High-Throughput Genomics May Improve Outcomes in Difficult-to-Treat Cancers

Key Points

  • High-throughput genomics may improve outcomes in a subset of patients with difficult-to-treat cancers.
  • Following targeted therapy, of the evaluable patients, 2 had complete responses and 20 had partial responses, for an overall response rate of 11%; 100 patients had stable disease and 33 had progressive disease. Median overall survival was 11.9 months.

A study investigating the hypothesis that testing a large number of genes across all cancer tumor types could improve outcomes for patients with difficult-to-treat cancers by using targeted therapies has found that progression-free survival was significantly higher in the those treated with targeted therapies than in those treated with a previous line of therapy. However, the study authors cautioned that randomized trials are needed to validate their findings and quantify the magnitude of benefit. The study by Massard et al was published in Cancer Discovery.

Study Methodology

The researchers launched the Molecular Screening for Cancer Treatment Optimization (MOSCATO 01) trial to test whether high-throughout analyses may improve outcomes in patients with advanced cancers. The primary objective of the study was to evaluate clinical benefits as measured by the percentage of patients presenting progression-free survival on matched therapy (PFS2) 1.3-fold longer than progression-free survival on prior therapy (PFS1).

Between 2011 and 2016, the researchers enrolled 1,035 adults with advanced, unresectable, or metastatic cancer that had progressed after at least one prior therapy. A biopsy was performed on 948 patients, and the researchers analyzed tissue by array comparative genomic hybridization, next-generation sequencing, and RNA sequencing on 843 patients.

The most frequent tumor types were of the digestive tract, lung, urologic system, breast, and head and neck. The most frequent alterations in these tumors were observed in the genes of PIK3CA, ERBB2, PTEN, FGFR1, EGFR, and NOTCH.

Study Results

The researchers identified an actionable molecular alteration in 411 of the 843 patients with a molecular portrait. A total of 199 patients were treated with a targeted therapy matched to a genomic alteration. The PFS2/PFS1 ratio was > 1.3 in 33% of the patients (63/193).

Objective responses were observed in 22 of 194 patients (11%; 95% confidence interval [CI], 7%–17%), and median overall survival was 11.9 months (95% CI, 9.5–14.3 months).

Study Significance

“This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers. Although these results are encouraging, only 7% of the successfully screened patients benefited from this approach. Randomized trials are needed to validate this hypothesis and to quantify the magnitude of benefit. Expanding drug access could increase the percentage of patients who benefit,” concluded the study authors.

Fabrice André, MD, PhD, of the Institut Gustave Roussy, is the corresponding author of this study.

Funding for this study was provided by the Foundation Gustave Roussy, Genentech, and Sanofi.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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