One of the major advances in the management of metastatic non-small cell lung cancer over the last few years has been the identification of tumour alterations that can be targeted for therapeutic benefit. These include mutations, translocations in genes such as ALK or ROS1 and now tumour PD-L1 expression that defines the use of immunotherapy. These tumour alterations are primarily detected based on tissue-based assays. However, these tissue-based assays do have their limitations in that in about 30% of the patients the tumour tissue obtained at the time of diagnostic biopsy is inadequate to perform all the necessary assays. In addition, particularly in lung cancer, repeat biopsies may not be feasible and even if repeat biopsies are conducted, tissue biopsy obtained at the time of second biopsy also may not be adequate to perform tissue-based assays. Potentially blood-based NGS testing could overcome some of these limitations.
BFAST is the first prospective phase II/III global study that is using a blood-based NGS assay as a standalone test to identify actionable genetic alterations and assign advanced non-small cell lung cancer patients to appropriate targeted therapy or immunotherapy. One of the cohorts in this study was the ALK positive cohort and the results of that cohort is what I’m going to be presenting at this meeting.
The overall goal of the ALK cohort was to demonstrate that the clinical efficacy of an ALK targeting drug such as alectinib is consistent in this study or in this patient population, which was defined to have ALK translocation based on a blood-based NGS assay, as compared to the clinical efficacy of alectinib demonstrated in the global ALEX trial in which patients were identified to have ALK translocation based on a tissue-based assay. So the overall goal was to show that there is consistency and if we were able to demonstrate that then one could say that blood-based NGS testing could be used in the management of advanced ALK positive non-small cell lung cancer patients.
We screened 2,219 patients and of these 119 were found to have ALK translocations in their tumour based on this blood-based NGS assay. That rate of about 5.4% is what one would expect of about 5% ALK positive lung cancer in this patient population. Of those, 87 patients were actually enrolled on the study and the primary objective was confirmed response rate as assessed by investigators when treated with alectinib, an ALK inhibitor. The confirmed response rate was 87.4% and, as I mentioned, the goal was to ensure that there was a consistency in the efficacy of alectinib. So when you compare that to the confirmed response rate of alectinib in the global ALEX trial it was 71.7%, so very similar.
What was interesting is that only 1% of the patients had progression as their best response as opposed to 11% of the patients having progression as their best response in the global ALEX trial with alectinib. The median progression free survival had not been reached since the median follow-up is only 12.58 months. But the one year progression free survival with alectinib in this cohort was 78.38% and it was 68% with alectinib in the ALEX trial. The safety profiles were very similar to what has been reported with alectinib.
So our conclusions were that the primary objective was reached in this ALK cohort of the BFAST trial. These results do demonstrate the clinical utility of blood-based NGS testing in informing clinical decision making for the management of advanced ALK positive non-small cell lung cancer patients.