used Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. Overall, progression-free survival time in this group was 5 months.
Most patients were pretreated, and not eligible for enrolment in a clinical trial, which means these results are encouraging, the researchers say, although the study’s small size and retrospective nature mean the analysis of the magnitude of benefit should be treated cautiously.
“The bottom line is that clinicians should be sure to test patients for so-called ‘rare’ driver mutations in lung cancer, because individual patients may derive substantial benefit from targeted therapy,” says Gautschi.
Commenting on the findings, Dr David Planchard, pulmonary oncologist at Gustave Roussy in Villejuif, France, said that the results of the trial confirm the benefit of B-Raf inhibitors in BRAF-mutant non-small cell lung cancer. The current trial also confirmed the good tolerance of the drugs with no new side-effects, he said. Planchard and colleagues have presented a separate phase II study in this area with dabrafenib.
“This trial is important because due to the low frequency of this mutation in non-small cell lung cancer we will have few trials on this population,” Planchard commented. “The more data we have, the better we understand how important it is to test for the mutation, especially in adenocarcinomas, and to expose mutation-positive patients to a specific B-Raf inhibitor.”
The results also add to growing support for the approval of B-Raf inhibitors for use in lung cancer, Planchard added. This is important because the rarity of this mutation means that performing the kind of randomized phase III trials usually required for licensing approval will be extremely difficult, he noted.
Looking ahead, it will also be important to see results of combination therapy with inhibitors of B-Raf and a related protein, Mek, in non-small cell lung cancer carrying BRAF-V600E mutations, the researchers note, as this combination has shown a higher clinical benefit in BRAF-mutant melanoma.