Name:
Afatinib in NSCLC with uncommon EGFR mutations
Description:
Afatinib in NSCLC with uncommon EGFR mutations
Thumbnail URL:
https://cadmoremediastorage.blob.core.windows.net/a64b9e6a-3826-43f6-a53b-23613be9e84f/videoscrubberimages/Scrubber_10.jpg
Duration:
T00H08M46S
Embed URL:
https://stream.cadmore.media/player/a64b9e6a-3826-43f6-a53b-23613be9e84f
Content URL:
https://cadmoreoriginalmedia.blob.core.windows.net/a64b9e6a-3826-43f6-a53b-23613be9e84f/YANG FINAL APRIL 2021.mp4?sv=2019-02-02&sr=c&sig=qGnkiwSRDiwOmNOmb4rie6j1YC%2FNQ4BEsv2W5tFH2%2BM%3D&st=2025-01-18T07%3A52%3A52Z&se=2025-01-18T09%3A57%3A52Z&sp=r
Upload Date:
2021-06-11T00:00:00.0000000
Transcript:
Language: EN.
Segment:1 Afatinib for the treatment of non-small cell lung cancer harboring uncommon EGFR mutations: a database of 693 cases .
[MUSIC PLAYING]
SPEAKER: On behalf of James Chin-Hsin Yang and his coauthors, in this video, we provide a summary of the paper "Afatinib for the Treatment of Non-Small Cell Lung Cancer, Harboring Uncommon EGFR Mutations, A Database of 693 Cases," which was recently published in the Journal of Thoracic Oncology. The objective was to provide a comprehensive analysis of clinical outcomes in patients with a non-small cell lung cancer harboring uncommon EGFR mutations, treated with a afatinib.
Segment:2 What was the purpose of the study?.
SPEAKER: [MUSIC PLAYING] EGFR-TKIs are now the standard of care for EGFR mutation-positive NSCLC, having demonstrated robust efficacy and tolerability benefits compared with standard treatments in clinical trials. However, most of these trials were limited to patients with tumors harboring the common EGFR mutations, Del-19 and L858R. Uncommon EGFR mutations identified in 7% to 23% of patients represent a heterogeneous group of around 600 variants and often coexist with other EGFR mutations within the same tumor, so-called compound mutations.
SPEAKER: Existing data suggests that uncommon mutations show a high degree of heterogeneity in terms of sensitivity to different EGFR-TKIs, supporting the use of a personalized treatment strategy for patients, depending on mutation type. Post-hoc analysis of the pivotal LUX-Lung trials showed that the second generation ErbB family blocker, afatinib, has clinical activity against the most prevalent uncommon mutations-- G719X, L861Q, and S768I-- and is approved in this setting.
SPEAKER: However, in general, prospective data on the efficacy of EGFR-TKIs against uncommon mutations are lacking. Nevertheless, several real-world studies have assessed the activity of EGFR-TKIs in patients with uncommon mutations. And these studies play an important complementary role to randomized trials for informing clinical decision-making.
SPEAKER: The aim of the current study was to analyze all the available data for afatinib in patients with NSCLC harboring uncommon EGFR mutations and to provide a searchable database of clinical outcomes.
Segment:3 How was the study undertaken?.
SPEAKER: [MUSIC PLAYING] This was a pooled analysis of data on patients with tumors harboring uncommon mutations who had been treated with afatinib. Data were collected prospectively from randomized clinical trials, compassionate use and expanded access programs, phase 3b trials, noninterventional studies, and case series or case studies.
SPEAKER: In addition, a systematic literature review was undertaken on September the 19th, 2019, and all identified cases with available outcome data were included. A total of 693 patients were included. 315 had not been previously treated with EGFR-TKI prior to afatinib, and 378 patients had received prior EGFR-TKI treatment. Patients were categorized into four key groups.
SPEAKER: Group one included those with tumors harboring T790M. Group two had exon 20 insertions but were T790M negative. Group three had major uncommon mutations, i.e., G719X, L861Q, and S768I, with or without any other mutation except T7ITM and exon 20 insertions. And group four had other uncommon mutations. Cases of compound mutations defined as at least two uncommon mutations with or without a common mutation were also analyzed.
SPEAKER: Central testing was performed only in patients enrolled in the LUX-Lung trials. In all other patients, mutation detection was undertaken locally, using different methodologies. Key endpoints were overall response rate, duration of response, and time to treatment failure, defined as the time from the start of therapy to treatment discontinuation for any reason or death. [MUSIC PLAYING]
Segment:4 What were the results?.
SPEAKER: 98 different uncommon mutations were identified.
SPEAKER: In TKI-naive patients, 40% had a major uncommon mutation, 24% had an exon 20 insertion, 12% had a de novo T790M mutation, 11% had other uncommon mutations, and 13% of patients had compound mutations. Of the compound mutations, nearly 2/3 harbored a major uncommon mutation. As expected, T790M was more prevalent in TKI pre-treated patients.
SPEAKER: Among the 315 TKI-naive patients, median TTF was longest in patients with compound mutations, at 14.7 months. In patients with a major uncommon mutation as part of a compound mutation, median TTF was 16.6 months. In patients with an isolated uncommon mutation, median TTF was 10.8 months. As expected, TTF was shorter in patients harboring exon 20 insertions, T790M, or other uncommon mutations.
SPEAKER: Strong activity with afatinib was observed in patients with compound mutations and those with major uncommon mutations, with objective response rates of 77% and 60% respectively. Durable responses were observed in several patients, with a median duration of response of over 17 months. Activity was also notable in patients harboring other uncommon mutations, with a response rate of 65%.
SPEAKER: Response rate was lower, at around 25%, in the T790M and exon 20 insertion groups. But some patients with exon 20 insertions demonstrated durable responses to afatinib. For TKI pre-treated patients, median TTF was again highest in patients with tumors harboring compound mutations at 5.8 months, especially those that included a major uncommon mutation, at 9.3 months.
SPEAKER: The objective response rate among TKI pre-treated patients was highest in those with other uncommon mutations at 36%, followed by compound mutations at 29%, and major uncommon mutations at 25%.
Segment:5 What is the significance of these findings?.
SPEAKER: To our knowledge, this study represents the most comprehensive analysis of clinical outcomes of EGFR-TKI treatment in patients with NSCLC harboring uncommon EGFR mutations.
SPEAKER: Our analysis showed that afatinib has strong clinical activity against major uncommon and compound EGFR mutations. In addition, in line with preclinical findings, afatinib showed broad activity against other uncommon EGFR mutations, including certain exon 20 insertions and very rare uncommon mutations. The widespread use and improvement in the sensitivity of next-generation sequencing assays are likely to improve the detection of EGFR mutations in the future, including detection of uncommon mutations.
SPEAKER: In this regard, our data will provide important information when considering optimal treatment for tumors with uncommon EGFR mutations, including compound mutations. A searchable database of outcomes by EGFR genotype has been created for individual genotype efficacy critique and accompanies the publication. This can be found at www.uncommonEGFRmutations.com. [MUSIC PLAYING]
Form Title Download
Form Title Bookmark
Form Title Share
Form Title Cite
