Celebrating the 10th Anniversary
A decade of discoveries in Cancer Discovery. For the community. By the Community.
Authors
Their impactful studies. In their words.
Gustave Roussy
Gustave Roussy
Gustave Roussy
This paper, among several other ones, has contributed to the implementation of next-generation sequencing in daily practice.
Q: What unanswered questions in the field was this study addressing?
A: The MOSCATO trial was first discussed at the end of 2010. At the time, we were describing the concept and feasibility of using high-throughput genomics for patient selection in genome-driven phase I/II trials, but we were facing two questions regarding the use of high-throughput genomics. The first one was its efficacy to drive patients to enrollment in phase I trials, and the second one was its clinical utility. Based on this background, we built MOSCATO, a single arm trial that evaluated the efficacy of multigene sequencing on progression-free survival (PFS). Because the trial tested both the capacity to select patients for phase I trials and the efficacy of sequencing, we could not perform a randomization and decided to assess the impact of tumor sequencing based on the comparison between PFS under genomic-matched therapy and the PFS under prior therapy.
Q: What surprised or excited you most about the findings?
A: We were first surprised by the high number of patients who could benefit from matched targeted therapy. Indeed, 23% of patients who had tumor sequencing could get access to a therapy matched to the genomic alteration. The most surprising finding was that more than 30% of patients derived benefit from a multigene sequencing. Some diseases like cholangiocarcinoma were associated with more efficacy. Finally, an important number of patients did not derive any benefit even though we thought a driver genomic alteration was identified.
Q: What has been the paper’s greatest impact in the years that followed?
A: This paper, among several other ones, has contributed to the implementation of next-generation sequencing in daily practice. This approach is now recommended in several diseases by scientific societies). More importantly, by showing that a large number of patients with an “actionable” alteration do not derive benefit from matched targeted therapy, this trial has highlighted the importance of the interpretation of the sequencing results. This led to the development of new tools that could rank genomic alterations according to their level of evidence, and, more importantly, to research programs on the modeling of cancer biology.
