Abstract
To explore targeted treatment options in patients with non-small-cell lung cancer (NSCLC) with rare genetic mutations in the context of a patient-centric clinical trial, we initiated, in parallel, a phase 2 adaptive umbrella trial consisting of a criteria-fulfilled (CF) cohort and a compassionate use (CU) cohort under expanded eligibility criteria, and a prospective real-world study (RWS). Here, we present efficacy and safety data from 48 patients with treatment-naive, advanced HER2-mutant NSCLC treated with the pan-HER receptor tyrosine kinase inhibitor pyrotinib (CF and CU cohorts) or physician’s therapy of choice (RWS cohort). In the phase 2 trial CF cohort (n = 28), the primary endpoint was reached with an objective response rate of 35.7% after pyrotinib treatment. Secondary endpoints included disease control rate (89.3%), median progression-free survival (PFS) (7.3 months), median overall survival (OS) (14.3 months) and toxicity, which was acceptable, with grade 3 or 4 treatment-related adverse events occurring in three patients (10.7%). The phase 2 trial CU cohort (n = 12) showed an objective response rate of 16.7%, disease control rate of 83.4%, median PFS of 4.7 months and median OS of 14.2 months after pyrotinib treatment. The RWS cohort (n = 8) had no responses to physician’s therapy of choice, while median PFS and OS were 3.0 and 12.2 months, respectively. Phase 2 umbrella trial, clinicaltrials.gov identifier: NCT03574402. RWS, clinicaltrials.gov identifier: NCT03605602.
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For eligible studies, qualified researchers may request access to individual patient-level clinical data. The datasets generated and/or analyzed during the current study are not publicly available due to proprietary considerations. All data will be shared in aggregate form and can be requested once the article has been published, if there is not a reasonable likelihood of participant reidentification. Access to patient-level data can be requested by contacting the lead investigator Y.-L.W. (syylwu@live.cn), who will decide whether the data can be provided. Requests will be processed within 8 weeks.
Change history
27 July 2023
In the version of this article initially published, the Abstract did not list the ClinicalTrials.gov identifiers NCT03574402 and NCT03605602, which are now amended in the HTML and PDF versions of the article.
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Acknowledgements
This work was funded by the National Natural Science Foundation of China (grant no. 82202997, S.-Y.M.L.), Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (grant no. 2017B030314120, Y.-L.W.), Guangdong Provincial People’s Hospital Scientific Research Funds for Leading Medical Talents in Guangdong Province (no. KJ012019426, Y.-L.W.), National Natural Science Foundation of China (grant no. 82072562, Q.Z.) and the High-Level Hospital Construction Project (grant no. DFJH201810, Q.Z.). Medical writing assistance and figure processing for this manuscript were provided by W. Shi and H. Dong of Jiangsu Hengrui Pharmaceuticals.
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Y.-L.W., Q.Z. and S.-Y.M.L. conceived and designed the study. S.-Y.M.L., H.-Y.T., X.-W.W. and C.L. collected and assembled the data. Y.-L.W., Y.L., Q.Z., H.-Y.T., S.-Y.M.L. and H.-H.Y. carried out the data analysis. H.-H.Y. performed the statistical analysis. J.-J.Y., H.-J.C., X.-R.D., J.-W.C., Z.Z., C.-R.X., M.-Y.Z., Y.-S.L., Z.W., A.-N.L., Y.-L.S., Y.D., Y.C., R.M., B.-H.W. and S.-D.C. recruited the patients. All authors were involved in data interpretation and in the writing, revision and critical review of the manuscript. All authors approved the submitted version and are accountable for their contributions and the integrity of the work.
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Y.-L.W. reports getting honoraria from AstraZeneca, Lily, Roche, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol-Myers Squibb/China, Hengrui Pharmaceutical and BeiGene Beijing; consulting and advisory services for AstraZeneca, Roche and Takeda; and getting research funding from Roche, Boehringer Ingelheim, Pfizer and BMS. Q.Z. reports honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, MSD, Pfizer, Roche and Sanofi outside the submitted work. The remaining authors declare no competing interests.
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Supplementary Information
General Protocol for CTONG1702, sub-protocol of arm 7 of CTONG1702, general protocol of CTONG1705, statistical analysis of arm 7 of CTONG1702 and statistical analysis of CTONG1705.
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Liu, SY.M., Tu, HY., Wei, XW. et al. First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial. Nat Med 29, 2079–2086 (2023). https://doi.org/10.1038/s41591-023-02461-x
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DOI: https://doi.org/10.1038/s41591-023-02461-x
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