At the 2022 ESMO Annual Meeting, a multi-center retrospective study from the Netherlands analyzed real-life data of osimertinib in patients with metastatic EGFR-mutated NSCLC of different ages, body mass indexes and trough plasma concentrations.

Lung cancer is the malignant tumor with the highest mortality rate in the world, and non-small cell lung cancer (NSCLC) accounts for 80%~85% of all lung cancer types^[1]. Epidermal growth factor receptor (EGFR) is the most common driver mutation gene in NSCLC. Guidelines such as NCCN and CSCO recommend the first, second and third generation EGFR-TKIs including gefitinib, erlotinib, icotinib, afatinib, dacomitinib, osimertinib and ametinib as Class 1A evidence for EGFR mutation-positive advanced NSCLC. first-line treatment, and NCCN guidelines recommend osimertinib as the first choice.^[2]. Osimertinib has been widely used clinically. How effective is it in the real world? At the 2022 ESMO Annual Meeting, a multi-center retrospective study from the Netherlands analyzed real-life data of osimertinib in patients with metastatic EGFR-mutated NSCLC of different ages, body mass indexes and trough plasma concentrations. The Yimaitong editor is organized as follows.

1 Research Background

Osimertinib is currently the first-line standard treatment for patients with metastatic NSCLC with EGFR-sensitive mutations, and is also the standard second-line treatment for T790M-positive patients who have progressed on first- and second-generation EGFR-TKIs. Because there are limited data relating the efficacy of osimertinib to body mass index (BMI), age, and trough plasma concentrations, further studies are warranted^[2].

2 Research design

This is a multi-center retrospective study from the Netherlands. The inclusion criteria for the study are: ① Age ≥ 18 years old; ② Advanced or metastatic EGFR-positive NSCLC; ③ Adherence to osimertinib treatment from January 2, 2016 to January 3, 2022; ④ Response to treatment. The primary endpoint of the study is progression-free survival (PFS), and the secondary endpoints are overall survival (OS), objective response rate (ORR), and disease control rate (DCR). The researchers continued to collect data for 3 months before disease progression among enrolled patients, and used the Kaplan-Meier method and multivariable Cox proportional hazards models to compare age, BMI, and steady-state drug trough concentration (Cmin, SS)^[2] in different subgroups.

3 Research results

The study ultimately screened 294 patients, with a median follow-up time of 14.3 months. The average age of the enrolled patients was 67 years old (29-87 years old), the average BMI was 25.3 (17.6-67.1), about 66% were female, about 90% were white, 19del accounted for about 54%, L858R accounted for about 30%, and other mutations accounted for 17% (Table 1) ^[2].

table 1 Baseline characteristics of enrolled patients

In this study, 118 (40%) patients with advanced or metastatic EGFR-positive NSCLC were treated with osimertinib in the first-line treatment, 134 (46%) patients were treated with osimertinib in the second-line treatment, and 42 (14%) patients were treated with osimertinib in the third-line and later-line treatments. The corresponding median PFS were 14.6 months (95%). CI, 10.2–20.0 months), 13.7 months (95% CI, 11.1–15.6 months), and 8.7 months (95% CI, 5.1–12.7 months). Among patients who received first-line, second-line, third-line and later-line treatment, the ORR and DCR results were similar, 68% and 96% (1L), 62% and 93% (2L), and 69% and 91% (3L+), respectively. In addition, PFS and OS were similar between patients over 70 years old and those under 70 years old (PFS: aHR=0.93; 0.68–1.28; OS: aHR=1.14; 0.77–1.68) (Figure 1).

Figure 1 PFS of patients in different age groups

However, in patients with low BMI (20.0 kg/m²), PFS and OS were significantly lower (Figure 2, Figure 3), but due to the small number of cases in this group (n=8), there was no statistical significance.

Figure 2 PFS of patients with different BMIs

Figure 3 OS

of patients with different BMIs In addition, the study found that high blood drug trough concentration state is associated with low PFS (aHR=1.92, 95% CI=1.10–3.37) (Figure 4) ^[2].

Figure 4 PFS of patients stratified by different plasma trough concentrations

Expert profile

Yao Wei Professor

• Chief physician

• Director of the Department of Respiratory Medicine, the Third Affiliated Hospital of Chongqing Medical University

• Former deputy director of the Department of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University

• Postdoctoral fellow in the Department of Respiratory Medicine, Peking Union Medical College Hospital , Harvard Medical School, USA Visiting scholar at Dana-Farber Cancer Institute

• ’s main research interests include interstitial lung disease, pathogenesis of chronic obstructive pulmonary disease , etc. He has been engaged in clinical, teaching, and scientific research work for more than 20 years. Hosted and participated in 4 National Natural Science Foundation projects, participated as a researcher in many Ministry of Health and Ministry of Science and Technology projects, and published more than 20 papers in foreign journals included in SCI and national statistical source journals.

Academic appointment currently

• Deputy Chairman of the Respiratory Branch of Chongqing Medical Association

• Member of the Endoscopy Branch of the Chinese Medical Doctor Association

• Deputy leader of the Interstitial Disease Group of Respiratory Branch of Chongqing Medical Association

• Deputy leader of the Interstitial Disease Group of Respiratory Branch of Chongqing Medical Association

• Deputy leader of the early cancer diagnosis and treatment group of Respiratory Branch of Chongqing Medical Association

Academic appointment Former member of the 7th Annual Committee of the Respiratory Branch of the Chinese Medical Association

Member of the 9th Interventional Respiratory Medicine Group

Expert comments

Compared with the results of the FLAURA study, the PFS and OS of patients who received first-line treatment with osimertinib in this study were lower, while the OS of patients who received second-line treatment was slightly longer. In addition, the study found that the age of the patient was not related to PFS, while low BMI (20.0 kg/m

²

) and high plasma trough concentration may be related to poorer treatment outcomes of osimertinib. In the future, it is recommended to expand the sample size and conduct in-depth research on the exact relationship between BMI and high plasma trough concentration and osimertinib, so as to strive to bring greater survival benefits to more patients.

Approval number: CN-106492, Validity period: 2023-3-6

Statement: This material is supported by AstraZeneca and is for reference only by medical and health professionals.

References

[1] Qian Jiannan, Yang Shaoyu, Chen Xueqin, Ma Shenglin. Updated interpretation of the 2022 third edition of "NCCN Non-small Cell Lung Cancer Clinical Practice Guidelines" [J]. Journal of Practical Oncology, 2022, 37(03):197-204.

[2] Veelen A V, Veerman M G D, Verschueren M, et al. 1130P Real-world data of osimertinib (osi) for the treatment of metastatic epidermal growth factor receptor (EGFR+) non-small cell lung cancer (NSCLC) patients (pts), with a focus on age, body mass index (BMI) and trough levels[J]. Annals of Oncology, 2022, 33: S1067-S1068.

Reviewer: Faline

Typesetting: Yuna

Execution: Yuna

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