Neoadjuvant Osimertinib With/Without Chemotherapy Versus Chemotherapy Alone for EGFR-Mutated Resectable Non-Small-Cell Lung Cancer: NeoADAURA

Abstract

Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II–IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed.

Trial Registration number: NCT04351555 (ClinicalTrials.gov)

Lay abstract

A plain language version of this article is available and is published alongside the paper online: www.tandfonline.com/doi/suppl/10.2217/fon-2021-0549

Keywords:

• EGFR-TKI-sensitizing mutations
• EGFR-tyrosine kinase inhibitor
• neoadjuvant
• non-small-cell lung cancer
• osimertinib
• resectable

Author contributions

Conception and design: S Dacic, C Blakely, C Escriu, A Walding and JE Chaft. Drafting the manuscript: all authors. Manuscript writing: A Walding, JE Chaft. Final approval of the manuscript: all authors. Agree to be accountable for all aspects of the work, which includes ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors.

Acknowledgments

Thanks to all the patients and their families.

Financial & competing interests disclosure

This trial (NCT04351555) was funded by AstraZeneca, the manufacturer of osimertinib. The funder contributed to the conception and design of the trial; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication and as such are included in the author list and acknowledgments. M Tsuboi – advisory boards: AstraZeneca, MSD, Novartis; honoraria received from promotional activities: AstraZeneca KK, Bristol-Myers Squibb KK, Chugai Pharmaceutical Co Ltd, Eli Lilly Japan, Johnson & Johnson Japan, Medtronic Japan, Ono Pharmaceutical Co Ltd, Taiho Pharma, Teijin Pharma. W Weder – consultant: AstraZeneca, Medtronic. C Escriu – speakers bureau: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Pfizer; advisory boards: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD. C Blakely – advisory board: Blueprint Medicines, Bayer; consultant: Amgen. J He – nothing to disclose. S Dacic – advisory board: AstraZeneca, Takeda, Janssen; consultant: AstraZeneca. Y Yatabe – advisory boards: AstraZeneca, Daiichi-Sankyo, MSD, Amgen, Takeda; honoraria received from promotional activities: Alilent/Dako, AstraZeneca, Chugai Pharma, MDS, Novartis, Pfizer, Roche/Ventana, Thermo Fisher Scientific. L Zeng – ownership or stock interests: AstraZeneca; employment: AstraZeneca. A Walding – ownership or stock interests: AstraZeneca; employment: AstraZeneca. JE Chaft – consultant: AstraZeneca, Flame Biosciences, Genentech, Merck, Novartis, Jannsen. Cancer Center Support Grant P30 CA00874. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors would like to acknowledge S Cotterill of Ashfield MedComms, an Ashfield Health company, and C McCleverty contracted to Ashfield MedComms, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Ethical conduct of research

The study will be conducted in accordance with the consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines and applicable International Conference on Harmonization Good Clinical Practice Guidelines.

Data-sharing statement

Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca's data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Additional information

Funding

This trial (NCT04351555) was funded by AstraZeneca, the manufacturer of osimertinib. The funder contributed to the conception and design of the trial; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication and as such are included in the author list and acknowledgments. M Tsuboi – advisory boards: AstraZeneca, MSD, Novartis; honoraria received from promotional activities: AstraZeneca KK, Bristol-Myers Squibb KK, Chugai Pharmaceutical Co Ltd, Eli Lilly Japan, Johnson & Johnson Japan, Medtronic Japan, Ono Pharmaceutical Co Ltd, Taiho Pharma, Teijin Pharma. W Weder – consultant: AstraZeneca, Medtronic. C Escriu – speakers bureau: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Pfizer; advisory boards: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD. C Blakely – advisory board: Blueprint Medicines, Bayer; consultant: Amgen. J He – nothing to disclose. S Dacic – advisory board: AstraZeneca, Takeda, Janssen; consultant: AstraZeneca. Y Yatabe – advisory boards: AstraZeneca, Daiichi-Sankyo, MSD, Amgen, Takeda; honoraria received from promotional activities: Alilent/Dako, AstraZeneca, Chugai Pharma, MDS, Novartis, Pfizer, Roche/Ventana, Thermo Fisher Scientific. L Zeng – ownership or stock interests: AstraZeneca; employment: AstraZeneca. A Walding – ownership or stock interests: AstraZeneca; employment: AstraZeneca. JE Chaft – consultant: AstraZeneca, Flame Biosciences, Genentech, Merck, Novartis, Jannsen. Cancer Center Support Grant P30 CA00874. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed