A real-world study of second or later-line osimertinib in patients with EGFR T790M-positive NSCLC: the final ASTRIS data

Abstract

Aim: Report the final analysis from ASTRIS, the largest real-world study of second-/later-line osimertinib in advanced/metastatic EGFR T790M non-small-cell lung cancer (NSCLC). Methods: Patients with advanced/metastatic EGFR T790M NSCLC and prior EGFR-TKI treatment, received once-daily osimertinib 80mg. Primary end point: overall survival (OS); secondary end points: progression-free survival (PFS), time-to-treatment discontinuation (TTD) and response rate. Safety was also recorded. Results: In 3014 patients, median OS: 22.8 months (21.6–23.8), median PFS: 11.1 months (11.0–12.0), median TTD: 13.5 months (12.6–13.9), and response rate: 57.3% (55.5–59.2). All end points reported with 95% CIs. Numerically longer median OS was observed in patients with baseline WHO performance status <2 versus 2 (24.0 vs 11.1 months) and those without versus with brain/leptomeningeal metastases (25.4 vs 18.0 months). No new safety signals were identified. Conclusion: Second-/later-line osimertinib demonstrated real-world clinical benefit and safety in advanced/metastatic EGFR T790M NSCLC.

Clinical Trial Registration: NCT02474355 (ClinicalTrials.gov)

Plain language summary

Osimertinib is a drug that blocks the activity of a protein called EGFR on cancer cells, reducing their growth and spread. ASTRIS is the largest real-world study that evaluated the outcomes with osimertinib treatment for patients with advanced non-small-cell lung cancer (NSCLC), and the EGFR T790M mutation, who had received previous treatment for their cancer. There were 3014 patients included in this study. The main aim of this study was to measure the time at which half of the patients were still alive after starting osimertinib treatment, this was 22.8 months. The study also measured the time at which half of the patients had experienced worsening (progression) of their cancer (11.1 months) and the time when half of the patients had stopped receiving osimertinib treatment (13.5 months). None of the patients experienced any unexpected side effects of the treatment. These data are consistent with those observed in comparable clinical trials with osimertinib, supporting the use of osimertinib treatment for patients with advanced NSCLC and the EGFR T790M mutation after their initial cancer treatment has stopped working.

Keywords::

• EGFR
• non-small-cell lung cancer
• osimertinib
• real world
• T790M

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2022-0919

Author contributions

P Cheema contributed to writing – review and editing. BB Cho contributed to data curation, investigation, resources, writing – original draft and writing – review and editing. H Freitas contributed to writing – review and editing. M Provencio contributed to conceptualization, methodology, supervision, validation, and writing – review and editing. Y-M Chen contributed to investigation, resources, supervision, and writing – review and editing. S-W Kim contributed to data curation, investigation, resources, and writing – review and editing. Y-L Wu contributed to conceptualization, investigation, writing – original draft, and writing – review and editing. A Passaro contributed to conceptualization, data curation, supervision, validation, and writing – review and editing. C Martin contributed to investigation and writing – review and editing. M Tiseo contributed to investigation, validation, and writing – review and editing. G-C Chang contributed to data curation, methodology, validation, and writing – review and editing. K Park contributed to conceptualization, data curation, formal analysis, investigation, methodology, resources, supervision, validation, writing – original draft, and writing – review and editing. B Solomon contributed to investigation and writing – review and editing. O Burghuber contributed to supervision, visualization, and writing – review and editing. J Laskin contributed to formal analysis, methodology, and writing – review and editing. Z Wang contributed to writing – review and editing. SY Lee contributed to resources, writing – original draft, and writing – review and editing. Y Hu contributed to supervision and writing – review and editing. J Vansteenkiste contributed to conceptualization, investigation, and writing – review and editing. H-L Zhang contributed to data curation and writing – review and editing. E Hanrahan contributed to data curation and writing – review and editing. T Geldart contributed to investigation, project administration, and writing – review and editing. R Taylor contributed to formal analysis and writing – review and editing. L Servidio contributed to conceptualization, formal analysis, funding acquisition, and writing – review and editing. J Li contributed to formal analysis, investigation, project administration, supervision, and writing – review and editing. FD Marinis contributed to conceptualization, methodology, supervision, and writing – original draft.

Acknowledgments

The authors would like to thank all the patients and their families.

Financial & competing interests disclosure

ASTRIS (NCT02474355) was funded by AstraZeneca, the manufacturer of the drug osimertinib. P Cheema has undertaken an advisory role on a council or committee with AstraZeneca, received honoraria from Amgen, BMS, Novartis, Roche, Pfizer, EMD Serono, Merck, Janssen, Bayer, BeiGene and has non-financial conflicts with AstraZeneca, BMS and Merck. BC Cho is an employee of Yonsei University College of Medicine, owns stock and shares with TheraCanVac Inc., Gencurix Inc., Bridgebio Therapeutics, KANAPH Therapeutic Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp., has undertaken an advisory role on a council or committee with KANAPH Therapeutics Inc., Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, Joseah BIO, is on the board of directors with Gencruix Inc., Interpark Bio Convergence Corp., has received consulting fees from Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono Pharmaceutical, Yuhan Corp., Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines, has received grants or funds from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan Corp., Ono Pharmaceutical, Dizal Pharma, MSD, AbbVie, MedPacto, GI Innovation Inc., Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp., has other potential financial relationships with Champions Oncology (Royalty), and has non-financial conflicts with DAAN Biotherapeutics (Founder). H Freitas has undertaken an advisory role on a council or committee (Steering committee) with AstraZeneca and advisory board with MSD, Pfizer, Eli Lilly, and Takeda, has received honoraria as a speaker from MSD, Roche, Eli Lilly, Pfizer, Takeda, BMS and Amgen, and has other potential financial relationships with PI/SI in studies sponsored by Roche, Pfizer, MSD, BMS, AstraZeneca, Janssen and Eli Lilly. M Provencio has undertaken an advisory role on a council or committee for BMS, AstraZeneca, MSD, Roche, and Takeda. Y-M Chen has undertaken an advisory role on a council or committee with Roche, AstraZeneca, Eli Lilly, Boehringer Ingelheim, MSD, Chugai, Ono Pharmaceuticals, BMS and has received consulting fees from Roche, AstraZeneca, Eli Lilly, Boehringer Ingelheim, MSD, Chugai, Ono Pharmaceuticals, and BMS. S-W Kim has received consulting fees from AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly, Roche, and BMS and grants or funds from AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly, and Yuhan Corp. Y-L Wu has undertaken an advisory role on a council or committee with AstraZeneca, Boehringer Ingelheim, Novartis, and Takeda, has received honorarium from AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi and grants or funds from AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Hengrui, and Roche. A Passaro reports no conflict of interest. C Martin has undertaken an advisory role on a council or committee with AstraZeneca and Pfizer. M Tiseo has received speakers’ and consultants’ fees from AstraZeneca, Pfizer, Eli Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Ostuka, Takeda, Pierre Fabre, Amgen, MSD, and Sanofi and has received institutional research grants from AstraZeneca and Boehringer Ingelheim. G-C Chang has received honoraria from Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, BMS, and MSD. K Park has undertaken an advisory role on a council or committee and grants or funds with AstraZeneca. B Solomon has undertaken an advisory role on a council or committee with Roche/Genentech, AstraZeneca, Pfizer, Novartis, BMS, Merck, Amgen, Takeda, BeiGene, and Eli Lilly and has received honoraria from Roche/Genentech, AstraZeneca, Pfizer, Novartis, BMS, Merck, Amgen, Takeda, BeiGene, and Eli Lilly. O Burghuber reports no conflict of interest. J Laskin has received honoraria from Roche, Pfizer, Eli Lilly, and Jazz Pharma. Z Wang reports no conflict of interest. SY Lee has received honoraria with AstraZeneca. Y Hu reports no conflict of interest. J Vansteenkiste has other potential financial relationships with AstraZeneca. H-L Zhang reports no conflict of interest. E Hanrahan has undertaken an advisory role on a council or committee with AstraZeneca and has received honoraria from AstraZeneca, Amgen, Roche, Takeda, BMS, and MSD. T Geldart reports no conflict of interest. R Taylor is an employee (contractor) with AstraZeneca. L Servidio is an employee and owns stock and shares with AstraZeneca. J Li is an employee and owns stock and shares with AstraZeneca. FD Marinis has undertaken an advisory role on a council or committee and has received consulting fees with Roche, BMS, AstraZeneca, and MSD. 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.

Writing assistance was provided by B Tynan, MSc, of Ashfield MedComms (Macclesfield, UK), part of UDG Healthcare 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 was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization (ICH)/GCP, applicable regulatory requirements and the AstraZeneca policy on Bioethics and Human Biological Samples. All patients provided informed written consent.

Data sharing statement

The authors certify that this manuscript reports the primary analysis of clinical trial data: NCT02474355. 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.