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. 2022 Sep;9(3):333-345.
doi: 10.1007/s40801-022-00302-w. Epub 2022 Jun 3.

Retrospective Analysis of Real-World Management of EGFR-Mutated Advanced NSCLC, After First-Line EGFR-TKI Treatment: US Treatment Patterns, Attrition, and Survival Data

Jorge Nieva  1 , Karen L Reckamp  2 , Danielle Potter  3   4 , Aliki Taylor  3 , Ping Sun  5
Affiliations

Retrospective Analysis of Real-World Management of EGFR-Mutated Advanced NSCLC, After First-Line EGFR-TKI Treatment: US Treatment Patterns, Attrition, and Survival Data

Jorge Nieva et al. Drugs Real World Outcomes. 2022 Sep.

Abstract

Background and objectives: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard-of-care first-line (1L) treatment for EGFR mutation-positive advanced/metastatic non-small cell lung cancer. In 2015, osimertinib, a third-generation EGFR-TKI, received US accelerated approval for second-line (2L) EGFR T790M-positive non-small cell lung cancer treatment. The objective of this US study was to characterize treatment patterns, attrition, and survival in EGFR mutation-positive non-small cell lung cancer, after 1L first-/second-generation EGFR-TKI treatment.

Methods: We retrospectively analyzed 1029 patients diagnosed with stage IIIB/IV non-small cell lung cancer from 1 January, 2011 to 31 December, 2018 using the US electronic medical record CancerLinQ Discovery® database. Demographic/disease characteristics, EGFR mutations, treatments, and death dates were collected.

Results: From 1 January, 2011 to 31 December, 2014 (< 2015 cohort), 519 patients received 1L EGFR-TKIs and 510 between 1 January, 2015 and 31 December, 2018 (≥ 2015 cohort). Median follow-up from advanced diagnosis was 19.8 months (interquartile range: 9.9-33.4 months). Twenty-eight percent of patients (288/1029) died without receiving 2L, and 52% (539/1029) initiated 2L with 35% (186/539) receiving osimertinib; in the < 2015 and ≥ 2015 cohorts, the same proportion initiated 2L (52%; 272/519 vs 267/510, respectively). Median overall survival from advanced diagnosis for patients initially diagnosed with stage I-IIIA disease was 43.3 months (95% confidence interval 30.9-73.7), vs 26.4 months (95% confidence interval 24.4-28.1) for stage IIIB-IV; all-cause mortality hazard ratio: 1.56 (95% confidence interval 1.2-2.0; p = 0.001).

Conclusions: We identified disease stage, performance status, and central nervous system metastasis as survival predictors, highlighting the importance of optimal 1L treatment selection. Over a quarter of patients died before initiating 2L; half progressed after 1L and received 2L, of whom a third received 2L osimertinib.

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Conflict of interest statement

J. Nieva reports ownership of stock/shares for Cansera, Epic Sciences, and Quantgene and has received honoraria from AstraZeneca, Fujirebio, Genentech, Western Oncolytics, Takeda, and Amgen. J. Nieva has received research grants/funds from Genentech and Merck & Co. K. Reckamp received personal fees for consulting from Amgen, AstraZeneca, Blueprint, Boehringer Ingelheim, Calithera, Euclises, Genentech, Guardant, Janssen, Lilly, Merck KGA, Precision Health, Seattle Genetics, Takeda, and Tesaro. K. Reckamp received (institution) research grants/funds from AbbVie, Acea, Adaptimmune, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, GlaxoSmithKline, Guardant, Janssen, Loxo Oncology, Molecular Partners, Seattle Genetics, Spectrum, Takeda, Xcovery, and Zeno. D. Potter was an employee of AstraZeneca when this research was conducted. D. Potter joined ASCO and CancerLinQ after participating in this study. This study and related conclusions reflect the independent work of study authors and do not necessarily represent the views of ASCO or CancerLinQ. A. Taylor and P. Sun are employees of AstraZeneca and report ownership of stocks/shares. Medical writing support for the development of this article, under the direction of the authors, was provided by Preeyah Purang, BSc and Gemma White, MSc, of Ashfield MedComms UK, an Ashfield Health company, and was funded by AstraZeneca.

Figures

Fig. 1
Fig. 1
Summary of patient selection. 1L first-line, CLQD CancerLinQ Discovery®, EGFR epidermal growth factor receptor, EGFRm epidermal growth factor mutation-positive, EGFR-TKI epidermal growth factor receptor-tyrosine kinase inhibitor, NSCLC non-small cell lung cancer, SCLC small cell lung cancer
Fig. 2
Fig. 2
Patient disposition by first-line (1L) progression. aCalculated as the proportion of patients who progressed on 1L epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment. bReceipt of osimertinib as a second-line (2L) or later treatment; calculated as the proportion of patients who tested positive for T790M. cReceipt of osimertinib as a 2L or later treatment; calculated as the proportion of patients who tested negative for T790M
Fig. 3
Fig. 3
Overall survival from the index date to the last follow-up. CNS central nervous system, ECOG European Cooperative Oncology Group, EGFR epidermal growth factor receptor, Ex19del exon 19 deletion, OS overall survival
Fig. 4
Fig. 4
Kaplan–Meier estimates of overall survival from the index date to the last follow-up (months) by A European Cooperative Oncology Group performance status at index, B stage at diagnosis, C epidermal growth factor receptor (EGFR) mutation detail, and D cohort (< 2015 and ≥ 2015)
Fig. 4
Fig. 4
Kaplan–Meier estimates of overall survival from the index date to the last follow-up (months) by A European Cooperative Oncology Group performance status at index, B stage at diagnosis, C epidermal growth factor receptor (EGFR) mutation detail, and D cohort (< 2015 and ≥ 2015)
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