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The challenges in the regulatory processes should not be ignored either. Regulatory agencies in different
countries and geographic regions, such as US/North America, European Union, Japan, and other Asia-
Pacific countries, may have different degrees of acceptance of the tissue-agnostic approach. It is encouraging
that recently the regulatory authorities in the US (larotrectinib and entrectinib), EU (larotrectinib), and
Japan (entrectinib) all gave the green light to tissue-agnostic indication for NTRK fusions. However, the
comfort level of these agencies may be different if the next agent does not have the splendid response rates
larotrectinib and entrectinib exhibited, and the future approvals are likely to be reviewed on case-by-case
basis and no established playbook exists.

CONCLUSION
With the rapid advances in cancer genomics, drug design and precision diagnostics, the field of oncology
drug development has entered an era when both traditional tissue-restricted and innovative tissue-agnostic
approaches provide precedented approval paths. Despite the challenges, we anticipate that tissue-agnostic
approvals will continue to grow and expand the therapeutic options for cancer patients in need.

DECLARATIONS
Authors’ contributions
Researched and gathered the material and data: Li IW
Reviewed the manuscript: Li IW, Wei G, Li G
Drafted the manuscript: Krishnamurthy N, Wei G, Li G
Proposed the concept: Li G

Availability of data and materials
Not applicable.

Financial support and sponsorship
Li IW and Krishnamurthy N were supported by the Emperor Science Awards, an initiative of Stand Up To
Cancer (SU2C), made possible by support from Genentech, Bristol-Myers Squibb Company, and Novartis.

Conflicts of interest
Wei G and Li G are employees of QED Therapeutics and equity owners.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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