Found 1 Presentation For Request "122P"
122P - Osimertinib as first-line (1L) treatment for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC): Final efficacy and safety results from two phase I expansion cohorts
- J. Yang (Taipei city, Taiwan)
- J. Yang (Taipei city, Taiwan)
- S. Ramalingam (Atlanta, United States of America)
- C. Lee (Kogarah, NSW, Australia)
- T. Kurata (Osaka, Japan)
- D. Kim (Seoul, Korea, Republic of)
- T. John (Heidelberg, Australia)
- N. Nogami (Matsuyama, Japan)
- Y. Ohe (Tokyo, Japan)
- Y. Rukazenkov (Macclesfield, Cheshire, United Kingdom)
- M. Murphy (Cambridge, United Kingdom)
- P. Jänne (Boston, MA, United States of America)
Abstract
Background
Osimertinib is a 3rd-generation, CNS-active EGFR-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M resistance mutations. Earlier results from the Ph I AURA (NCT01802632) and Ph III FLAURA (NCT02296125) studies have established 1L osimertinib efficacy. We report final efficacy and safety data from two Ph I expansion cohorts who received 1L osimertinib 80 or 160 mg for advanced EGFRm NSCLC in AURA.
Methods
Treatment-naïve pts with locally advanced/metastatic EGFRm NSCLC received osimertinib 80 or 160 mg once daily. Endpoints included objective response rate (ORR), progression-free survival (PFS) and safety evaluation. EGFRm status was confirmed via local and/or central laboratory testing. Key eligibility criteria included measurable disease and WHO performance status 0/1. Pts with stable asymptomatic CNS metastases were eligible. Data cutoff: 1 May 2018.
Results
Overall, 60 patients (pts) were enrolled at two doses (80 mg, n = 30; 160 mg, n = 30): 75% female; 72% Asian; 43% with EGFR ex19del; 48% with L858R. Five pts were EGFR T790M mutation-positive by central test at study entry. Median follow up: 19.1 mo. ORR (95% CI): 67% (47, 83) in the 80 mg cohort, 87% (69, 96) in the 160 mg cohort, 77% (64, 87) overall. Median duration of response (95% CI): 19.3 mo (12.2, 24.7) in the 80 mg cohort, 16.7 mo (9.7, 29.0) in the 160 mg cohort, 18.0 mo (12.5, 24.7) overall. Median PFS (95% CI): 22.1 mo (12.3, 30.2) in the 80 mg cohort, 19.3 mo (11.1, 26.0) in the 160 mg cohort, 20.5 mo (13.7, 26.1) overall (78% maturity). 42% (95% CI 29, 54) and 14% (95% CI 6, 26) of pts were progression free at 24 and 48 mo, respectively. Dose reductions occurred in 27% and 60% of pts at 80 mg and 160 mg, respectively. Most common adverse events overall: (% [Grade ≥3]) diarrhoea (80 mg, 63% [3%]; 160 mg, 87% [7%]), stomatitis (80 mg, 47% [0]; 160 mg, 53% [3%]), paronychia (80 mg, 37% [0]; 160 mg, 57% [10%]).
Conclusions
Consistent with previously reported results, 1L osimertinib for EGFRm advanced NSCLC results in prolonged PFS at both doses and better tolerability at the 80 mg dose.
Clinical trial identification
NCT01802632 (25 February 2013).
Editorial acknowledgement
Medical writing support was provided by Natasha Cary BSc, from iMed Comms, an Ashfield Company and funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
J.C-H. Yang: Honoraria: BI, Roche, MSD, AstraZeneca, Novartis; Consulting/advisory: BI, Novartis, AstraZeneca, Roche/Genentech, Clovis Oncology, Lilly, MSD, Merck Serono, Celgene, Astellas Pharma, Bayer, Pfizer, Ono Pharmaceutical, Bristol-Myers Squibb, Yuhan, Hansoh. S.S. Ramalingam: Advisory boards: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, Lilly, Merck, Roche, Nektar, Loxo, Takeda; Research grants: Merck, Tesaro. C.K. Lee: Advisory boards: AstraZeneca, Roche, Norvatis, Pfizer. Research funding to institution: AstraZeneca for the trials in which I am currently involved. T. Kurata: Research grants: AstraZeneca, MSD; Honoraria: AstraZeneca, MSD, Ono, Bristol-Myers Squibb, Chugai, Eli Lilly. D-W. Kim: Advisory board membership, personal expenses: Novartis. T. John: Consultancy: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, Pfizer, Novartis, Merck, Roche. N. Nogami: Honoraria: AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan K.K., MSD, ONO Pharmaceutical, Pfizer Japan Inc., Taiho Pharmaceutical. Y. Ohe: Honoraria, consulting, research funding: AstraZeneca, Chugai, Dainippon Lilly, Ono, BMS Japan, Daiichi Sankyo, BI, Bayer, Ignyta, Pfizer, MSD, Taiho, Novartis, Kyorin, Kyowa Hakko Kirin, Takeda, Celltrion. Y. Rukazenkov: Employee and shareholder: AstraZeneca. P.A. Jänne: Consultancy: AstraZeneca, BI, Pfizer, Merrimack, Roche/Genentech, Chugai, AceaBiosciences, ARIAD Pharma, Ignyta, LOXO Oncology; Stock ownership: Gatekeeper Pharma; Research funding: Astellas, AstraZeneca; IP: EGFR mutations licensed to Lab Corp. All other authors have declared no conflicts of interest.