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Real-world data of off-label drug use in patients with actionable genomic alterations on next-generation sequencing

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Summary

Introduction We analyzed the outcomes of patients with advanced cancers in our institution treated with off-label drugs targeting actionable genomic alteration based on next-generation sequencing who did not qualify for clinical trials. Purposes Our study endpoint was objective tumor response or stable disease at 16 weeks or later after treatment initiation. Methods Sixteen patients were included, 8 treated with immune checkpoint inhibitors targeting PD-L1 expression or TP53 mutations and 8 with other drugs. Tumors were analyzed based on PD-L1 expression, TP53 mutation, MSI, TMB, MMR status, and other targetable alterations. Results Of the 16 patients in the intention-to-treat group, no patients had an objective response after 16 weeks. Eleven patients met the primary study endpoint with stable disease, 8 in the immune checkpoint inhibitors group and 3 in the non-immune checkpoint inhibitors group. Using the log-rank test, the p-value for the difference between groups was 0.008. Conclusions In this study with off-label drugs, immune checkpoint inhibitors targeting TP53 mutations or PD-L1 expression were superior to the other drugs. This suggests the possibility of off-label use of anti-cancer drugs based on next-generation sequencing to be beneficial for advanced cancer patients without other therapeutic options. 

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Data availability

We conducted an observational retrospective study. The datasets generated and analyzed were gathered from the EPIC database of the Mays Cancer Center, University of Texas Health MD Anderson Cancer Center and are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Mays Cancer Center, University of Texas Health San Antonio MD Anderson Cancer Center, Texas, USA

    Gabriel Roman Souza, Ahmed Abdalla, Sukeshi Arora & Daruka Mahadevan

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  1. Gabriel Roman Souza
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  2. Ahmed Abdalla
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  3. Sukeshi Arora
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  4. Daruka Mahadevan
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Contributions

Gabriel Roman Souza and Daruka Mahadevan contributed to the study conception and design. Material preparation and analysis were performed by Gabriel Roman Souza. Data collection was performed by all authors. The first draft of the manuscript was written by Gabriel Roman Souza and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gabriel Roman Souza.

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The institutional review board of the University of Texas Health San Antonio approved this study.

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This research involves human participants. This study was performed in line with the principles of the Declaration of Helsinki. The institutional review board of the University of Texas Health San Antonio approved this study.

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Roman Souza, G., Abdalla, A., Arora, S. et al. Real-world data of off-label drug use in patients with actionable genomic alterations on next-generation sequencing. Invest New Drugs 40, 643–649 (2022). https://doi.org/10.1007/s10637-022-01213-x

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  • DOI: https://doi.org/10.1007/s10637-022-01213-x

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