A Real-World Cohort Study of First-Line Afatinib in Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer in Vietnam

doi:10.21203/rs.3.rs-3399075/v1

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A Real-World Cohort Study of First-Line Afatinib in Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer in Vietnam

https://doi.org/10.21203/rs.3.rs-3399075/v1

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published 05 Feb, 2024

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Background: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam.

Methods: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability.

Results: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p>0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs 74.3%, p=0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8 – 18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patientsin the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs 13.8 months, p=0.045) and in those without versus with brain metastases at baseline (17.5 vs 15.1 months, p=0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and <40 mg (16.7 vs 16.9 months, p>0.05). The most common treatment-related adverse events (any grade/grade ≥3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%).

Conclusions: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

advanced non-small cell lung cancer

EGFR mutations

afatinib

first-line

Vietnam

Lung cancer remains a significant public health concern worldwide, with its burden increasing in many countries, including Vietnam. In 2019, Vietnam was ranked 37th in terms of the lung cancer mortality rate globally [1]. According to Globocan 2020 statistics, there are approximately 26,262 new cases of lung cancer in Vietnam each year, accounting for 14.4% of all cancer cases and ranking second after liver cancer (14.5%) among different cancer types [2]. Lung cancer-related deaths comprised approximately 19% of total deaths in Vietnam, with lung cancer being the second leading cause of cancer-related deaths, accounting for 19.4% [2].

The number of new lung cancer cases is projected to continue rising in Vietnam, particularly in the two major cities of Hanoi and Ho Chi Minh City, due to population growth, aging, and the impact of smoking and secondhand smoke exposure [3]. The overall 5-year survival rate for lung cancer in Vietnam is 14.8% [1].

The prevalence of epidermal growth factor receptor (EGFR) mutations in Asian populations, including Vietnam, ranges from 39.6–51.4%, while specifically in Vietnam, the reported rate of EGFR gene mutations in patients with adenocarcinoma of the lung ranges from 40.7–64.2%[4, 5]. A recent study conducted in over 350 Vietnamese patients with non-small cell lung cancer (NSCLC) from four hospitals revealed the presence of EGFR mutations in 35% of cases, KRAS mutations in 23%, ALK rearrangements in 7%, ROS1 rearrangements in 3%, BRAF mutations in 2%, and NRAS mutations in 0.6% [6].

The current guidelines for the diagnosis and treatment of lung cancer in Vietnam recommend the use of first-generation (erlotinib, gefitinib), second-generation (afatinib), or third-generation (osimertinib) tyrosine kinase inhibitors (TKIs) as first-line treatment for advanced or metastatic NSCLC patients [7]. Afatinib, a second-generation TKI, has been approved for the treatment of EGFR-mutated NSCLC in Vietnam since 2018, with 50% coverage by health insurance [1, 7].

However, real-world data on the effectiveness and tolerability of afatinib in Vietnam are limited, as they have mostly been derived from single-center studies with small sample sizes [8].

Therefore, it is important to obtain representative real-world evidence on the effectiveness and tolerability of afatinib in NSCLC patients from different hospitals and cancer centers across Vietnam. This study aims to evaluate the response rate, time-to-treatment failure, and safety profile of first-line afatinib in EGFR-mutated NSCLC in a real-world multicenter setting in Vietnam.

Study design

This multicenter retrospective observational study was conducted in nine hospitals across Vietnam. The nine hospitals are Bach Mai Hospital, Vietnam National Cancer Hospital, Ho Chi Minh City Oncology Hospital, Cho Ray Hospital, Thong Nhat Hospital, National Lung Hospital, 108 Military Central Hospital, Hanoi Medical University Hospital, and Hanoi Oncology Hospital.

EGFR mutation NSCLC patients who received afatinib as first-line treatment between April 2018 and June 2022 were enrolled, and patient medical records were reviewed. The study and protocol were approved by each Institutional Review Board. Key clinical outcomes included overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. Key subgroup analyses included EGFR mutation categories, brain metastases at baseline, and starting dose/dose adjustment of afatinib.

Study population

Patients were required to have histologically confirmed advanced NSCLC (inoperable IIIB-IIIC stage, recurrences, stage IV), first-line treatment, and EGFR mutations (including common mutations (Exon 19 deletion, L858R mutation) and other uncommon EGFR mutations). Patients with severe hepatic or renal impairment or serious comorbidities, other malignant tumors, and the de novo T790M mutation were excluded.

Procedures

The initial afatinib dose, ranging from 20 mg to 40 mg, was selected by physicians' decisions and determined based on patient characteristics, including age, Eastern Cooperative Oncology Group performance status (PS), and body surface area. Afatinib was given until symptomatic disease progression or the occurrence of intolerable side effects. In cases of limited progression, the decision to pursue definitive local therapy and to continue treatment with afatinib is made by a multidisciplinary team in the respective centers. The Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria were used to evaluate the best tumor response. The best clinical tumor response was recorded as complete response, partial response, stable disease, or progressive disease. The TTF is defined as the time from the first dose of afatinib to the date of treatment discontinuation due to progression, intolerance, or death. Patients who stopped treatment or switched to another EGFR TKI for other reasons were considered censored observations. Side effects documented in medical records were collected and graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) [9].

Statistical analysis

Data were analyzed using IBM SPSS Statistics for Windows version 26.0 (IBM Corp., Armonk, NY). The presentation of continuous data as the mean ± standard deviation or median (interquartile range) and categorical data as the number (percentage) was dependent on their distribution. Differences between categorical variables were tested using the chi-square test or Fisher’s exact test. For continuous variables, the differences were compared using independent t tests or Mann‒Whitney U tests. Multivariable logistic binary regression with a forward selection approach was employed for the analysis of factors related to ORR. The TTF was estimated by the Kaplan–Meier method and compared by the log-rank test. A stepwise forward selection strategy was used to identify parameters for multivariate Cox proportional hazard regression models to evaluate factors associated with TTF. A p value of < 0.05 was considered statistically significant.

Patient characteristics

Out of the 343 patients treated with first-line afatinib included in the analysis, the majority (n = 336) had adenocarcinoma, while squamous cell carcinoma was observed in 6 cases and adenosquamous cell carcinoma in one case. The patient characteristics are described in detail in Table 1. The average age of the patients in the study was 63.2 ± 9.7 years. Overall, 56.6% of patients were male, 93.1% had good performance status (PS 0–1), 72.6% were nonsmokers or former smokers, and 91.0% were in stage IV. Most patients had adenocarcinoma histology (98.0%), while a small percentage had squamous cell carcinoma (1.7%) or adenosquamous carcinoma (0.3%). The number of patients with brain metastases and liver metastases was 87 (25.4%) and 33 (9.6%), respectively. Common mutations, including exon 19 deletion (Del19) and L858R mutation (L858R), were observed in 251 patients (73.2%), with Del19 mutation in 161 patients (46.9%) and L858R mutation in 90 patients (26.2%). The patients who received < 40 mg daily as the initial dose tended to be older than those who received 40 mg daily (64.0 ± 9.6 vs. 61.9 ± 9.8 years); however, this difference was not statistically significant (p = 0.056). There were no significant differences in sex, smoking history, performance status, stage, brain metastasis, liver metastasis, or EGFR mutations (Del19/L858R/uncommon mutations) between the two groups of starting doses.

Table 1. Demographic and clinical characteristics of patients

As shown in Table 2, most of the patients started with afatinib 30 mg once daily (58.6%), followed by 40 mg once daily (39.9%) and 20 mg once daily (1.5%). After one month of treatment, most of them could be maintained with the starting dose (81.9%). The number of patients requiring dose increases and dose reductions after one month was 25 (7.3%) and 37 (10.8%), respectively. Dose reductions due to tolerance were needed by 23.6% during the treatment. The optimal afatinib dosage, determined as the dose that could effectively manage the patient's disease while maintaining tolerable side effects, was most prescribed at 30 mg once daily (62.1%), followed by 40 mg once daily (33.2%) and 20 mg once daily (4.7%). Among the patients with baseline brain metastases, 27.6% had concurrent whole brain radiation, and 16.1% had gamma knife radiosurgery.

Table 2

Afatinib dosage and treatment features

Objective response

The overall objective response rate (ORR) was 78.1% in all patients, with 12.2% achieving a complete response and 65.9% achieving a partial response (Table 3).

Among the common mutation group, the ORR for the Del 19 group was higher than that for the L858R group, although the difference did not reach statistical significance (82.6% vs. 73.3%, p = 0.082). The ORR for the uncommon mutation group (including compound mutations) was 75.0%, which tended to be lower than that of the common mutation group; however, this difference was not statistically significant (p = 0.419).

The ORR for the 87 patients with brain metastases was 71.3%, with 24 patients receiving whole-brain radiation therapy and 14 patients undergoing gamma knife radiosurgery (Table 2). This response rate was lower than that of the group without brain metastases (80.5%), but the difference was not statistically significant (p = 0.073).

Univariate analysis was performed for factors influencing the objective response rate, such as age (≥ 65 years, < 65 years old), sex, performance status (PS), smoking status, mutation type, disease stage, and brain metastases. However, no statistically significant differences were found in these factors (Table 3).

We utilized multivariable logistic binary regression with a forward selection approach to examine factors associated with ORR. Two factors were identified as related to ORR: performance status (PS 0–1 vs. PS 2–3) and starting dose (40 mg vs. <40 mg). (Table 3)

Table 3. Overall Response Rate and Related Factors

Time to treatment failure

The median follow-up time was 26.2 months (95% CI 24.1 to 28.3 months) from the start of afatinib treatment. At the time of analysis in January 2023, 205 (59.8%) patients had an event of time to treatment failure (TTF). Among the censored patients, 103 patients were still receiving afatinib, while 34 patients had to switch to another TKI due to financial problems or drug supply issues. The median TTF (mTTF) was 16.7 months in all patients (Fig. 1a).

Figure 1. Kaplan–Meier curve of the TTF of the study population (A), the TTF stratified by EGFR mutations (B) and the TTF stratified by brain metastasis at baseline. Abbreviations: TTF: time-to-failure treatment, EGFR: Epidermal Growth Factor Receptor

The mTTF was 17.5 months in the common mutation group and 13.8 months in the uncommon mutation group (p = 0.045) (Fig. 1b). In the group of patients with brain metastases, the mTTF was 15.1 months, which was significantly lower than that (17.5 months) in patients without brain metastases at baseline (p = 0.049) (Fig. 1c).

When analyzing the factors influencing TTF using Cox regression multivariate analysis, we observed that the mutation type (common or uncommon) and the presence or absence of brain metastases were independent prognostic factors affecting TTF (Table 4).

Table 4. Time to Treatment Failure and Related Factors

Dose Adjustment

The response rates in patients receiving an initial dose of 40 mg and < 40 mg were 83.9% and 74.3%, respectively, with a statistically significant difference (p = 0.034) (Table 3). On univariate analysis, the only factor found to have an influence on ORR was the starting dose, and it remained a prognostic factor in the multivariate analysis. However, there was no significant difference in mTTF between the two initial doses (16.7 months vs. 16.9 months, p = 0.755) (Fig. 2a).

Figure 2. Kaplan–Meier curve of TTF among patients stratified by dosage factors: starting dose (A), dose reduction (B), dose adjustment after one month (C) and optimal dose (D). Abbreviations: TTF: time-to-failure treatment.

The mTTF was significantly longer in patients with dose reduction than in those without dose reduction (22.0 months vs 15.7 months, p < 0.001) (Fig. 2b). However, there was no significant difference in mTTF between the patients who needed dose adjustment, either through escalation or reduction, after one month of treatment and those who maintained their initial dose after one month (19.4 months vs 16.1 months, p = 0.192) (Fig. 2c). Analyzing patients maintaining different optimal doses revealed that those with a tolerable dose of < 40 mg had a significantly longer mTTF than those with a tolerable dose of 40 mg (18.5 months vs. 15.2 months, p = 0.003) (Fig. 2d). Multivariate analysis indicated that dose reduction status and tolerable dose maintained during the treatment could result in different mTTFs (Table 4).

Side effects

The most commonly observed adverse events included diarrhea (55.4%), rash (51.9%), paronychia (35.3%), stomatitis (22.2%), and dry skin (14.9%). Most of them were grades 1 and 2, and grade 3 was reported only with diarrhea (3.5%), rash (3.2%), paronychia (5.0%), and stomatitis (1.2%) (Table 5). No patients had grade 4 adverse events. The incidence of liver enzyme elevation was also low (9.9%), and no patients experienced interstitial lung disease. Diarrhea (any grade and grade 3) was more common in the group with a starting dose of 40 mg than in the group with a starting dose < 40 mg (p = 0.027 and p = 0.016, respectively). Stomatitis of any grade was more prevalent in the group with a starting dose of 40 mg (p = 0.047); however, there was no significant difference between the two groups in terms of grade 3 stomatitis.

Table 5. Most common treatment-related adverse events

The median TTF (mTTF) for all patients was 16.7 months, and the median follow-up time was 26.2 months (Fig. 1a). Compared to real-world data worldwide of mTTF ranging from 13.1–18.7 months [10–15], the Vietnamese population showed similar effectiveness of first-line afatinib. In the common mutation group, the mTTF extended to 17.5 months, while in the uncommon mutation group, it was notably shorter at 13.8 months (p = 0.045). (Fig. 1b). These results once again demonstrate the consistent effectiveness of afatinib in both the common and uncommon mutation groups. Among patients with brain metastases, the mTTF was 15.1 months, which was significantly shorter than the 17.5 months observed in those without brain metastases at baseline (p = 0.049) (Fig. 1c). However, the mTTF in patients with brain metastases at baseline is consistent with those in studies from Korea (14.8 months) [10] and China (15.6 months) [16]. These findings support the clinical activity of afatinib in EGFR mutation-positive patients with NSCLC and asymptomatic brain metastases. In multivariate analysis using Cox regression, we observed that the mutation type (common or uncommon) and the presence or absence of brain metastases remained independent prognostic factors affecting TTF (Table 4).

In a previous study in Vietnam, we observed that most patients were prescribed a starting dose of 30 mg of afatinib [8]. In this retrospective study, a significant proportion of patients began treatment with afatinib at 30 mg once daily (58.6%), followed by 40 mg once daily (39.9%) and 20 mg once daily (1.5%). This is different from other real-world studies in first-line afatinib in the region. The response rates in patients receiving an initial dose of 40 mg and < 40 mg were 83.9% and 74.3%, respectively, showing a statistically significant difference (p = 0.034) (Table 3). In multivariate analysis regarding factors related to ORR, the starting dose remained a prognostic factor. Studies with Taiwanese patients with EGFR Del 19 or L858R mutations showed no difference in the overall response rate between the 30 mg and 40 mg starting doses [17, 18]. The difference observed in our study may be attributed to the fact that more than 1/4 of the study population had uncommon mutations (26.8%). However, the difference between the initial doses did not affect the mTTF (16.7 months vs 16.9 months, p = 0.755) (Fig. 2a). This is consistent with the findings of other real-world studies [17, 19–22].

In this study, the mTTF was longer in patients with dose reduction than in those without dose reduction (22.0 months vs. 15.7 months, p < 0.001) and in those with an optimal dose of < 40 mg than in those with an optimal dose of 40 mg (18.5 months vs. 15.2 months, p = 0.003). Multivariate analysis indicated that dose reduction and an optimal dose of < 40 mg during the treatment could be favorable factors for mTTF (Table 4). Our data with an mTTF of 22.0 months in patients with dose reduction and 19.4 months in patients with dose adjustment are consistent with the finding that dose reduction or adjustment of afatinib can reduce the frequency and severity of treatment-related adverse events (TRAEs) without compromising treatment effectiveness [17, 21, 23].

Regarding adverse effects, we did not encounter any additional adverse effects other than those already documented and reported for afatinib (Table 5). Diarrhea (any grade and grade 3) was more common in the group with a starting dose of 40 mg than in the group with a starting dose < 40 mg (p = 0.027 and p = 0.016, respectively), while stomatitis of any grade was more prevalent in the group with a starting dose of 40 mg (p = 0.047); however, there was no significant difference between the two groups in terms of grade 3 stomatitis. The lower frequency observed in our study compared to previous prospective studies [24, 25] but comparable to real-world data in China [16] and South Korea [26] may be attributed to the nature of retrospective study designs.

The limitations of this study mainly relate to the retrospective study design, although patients were enrolled from nine hospitals. The study design might make the results less reliable than other standard prospective clinical trials with the potential variable quality and integrity of data, including length of follow-up. The multivariate analysis with a forward selection approach can be susceptible to selection bias, as it tends to favor variables that have a significant effect early in the selection process. In addition, the starting dose of afatinib varied based on the treating physician's decision, potentially introducing selection bias that is challenging to interpret. Nevertheless, our study represents real-world clinical practice and provides useful insights regarding the use of first-line afatinib for the treatment of advanced EGFR mutation-positive NSCLC in Vietnam. Another noteworthy point is that the mTTF is comparable, despite our patients having more than one-fourth uncommon mutations and 60% starting the dose with < 40 mg of afatinib. Our direction for future research is to conduct a prospective study to assess the efficacy of an initial 30 mg dose of afatinib in treating Vietnamese patients.

This first multicenter real-world data from Vietnam demonstrate consistent effectiveness and tolerability of first-line afatinib in Vietnamese patients, aligning with randomized controlled trials (RCTs) and real-world evidence (RWE).

The response rate was 78.1% in all patients, 79.3% in patients with common mutations and 75% in patients with uncommon mutations. The median time to treatment failure (mTTF) was 16.7 months in all patients, 17.5 months in patients with common mutations and 13.8 months in patients with uncommon mutations. In patients with brain metastases, the objective response rate (ORR) was 71.3%, and the mTTF was 15.1 months. There was no significant difference in mTTF between patients initiating treatment with a dose below 40 mg and those initiating treatment with a dose of 40 mg.

The most common adverse events (TRAEs; any grade/grade ≥ 3) reported were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). During the treatment process, 81 patients (23.6%) needed dose reduction due to tolerability issues, but dose reduction did not compromise treatment efficacy.

These findings are consistent with other real-world studies and support the conclusion of the RealGiDo study, which reported an mTTF of 18.7 months [14].

In summary, the multicenter real-world data from Vietnam confirm the effectiveness and tolerability of first-line afatinib in Vietnamese patients, consistent with RCTs and RWE. The study provides valuable insights into response rates, mTTF, and safety profiles, highlighting the importance of individualized dosing and proactive management of adverse events to optimize treatment outcomes. Further research and studies are warranted to enhance our understanding of afatinib in the Vietnamese population and improve patient care.

Confidence interval

CTCAE v5.0

Common Terminology Criteria for Adverse Events version 5

ECOG

Eastern Cooperative Oncology Group

EGFR

Epidermal growth factor receptor

Hazard ratio

mTTF

Median time-to-treatment failure

NSCLC

Non-small cell lung cancer

Odds ratio

ORR

Objective response rate

Performance status

RCT

Randomized controlled trial

RWE

Real-World Evidence

Standard deviation

TKI

Tyrosine kinase inhibitor

Ethics approval and consent to participate

The Human Research Ethics Committee of the Bach Mai Hospital in Hanoi, Vietnam approved this study (Approval Number: 916/BM-HĐĐĐ). The Human Research Ethics Committee of the Bach Mai Hospital has waived the informed consent for the study due to its retrospective nature and the absence of patient safety concerns. In addition, patient records were anonymized and de-identified before undergoing analysis.

Consent for publication

Not applicable.

Availability of data and materials

The de-linked and anonymized datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

ACKNOWLEDGEMENTS

We would like to extend our sincere appreciation to the Human Research Ethics Committee of Bach Mai Hospital in Hanoi, Vietnam, for their support and cooperation, including the waiver of informed consent. Their dedication to ethical standards greatly contributed to the success of this retrospective study.

Tran HTT, Nguyen S, Nguyen KK, Pham DX, Nguyen UH, Le AT, et al. Lung Cancer in Vietnam. J Thorac Oncol. 2021;16(9):1443–8.
International Agency for Research on Cancer (IARC). Viet Nam [Internet]. 2020 [cited 2023 Jan 10]. Available from: https://gco.iarc.fr/today/data/factsheets/populations/704-viet-nam-fact-sheets.pdf.
Nguyen SM, Deppen S, Nguyen GH, Pham DX, Bui TD, Tran TV. Projecting Cancer Incidence for 2025 in the 2 Largest Populated Cities in Vietnam. Cancer control: journal of the Moffitt Cancer Center. 2019;26(1):1073274819865274.
Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac oncology: official publication Int Association Study Lung Cancer. 2014;9(2):154–62.
Mai KT, Pham CP, Nguyen LT, Vo QTT, Anh NT, Binh NHUY, et al. Prevalence and clinicopathological factors of the EGFR mutation status of Vietnamese non-small cell lung cancer patients. J Clin Oncol. 2019;37(15suppl):e13120–e.
Dang A-TH, Tran V-U, Tran T-T, Thi Pham H-A, Le D-T, Nguyen L, et al. Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population. Sci Rep. 2020;10(1):2707.
Ministry of Health of Vietnam. Decision No. 4825/QD-BYT Guidelines for diagnosis and treatment of non-small cell lung cancer 2018.
Vu TH, Nguyen HTT, Dao LK, Duong CK, Nguyen CV, Doan TT, et al. Effectiveness and Tolerability of First-Line Afatinib for Advanced EGFR-Mutant Non-Small Cell Lung Cancer in Vietnam. Asian Pac J Cancer Prev. 2021;22(5):1581–90.
Common terminology criteria for adverse events v5.0 (CTCAE). Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 5.0, DCTD, NCI, NIH, DHHS, Publish Date: Nov 27, 2017.
Jung HA, Hong MH, Lee HW, Lee KH, Kim IH, Min YJ, et al. Totality outcome of afatinib sequential treatment in patients with EGFR mutation-positive non-small cell lung cancer in South Korea (TOAST): Korean Cancer Study Group (KCSG) LU-19-22. Translational lung cancer research. 2022;11(7):1369–79.
Su VY, Yang KY, Huang TY, Hsu CC, Chen YM, Yen JC, et al. The efficacy of first-line tyrosine kinase inhibitors combined with co-medications in Asian patients with EGFR mutation non-small cell lung cancer. Sci Rep. 2020;10(1):14965.
Kim T, Jang TW, Choi CM, Kim MH, Lee SY, Chang YS et al. Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR Positive Advanced Non-Small Cell Lung Cancer: Updated Analysis of the RESET Study. Cancer Res Treat. 2023.
Ito K, Morise M, Wakuda K, Hataji O, Shimokawaji T, Takahashi K, et al. A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903. ESMO open. 2021;6(3):100115.
Halmos B, Tan EH, Soo RA, Cadranel J, Lee MK, Foucher P et al. Impact of afatinib dose modification on safety and effectiveness in patients with EGFR mutation-positive advanced NSCLC: Results from a global real-world study (RealGiDo). Lung cancer (Amsterdam, Netherlands). 2019;127:103 – 11.
Fujiwara A, Yoshida M, Fujimoto H, Nakahara H, Ito K, Nishihama K, et al. A Retrospective Comparison of the Clinical Efficacy of Gefitinib, Erlotinib, and Afatinib in Japanese Patients With Non-Small Cell Lung Cancer. Oncol Res. 2018;26(7):1031–6.
Wang S, Xing P, Yang K, Hao X, Ma D. Efficacy and safety of afatinib in a Chinese population with advanced lung adenocarcinoma with sensitive EGFR mutations. 2019;10(6):1461–8.
Yang CJ, Tsai MJ, Hung JY, Lee MH, Tsai YM, Tsai YC, et al. The clinical efficacy of Afatinib 30 mg daily as starting dose may not be inferior to Afatinib 40 mg daily in patients with stage IV lung Adenocarcinoma harboring exon 19 or exon 21 mutations. BMC Pharmacol Toxicol. 2017;18(1):82.
Chen YC, Tsai MJ, Lee MH, Kuo CY, Shen MC, Tsai YM et al. Lower starting dose of afatinib for the treatment of metastatic lung adenocarcinoma harboring exon 21 and exon 19 mutations. 2021;21(1):495.
Tu CY, Chen CM, Liao WC, Wu BR, Chen CY, Chen WC, et al. Comparison of the effects of the three major tyrosine kinase inhibitors as first-line therapy for non-small cell lung cancer harboring epidermal growth factor receptor mutations. Oncotarget. 2018;9(36):24237–47.
Lim CK, Wei YF, Tsai MS, Chen KY, Shih JY, Yu CJ. Treatment effectiveness and tolerability of afatinib at different doses in patients with EGFR-mutated lung adenocarcinoma: How low can we go? European journal of cancer (Oxford, England: 1990). 2018;103:32–40.
Liu CY, Wang CL, Li SH, Hsu PC, Chen CH, Lin TY, et al. The efficacy of 40 mg versus dose de-escalation to less than 40 mg of afatinib (Giotrif) as the first-line therapy for patients with primary lung adenocarcinoma harboring favorable epidermal growth factor mutations. Oncotarget. 2017;8(57):97602–12.
Liang SK, Hsieh MS, Lee MR, Keng LT, Ko JC, Shih JY. Real-world experience of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. Oncotarget. 2017;8(52):90430–43.
Lee SY, Choi CM, Chang YS, Lee KY, Kim SJ, Yang SH, et al. Real-world experience of afatinib as first-line therapy for advanced EGFR mutation-positive non-small cell lung cancer in Korea. Translational lung cancer research. 2021;10(12):4353–67.
Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin oncology: official J Am Soc Clin Oncol. 2013;31(27):3327–34.
Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomized controlled trial. Lancet Oncol. 2016;17(5):577–89.
Kim Y, Lee SH, Ahn JS, Ahn MJ, Park K, Sun JM. Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib. Cancer Res Treat. 2019;51(2):502–9.

[1] Table 1. Demographic and clinical characteristics of patients

[2] Table 2: Afatinib dosage and treatment features

[3] Table 3. Overall Response Rate and Related Factors

[4] Figure 1. Kaplan–Meier curve of the TTF of the study population (A), the TTF stratified by EGFR mutations (B) and the TTF stratified by brain metastasis at baseline. Abbreviations: TTF: time-to-failure treatment, EGFR: Epidermal Growth Factor Receptor

[5] Table 4. Time to Treatment Failure and Related Factors

[6] Figure 2. Kaplan–Meier curve of TTF among patients stratified by dosage factors: starting dose (A), dose reduction (B), dose adjustment after one month (C) and optimal dose (D). Abbreviations: TTF: time-to-failure treatment.

[7] Table 5. Most common treatment-related adverse events

Tables 1 to 5 are available in the Supplementary Files section

No competing interests reported.

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A Real-World Cohort Study of First-Line Afatinib in Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer in Vietnam

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Time to treatment failure

Dose Adjustment

Side effects

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CONCLUSIONS

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Supplementary Files

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Journal Publication

Version 1