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Updated: Aug 5, 2026

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Treatment patterns and outcomes of second/third-line therapy in advanced non-small cell lung cancer with actionable
Hanxiao Chen1, Xiangjiao Meng2, Ling Cai3
1Department of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Abstract:
Treatment choices for metastatic non-small-cell lung cancer (NSCLC) after first-line targeted therapy progression are heterogeneous. This study aimed to characterize real-world treatment patterns and outcomes of advanced NSCLC harboring actionable genomic alterations (AGAs) in second- (2 L) or third-line (3 L) settings. This retrospective cohort study across six Chinese centers included stage IV NSCLC patients with confirmed AGAs. Therapies were divided into six categories: targeted monotherapy (T), targeted combinations (T+), chemotherapy monotherapy (C), chemotherapy combinations (C+), anti-angiogenic monotherapy (A), and other regimens (O). The primary outcome was the treatment pattern. Secondary outcomes included biomarker testing and effectiveness. A total of 658 patients were enrolled, with the majority harboring EGFR mutations (n = 590, 89.7%). In the 2 L-enrolled group (n = 602), T use declined from 75.3% in the 1 L setting to 49.3% in 2 L, while utilization of A + C increased to 16.5%. Within the EGFR-mutant subgroup, therapeutic sequences were highly dependent on 1 L TKI generation and T790M resistance status. Over half (51.1%) of T790M-negative patients continued T in 2 L following progression on 1 L first- or second-generation TKIs. Among the 3 L-enrolled patients (n = 56), A + C (35.7%) and C (14.3%) were predominant. The overall median real-world progression-free survival for the 2 L-enrolled group was 7.4 months in the 2 L setting (7.5 months for the EGFR-mutant subgroup) and 5.4 months in 3 L. This multicenter real‑world cohort predominantly comprised patients with EGFR‑mutant NSCLC, with smaller numbers of other AGA subtypes. Targeted therapies remain the cornerstone of later-line advanced NSCLC management. The prevalent real-world reliance on continued TKI therapy, even in T790M-negative patients, highlights the clinical dilemma of limited post-resistance options and the need to integrate emerging novel therapeutics.
Insights
Treatment patterns for advanced non-small-cell lung cancer (NSCLC) after initial targeted therapy show a shift towards chemotherapy combinations in later lines. Despite limited options, targeted therapies remain crucial, highlighting the need for novel treatments post-resistance.
Area of Science:
- Oncology
- Genomics
- Clinical Research
Background:
- Treatment selection for metastatic non-small-cell lung cancer (NSCLC) after first-line targeted therapy is inconsistent.
- Characterizing real-world treatment patterns and outcomes is essential for advanced NSCLC with actionable genomic alterations (AGAs).
Purpose of the Study:
- To analyze real-world treatment patterns and outcomes in second- (2L) and third-line (3L) settings for advanced NSCLC patients with AGAs.
- To evaluate the utilization of different therapy categories including targeted monotherapy (T), targeted combinations (T+), chemotherapy monotherapy (C), chemotherapy combinations (C+), and anti-angiogenic monotherapy (A).
Main Methods:
- Retrospective cohort study across six Chinese centers.
- Inclusion of stage IV NSCLC patients with confirmed AGAs.
- Categorization of therapies into T, T+, C, C+, A, and other regimens.
- Analysis of treatment patterns, biomarker testing, and effectiveness (progression-free survival).
Main Results:
- The cohort (n=658) was predominantly EGFR-mutant NSCLC (89.7%).
- In 2L (n=602), targeted therapy use decreased from 75.3% in 1L to 49.3%, with increased anti-angiogenic plus chemotherapy (A+C) use (16.5%).
- For T790M-negative patients progressing on first- or second-generation TKIs, over 51% continued targeted therapy in 2L.
- In 3L (n=56), A+C (35.7%) and C (14.3%) were predominant.
- Median real-world progression-free survival was 7.4 months in 2L and 5.4 months in 3L.
Conclusions:
- Targeted therapies remain central to later-line advanced NSCLC management, particularly for EGFR-mutant disease.
- The continued reliance on TKI therapy, even in T790M-negative patients, underscores limited post-resistance options.
- There is a critical need to integrate novel therapeutics to address treatment challenges in advanced NSCLC post-progression.
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