Name:
Observational study of sequential afatinib and osimertinib in EGFR mutation-positive NSCLC: patients treated with a 40-mg starting dose of afatinib
Description:
Observational study of sequential afatinib and osimertinib in EGFR mutation-positive NSCLC: patients treated with a 40-mg starting dose of afatinib
Thumbnail URL:
https://cadmoremediastorage.blob.core.windows.net/2b96df8b-86ea-40a8-884f-81cebe600f76/videoscrubberimages/Scrubber_66.jpg
Duration:
T00H09M26S
Embed URL:
https://stream.cadmore.media/player/2b96df8b-86ea-40a8-884f-81cebe600f76
Content URL:
https://cadmoreoriginalmedia.blob.core.windows.net/2b96df8b-86ea-40a8-884f-81cebe600f76/Hochmair Presentation - FINAL.m4v?sv=2019-02-02&sr=c&sig=JyZyNbJkMsN7sF7%2BkkAnRwowbZzeVhcvdjV74f5OsSk%3D&st=2024-11-23T11%3A18%3A13Z&se=2024-11-23T13%3A23%3A13Z&sp=r
Upload Date:
2021-05-20T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
[MUSIC PLAYING]
SPEAKER 1: On behalf of Professor Maximilian J. Hochmair and his co-authors, this video summarizes the paper entitled "Observational Study of Sequential Afatinib and Osimertinib in EGFR Mutation-Positive NSCLC-- Patients Treated with a 40 milligrams Starting Dose of Afatinib," which was published in Advances in Therapy in February, 2020. The global observational GioTag study assessed outcomes in real world patients with EGFR mutation-positive NSCLC who received sequential afatinib and osimertinib.
SPEAKER 1: The objective of the post-hoc analysis reported here was to assess outcomes in patients who received the approved 40 milligram starting dose of afatinib as used in the clinical trial setting.
Segment:1 What was the purpose of this study?.
SPEAKER 1: [MUSIC PLAYING] Second and third-generation epidermal growth factor receptor tyrosine and kinase inhibitors have improved outcomes compared with first-generation EGFR-TKIs.
SPEAKER 1: However, regardless of the choice of therapy, acquired resistance to first-line EGFR-TKI treatment is inevitable, with 50% to 70% of patients who receive first-generation EGFR-TKIs or afatinib developing the T790M mutation. Osimertinib was developed specifically to target T790M and was initially approved for second-line use based on its efficacy in patients with tumors harboring this mutation.
SPEAKER 1: The choice of treatment after first-line osimertinib is less clear, as of resistance mechanisms to first-line osimertinib are heterogeneous, and not susceptible to current drugs. Thus, there is an argument for treating patients with sequential EGFR-TKI, reserving osimertinib as a second-line therapy to maximize the time on targeted therapy and delay the use of chemotherapy. To assess the benefit of sequential EGFR-TKI regiments, the non-interventional GioTag study was conducted in 204 patients with EGFR mutation-positive NSCLC with T790M acquired resistance who were treated with sequential afatinib and osimertinib in real world clinical practice.
SPEAKER 1: In the overall population, median time on treatment was 27.6 months, with particularly long treatment durations for Asian patients and those with the Del19 mutation. At the time of this initial analysis, overall survival data were immature, but a subsequent analysis found a median OS of 37.6 months. The overall GioTag study thus supported the strategy afatinib followed by osimertinib in patients with EGFR mutation-positive NSCLC who acquired T790M.
SPEAKER 1: This post-hoc analysis was conducted to determine the clinical benefit of sequential afatinib and osimertinib in the 169 patients who received the approved 40 milligram starting dose of afatinib as, has been used in the clinical trial setting. [MUSIC PLAYING]
Segment:2 How was the study undertaken?.
SPEAKER 1: The GioTag study was a global observational multi-center study that was conducted in 10 countries between December 2017 and May 2018.
SPEAKER 1: We retrospectively reviewed medical and electronic health records of patients with EGFR mutation-positive TKI-Naive advanced NSCLC who received first-line afatinib and subsequently developed the T790 mutation before starting osimertinib. The primary outcome was time on treatment, which was defined as the time from the first dose of afatinib to the last dose of osimertinib or death. In the present post-hoc analysis, we gathered data from the first full analysis, which had a database lock of June 2018.
SPEAKER 1: [MUSIC PLAYING]
Segment:3 What were the results?.
SPEAKER 1: For just the 169 patients who received the approved 40 milligram afatinib starting dose, baseline characteristics in the 40 milligram starters were similar to those in the overall population. Disease characteristics were also similar in the 40 milligram starters as in the overall group, with 73% of patients having the Del19 mutation, 10% having brain metastases, and 17% having ECOG performance status of greater than or equal to 2 at baseline.
SPEAKER 1: The main reason for discontinuation of afatinib and osimertinib was progressive disease, with 94% discontinuing afatinib and 75% discontinuing osimertinib for this reason. At the time of the database lock, 87 patients had discontinued osimertinib and 82 remained on treatment. For the subgroup analysis, we had a median follow up of 28.2 months, ranging from 14 to 97 months.
SPEAKER 1: The median time on treatment for sequential afatinib
SPEAKER 1: and osimertinib was 27.6 months, with a median time on afatinib of 11.5 months and a median time on osimertinib of 14.6 months. Clinical benefit with sequential afatinib and osimertibib was observed across all patient subgroups, and there was a particularly prolonged median time on treatment in Asian patients. In these patients, the overall time on treatment was 46.7 months, with a median 40.0 months on afatinib and 19.6 months on osimertinib.
SPEAKER 1: Median times on sequential and individual EGFR-TKI treatments were numerically longer in patients with a Del19 mutation compared with the L858R mutation, with an overall time on treatment of 29.9 versus 18.8 months. Median time on treatment was also longer in patients who had an ECOG performant status of 0 or 1 compared with 2, with an overall time on treatment of 31.3 versus 20.9 months.
SPEAKER 1: Importantly for real world clinical practice, clinical benefit was also seen in older patients and those with brain metastases, with median times on treatment of 27.6 months for those aged at least 65 years and 22.2 months for those with brain metastases. At the time of this analysis, overall survival data were immature, so we were limited to 2 and 2.5 year landmarks for the 40 milligram starters, where maturity was 45% and 35% respectively.
SPEAKER 1: The two-year OS rate from the start of afatinib treatment
SPEAKER 1: was 80%, and the 2.5 year OS rate was 70%.
Segment:4 What is the significance of these findings?.
SPEAKER 1: In this post-hoc analysis of the GioTag study, the median time on treatment with sequential afatinib and osimatinib in patients receiving a starting dose of 40 milligram afatinib of 27.6 months was consistent with that seen of the overall GioTag population. The median times for individual afatinib and osimatinib treatments were also consistent in this analysis and the overall study.
SPEAKER 1: The particular benefit in patients with Del19-positive disease versus those with L858R-positive disease was also seen in the overall GioTag population and has previously been seen in the phase three LUX-Lung three and six studies. The benefit with sequential afatinib and osimertinib treatment in Del19-positive patients is particularly relevant because Del19-positive tumors are more likely to acquire the T790M mutation.
SPEAKER 1: Importantly for real world clinical practice, we found that patients with characteristics associated with a poor prognosis, such as those with ECOG performance status of at least two and those with stable brain metastases, also derived clinical benefit with the approved 40 milligram starting dose of afatinib used in clinical trials. The main limitations of this analysis are the retrospective nature of the GioTag study and the potential for selection bias.
SPEAKER 1: However, to minimize this, the study only included consecutive patients who fulfilled all of the inclusion criteria, and enrollment was limited to a maximum of 15 patients per site. The other main limitations of the study were the lack of a comparator arm, which limits interpretation of the results, and the small patient numbers in the subgroup analyses.
SPEAKER 1: In conclusion, together with findings for the overall study population, the results of the present analysis support sequential afatinib and osimertinib as a feasible therapeutic strategy, resulting in a median chemotherapy-free treatment time of 27.6 months for both the overall patient population who were treated in a real world setting and patients who received a 40 milligram starting dose of afatinib, a subgroup which more closely reflects the clinical trial setting.
SPEAKER 1: [MUSIC PLAYING]
