TY - JOUR
T1 - Osimertinib versus platinum–pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis
AU - Papadimitrakopoulou, V. A.
AU - Mok, T. S.
AU - Han, J. Y.
AU - Ahn, M. J.
AU - Delmonte, A.
AU - Ramalingam, S. S.
AU - Kim, S. W.
AU - Shepherd, F. A.
AU - Laskin, J.
AU - He, Y.
AU - Akamatsu, H.
AU - Theelen, W. S.M.E.
AU - Su, W. C.
AU - John, T.
AU - Sebastian, M.
AU - Mann, H.
AU - Miranda, M.
AU - Laus, G.
AU - Rukazenkov, Y.
AU - Wu, Y. L.
N1 - Funding Information:
The authors thank all patients and their families. The authors acknowledge Laura Crocker, BMedSci, of Ashfield Healthcare Communications, Macclesfield, UK, part of UDG Healthcare plc, for medical writing support that was funded by AstraZeneca in accordance with GPP3 guidelines ( http://www.ismpp.org/gpp3 ). 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 .
Funding Information:
This study ( NCT02151981 ) was funded by AstraZeneca (no grant numbers were applicable in the funding of this study).
Funding Information:
VAP has declared honorarium from F Hoffman-La Roche; advisory or consultancy fees from Nektar Therapeutics, Astra Zeneca Pharmaceuticals, Arrys Therapeutics, Merck & Co, LOXO Oncology, Araxes Pharma, F. Hoffman–LaRoche Ltd, Janssen Research Foundation, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly & Co, Novartis Pharmaceuticals Corp., Takeda Pharmaceuticals, AbbVie, TRM Oncology, Tesaro, Exelixis, Gritstone, Leeds Biolabs, IDEAYA, Bolt Therapeutics, and G2 Innovation; and research funding from Eli Lilly & Co, Novartis, Merck, Astra Zeneca Pharmaceuticals, F Hoffman-La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, and Incyte. TSM has declared honoraria from ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Blueprint Medicines Corporation, Bristol-Myers Squibb, Celgene, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate, Hengrui Therapeutics, Ignyta, Incyte Corporation, InMed Medical Communication, IQVIA, Janssen, Loxo Oncology, Merck Serono, MSD, MORE Health, Novartis, OncoGenex Pharmaceuticals, OrigiMed, PeerVoice, Pfizer, PrIME Oncology, Roche/Genentech, Sanofi-Aventis R&D, SFJ Pharmaceutical, Takeda Pharmaceuticals HK, Vertex Pharmaceuticals, and Yuhan Corporation; advisory or consultancy fees from ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Blueprint Medicines Corporation, Bristol-Myers Squibb, Celgene, Cirina, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate, GeneDecode, Hengrui Therapeutics, Ignyta, Incyte Corporation, InMed Medical Communication, IQVIA, Janssen, Loxo-Oncology, Merck Serono, MSD, MORE Health, Novartis, OncoGenex Pharmaceuticals, OrigiMed, PeerVoice, Pfizer, PrIME Oncology, Roche/Genentech, Sanofi-Aventis R&D, SFJ Pharmaceutical, Takeda Pharmaceuticals HK, Vertex Pharmaceuticals, and Yuhan Corporation; leadership roles for AstraZeneca and Hutchison Chi-Med; research funding from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, MSD, Novartis, Pfizer, Roche, SFJ, and Xcovery; shareholdings in Hutchison Chi-Med, and Sanomics; stock options in Clearbridge BioMedics (now Biolidics), Loxo-Oncology, OrigiMed, and Virtus Medical Group; and officer or director for AstraZeneca, Hutchison Chi-Med (remunerated), American Society of Clinical Oncology (ASCO), Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), and International Association for the Study of Lung Cancer (IASLC; term ended on 30/4/19 [non-remunerated]). J-YH has declared honoraria from Roche, AstraZeneca, Bristol-Myers Squibb, MSD, and Takeda; advisory or consultancy fees from AstraZeneca, Bristol-Myers Squibb, MSD, Takeda, Pfizer, Novartis, and Lilly; research funding from Roche, Pfizer, Ono Pharmaceutical, and Takeda. M-JA has declared advisory or consultancy fees from AstraZeneca, MSD, Ono Pharmaceutical, and Lilly; and speaker fees from AstraZeneca, MSD, Ono Pharmaceutical, Lilly, Roche, Alpha Pharmaceutical, and Takeda. SSR has declared honoraria from AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Roche/Genentech, Loxo, Nektar, and Tesaro; advisory or consultancy fees from AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Roche/Genentech, Loxo, Nektar, and Tesaro; and research funding from AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Tesaro, Advaxis, and Takeda. SWK has declared advisory or consultancy fees from AstraZeneca; and research funding from AstraZeneca. FAS has declared advisory or consultancy fees from AstraZeneca; research funding from AstraZeneca; and shareholdings in AstraZeneca. JL has declared honoraria from Roche, AstraZeneca, and Pfizer; and research funding from Roche, Boehringer Ingelheim, Pfizer, and AstraZeneca. HA has declared honoraria from AstraZeneca, Chugai, Pfizer, and Boehringer Ingelheim; and advisory or consultancy fees from AstraZeneca and Pfizer. W-CS has declared travel, accommodation, or expenses from Bristol-Myers Squibb and Boehringer Ingelheim. TJ has declared advisory or consultancy fees from Roche, Bristol-Myers Squibb, Merck, Ignyta, AstraZeneca, Takeda, Boehringer Ingelheim, and Pfizer. MS has declared honoraria from AstraZeneca, Pfizer, Roche, Boehringer Ingelheim, Novartis, Celgene, Takeda, Lilly, Bristol-Myers Squibb, and MSD; advisory or consultancy fees from AstraZeneca, Pfizer, Roche, Boehringer Ingelheim, Novartis, Celgene, Takeda, Lilly, Bristol-Myers Squibb, and MSD; and speaker fees from AstraZeneca, Pfizer, Roche, Boehringer Ingelheim, Novartis, Celgene, Takeda, Lilly, Bristol-Myers Squibb, and MSD. Y-LW has declared honoraria from AstraZeneca, Roche, Eli Lilly, Pfizer, MSD, Bristol-Myers Squibb, and Boehringer Ingelheim; advisory or consultancy fees from AstraZeneca and Roche; and research funding from AstraZeneca and Roche. HM, MM, GL, and YR are employees of and have shareholdings in AstraZeneca. AD, YH, and WSMET have declared no conflicts of interest.
Publisher Copyright:
© 2020 European Society for Medical Oncology
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - Background: In AURA3 (NCT02151981), osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly prolonged progression-free survival and improved response in patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC) and progression on prior EGFR-TKI treatment. We report the final AURA3 overall survival (OS) analysis. Patients and methods: Adult patients were randomized 2 : 1 to osimertinib (80 mg orally, once daily) or pemetrexed plus carboplatin/cisplatin (platinum–pemetrexed) intravenously, every 3 weeks (≤6 cycles). Patients could crossover to osimertinib on progression confirmed by blinded independent central review. OS and safety were secondary end points. Results: A total of 279 patients were randomly assigned to receive osimertinib and 140 to platinum–pemetrexed (136 received treatment). At data cut-off (DCO; 15 March 2019), 188 patients (67%) receiving osimertinib versus 93 (66%) receiving platinum–pemetrexed had died. The hazard ratio (HR) for OS was 0.87 [95% confidence interval (CI) 0.67–1.12; P = 0.277]; the median OS was 26.8 months (95% CI 23.5–31.5) versus 22.5 months (95% CI 20.2–28.8) for osimertinib and platinum–pemetrexed, respectively. The estimated 24- and 36-month survival was 55% versus 43% and 37% versus 30%, respectively. After crossover adjustment, there was an HR of 0.54 (95% CI 0.18–1.6). Time to first subsequent therapy or death showed a clinically meaningful advantage toward osimertinib (HR 0.21, 95% CI 0.16–0.28; P < 0.001). At DCO, 99/136 (73%) patients in the platinum–pemetrexed arm had crossed over to osimertinib, 66/99 (67%) of whom had died. The most common adverse events possibly related to study treatment were diarrhea (32%; grade ≥3, 1%) and rash (grouped term; 32%; grade ≥3, <1%) in the osimertinib arm, versus nausea (47%; grade ≥3, 3%) in the platinum–pemetrexed arm. Conclusions: In patients with T790M advanced NSCLC, no statistically significant benefit in OS was observed for osimertinib versus platinum–pemetrexed, which possibly reflects the high crossover rate of patients from platinum–pemetrexed to osimertinib. Clinical trials number: ClinicalTrials.gov NCT02151981; https://clinicaltrials.gov/ct2/show/NCT02151981.
AB - Background: In AURA3 (NCT02151981), osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly prolonged progression-free survival and improved response in patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC) and progression on prior EGFR-TKI treatment. We report the final AURA3 overall survival (OS) analysis. Patients and methods: Adult patients were randomized 2 : 1 to osimertinib (80 mg orally, once daily) or pemetrexed plus carboplatin/cisplatin (platinum–pemetrexed) intravenously, every 3 weeks (≤6 cycles). Patients could crossover to osimertinib on progression confirmed by blinded independent central review. OS and safety were secondary end points. Results: A total of 279 patients were randomly assigned to receive osimertinib and 140 to platinum–pemetrexed (136 received treatment). At data cut-off (DCO; 15 March 2019), 188 patients (67%) receiving osimertinib versus 93 (66%) receiving platinum–pemetrexed had died. The hazard ratio (HR) for OS was 0.87 [95% confidence interval (CI) 0.67–1.12; P = 0.277]; the median OS was 26.8 months (95% CI 23.5–31.5) versus 22.5 months (95% CI 20.2–28.8) for osimertinib and platinum–pemetrexed, respectively. The estimated 24- and 36-month survival was 55% versus 43% and 37% versus 30%, respectively. After crossover adjustment, there was an HR of 0.54 (95% CI 0.18–1.6). Time to first subsequent therapy or death showed a clinically meaningful advantage toward osimertinib (HR 0.21, 95% CI 0.16–0.28; P < 0.001). At DCO, 99/136 (73%) patients in the platinum–pemetrexed arm had crossed over to osimertinib, 66/99 (67%) of whom had died. The most common adverse events possibly related to study treatment were diarrhea (32%; grade ≥3, 1%) and rash (grouped term; 32%; grade ≥3, <1%) in the osimertinib arm, versus nausea (47%; grade ≥3, 3%) in the platinum–pemetrexed arm. Conclusions: In patients with T790M advanced NSCLC, no statistically significant benefit in OS was observed for osimertinib versus platinum–pemetrexed, which possibly reflects the high crossover rate of patients from platinum–pemetrexed to osimertinib. Clinical trials number: ClinicalTrials.gov NCT02151981; https://clinicaltrials.gov/ct2/show/NCT02151981.
KW - AURA3
KW - epidermal growth factor receptor-tyrosine kinase inhibitor
KW - non-small-cell lung cancer
KW - osimertinib
KW - overall survival
UR - http://www.scopus.com/inward/record.url?scp=85091610802&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091610802&partnerID=8YFLogxK
U2 - 10.1016/j.annonc.2020.08.2100
DO - 10.1016/j.annonc.2020.08.2100
M3 - Article
C2 - 32861806
AN - SCOPUS:85091610802
VL - 31
SP - 1536
EP - 1544
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 11
ER -