A subset of lung cancer patients can derive important clinical benefits from drugs that are more commonly used to treat melanoma, the authors of a new academic clinical trial in Europe have reported at the European Lung Cancer Conference (ELCC) in Geneva, Switzerland.
Oliver Gautschi, MD, a medical oncologist from Lucern Cantonal Hospital in Switzerland, presented the results of the retrospective EURAF cohort study, which included patients with lung cancer whose tumors carried specific mutations in the BRAF gene. A network of European oncologists, without company involvement, conducted the study.
BRAF mutations are commonly seen in melanoma patients, and are found in approximately 2% of lung adenocarcinomas, Gautschi explained. 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.
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“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 said.
The EURAF study gathered information on 35 patients with lung cancer, identified as carrying BRAF mutations, were treated with B-Raf inhibitors between 2012 and 2014.
Most of those patients received vemurafenib, some received dabrafenib, and one received 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 enrollment in a clinical trial. The researchers said this means that these results are encouraging, 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,” said Gautschi.
Commenting on the findings, David Planchard, MD, PhD, pulmonary oncologist at Gustave Roussy in Villejuif, France, said 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.
“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 noted that this combination has shown a higher clinical benefit in BRAF-mutant melanoma.
