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Abstract

Background:

S-1, an oral chemotherapy combining tegafur, gimeracil, and oteracil, has shown efficacy comparable with docetaxel for advanced non-small cell lung cancer (NSCLC) in clinical trials. However, its real-world effectiveness and safety remain underexplored.

Methods:

This retrospective cohort study was conducted at 2 tertiary referral centers: National Cheng Kung University Hospital (NCKUH) from July 1, 2012 to July 1, 2023 (last follow-up in October 31, 2023) and Linkou Chang Gung Memorial Hospital (CGMH) from February 1, 2020 to January 31, 2023 (last follow-up in August 31, 2023). The study included 132 NSCLC patients receiving S-1 monotherapy (77 from CGMH and 55 from NCKUH). After excluding 31 patients with less than 2 weeks of treatment, 101 patients were analyzed.

Results:

The objective response rate (ORR) was 7.9%, and the disease control rate (DCR) was 44%. Median progression-free survival (PFS) and overall survival (OS) were 2.6 and 6.0 months, respectively. First-line or second-line S-1 therapy significantly improved DCR (61.1% vs 33.8%, P = .008) and PFS (4.2 vs 2.3 months, P < .001) compared with third-line or later use. Cox regression analysis confirmed earlier-line S-1 treatment (⩽ 2) as an independent predictor for PFS (hazard ratio: 2.01, 95% confidence interval: 1.15-3.51, P = .014). Severe adverse events (grade ⩾ 3) occurred in 7.9% of cases.

Conclusions:

S-1 monotherapy demonstrated comparable effectiveness and manageable toxicity in real-world settings, with significantly better outcomes when used as first-line or second-line treatment in NSCLC.

Keywords

Non-small cell lung cancer S-1 monotherapy real-world study efficacy and safety

Introduction

Lung cancer remains the leading cause of cancer-related deaths globally, accounting for approximately 1.8 million fatalities each year. Non-small cell lung cancer (NSCLC) represents around 85% of all lung cancer cases.¹ Despite notable advancements in therapeutic strategies, the 5-year survival rate for NSCLC continues to be alarmingly low, especially for patients with stages IVA-IVB, where it falls to less than 10%.² The identification of oncogenic driver mutations, such as EGFR mutations, has markedly improved treatment outcomes, providing a foundation for targeted therapeutic strategies and personalized cancer care.^3,4 However, approximately 30% of NSCLC patients do not possess detectable driver mutations in Asian (or Taiwan), which limits their eligibility for targeted therapeutic interventions.⁵ Current treatment guidelines for patients without identifiable driver oncogenes or those who have failed tyrosine kinase inhibitors (TKIs) propose several first-line therapeutic strategies. These include combination therapy with platinum-based chemotherapy and immune checkpoint inhibitors (ICIs); ICI monotherapy for patients with PD-L1 expression >50%, followed by platinum-based chemotherapy; or platinum-based chemotherapy followed by ICI.⁶ After failure to platinum-based chemotherapy, docetaxel remain the standard care of care for many years. However, the improvement of overall survival (OS) is modest (median OS 7 vs 4.6 months compared with best supportive care, P value: .047) and patient would experience relatively high incidence of grade 3/4 neutropenia and febrile neutropenia.^7,8 Therefore, there is a need for an alternative therapy that provided efficacy comparable with that of docetaxel, with a substantially improved side-effect profile.

S-1 is an oral chemotherapeutic agent composed of tegafur (a prodrug of 5-fluorouracil (5-FU), the primary cytotoxic component), gimeracil (a potent inhibitor of the 5-FU catabolic enzyme, which helps maintain 5-FU levels to enhance its cytotoxic effects), and oteracil potassium (which reduces gastrointestinal toxicity by inhibiting 5-FU activation in the gut) in a molar ratio of 1:0.4:1.⁹ Nokihara et al presented the results of the East Asia S-1 Trial in Lung Cancer (EAST-LC), a phase III randomized controlled study involving 1,154 Asian patients with advanced NSCLC who had previously received at least one platinum-based treatment. The study demonstrated that S-1 monotherapy is not inferior to docetaxel, with a hazard ratio of 0.95 (95% confidence interval (CI): 0.83-1.07), meeting the predefined non-inferiority margin of 1.2.¹⁰ Notably, patients in the S-1 monotherapy arm achieved higher scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), reflecting improved quality of life and greater tolerability of the chemotherapy.¹⁰ Based on these data, S-1 monotherapy is recommended as a second-line or later-line chemotherapy option for patients with advanced NSCLC and also suggested by Japanese guidelines.¹¹ S-1 has also been approved for use in NSCLC treatment in Taiwan.

Currently, there is a lack of real-world studies validating the efficacy and safety of S-1 monotherapy, as well as insufficient data on its use in earlier treatment lines compared with later stages. To address this gap, we conducted a multicenter study over 10 years involving advanced stage IV lung cancer patients treated with S-1 monotherapy.

Materials and methods

Patients

This retrospective study analyzed electronic medical records (EMRs) of patients with advanced NSCLC who received S-1 monotherapy at 2 tertiary academic referral centers in Taiwan. Eligible patients were treated at National Cheng Kung University Hospital (NCKUH) between July 1, 2012, and July 1, 2023, with follow-up completed in October 31, 2023, and at Linkou Chang Gung Memorial Hospital (CGMH) between February 1, 2020, and January 31, 2023, with follow-up completed in August 31, 2023. Eligible patients for this study were required to meet the following criteria: age greater than 18 years; histologically or cytologically confirmed locally advanced or metastatic NSCLC; received S-1 monotherapy; and had at least one measurable target lesion. Mutation testing was conducted with or without additional analyses, based on the clinician’s discretion. The EGFR genetic testing was performed for all patients, except those with squamous cell carcinoma, for whom the standard treatment consisted of chemotherapy with or without ICIs. Patients who received S-1 monotherapy for less than 2 weeks or who were treated in combination with other medications, such as other chemotherapeutic agents, TKIs, or immunotherapies, were excluded. For comprehensive staging, chest computed tomography (CT), with or without brain magnetic resonance imaging (MRI), and whole-body bone scans were conducted at the initiation of S-1 monotherapy, following the tumor-node-metastasis (TNM) classification system as defined in the 8th edition of the American Joint Committee on Cancer guidelines. Baseline patient characteristics recorded included age, sex, histological subtype, TNM stage, gene mutations, presence of metastases in the brain, liver, and adrenal glands, prior treatments with pemetrexed, TKIs, or immunotherapies, and the duration of S-1 monotherapy. All data were de-identified following approved protocols and the principles of the Declaration of Helsinki. The present study was reviewed and approved by the Review Board and Ethics Committee of National Cheng Kung University Hospital (IRB approval number: B-ER-113-266) and Chang Gung Memorial Hospital (IRB approval number: 202401496B0).

Treatment and treatment response evaluation

S-1 monotherapy was administered orally twice daily for 4 weeks in a 6-week cycle or for 2 weeks in a 3-week cycle, as determined by the physician. After the initiation of treatment, patients underwent chest CT scans every 12 weeks to assess tumor response. Brain MRI, whole-body bone scans or abdominal CT scans were performed based on physicians’ decision, or sooner if clinical symptoms indicated potential brain, bone or liver metastases. Objective tumor response in patients with measurable lesions was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and progression-free survival (PFS) was measured from the start of treatment until radiological progression, discontinuation due to adverse events (AEs), or death. The OS was measured from the start of treatment until the date of death. Cases with follow-up loss before the data cutoff date were treated as censored, using the last visit date as the censoring point. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Statistical analysis

Categorical variables are presented as counts and percentages, and were compared using Pearson χ² test or Fisher exact test, depending on the expected values. Both PFS and OS were estimated using the Kaplan-Meier method, which provides the interquartile range, and were compared using the log-rank test. To identify independent prognostic factors, univariate analysis was initially performed, and variables with significance were subsequently selected for inclusion in the multivariate Cox proportional hazards model All P-values in this study were 2-sided, with P < .05 considered statistically significant. Statistical analyses were conducted using SPSS software (IBM Corp Released 2011. IBM SPSS Statistics for Windows, version 20.0. Armonk, New York: IBM Corp). Survival curves were plotted using the survminer R package, which facilitates survival analysis and visualization. This study adheres to the ESMO-GROW¹² (Supplemental Table S1) and follows the STROBE statement¹³ (Supplemental Table S2) for reporting.

Results

Patient characteristics

Between July 1, 2012, and July 1, 2023, a total of 132 patients with advanced NSCLC were enrolled from NCKUH and Linkou CGMH. Patients at NCKUH were treated between July 1, 2012, and July 1, 2023, with the last follow-up in October 31, 2023, while those at Linkou CGMH were treated between February 1, 2020, and January 31, 2023, with the last follow-up on August 31, 2023. After excluding 31 patients who received treatment for less than 2 weeks, 101 lung cancer patients were included in the analysis. The median follow-up duration was 5.7 months (range: 0.7-39.3 months).

The baseline characteristics are summarized in Table 1. The median age was 65 years (range: 37-86 years). Of the 101 patients, 58 were men (57.4%). Most patients (93 patients, 92.1%) had stage IV disease upon enrollment. Most of the enrolled patients were histologically diagnosed with adenocarcinoma (69 patients, 68.3%), and the gene mutation was predominantly wild type (70 patients, 69.3%). The most common site of metastasis was the brain (28.7%). Thirty-six patients who were enrolled in the study received S-1 monotherapy as either first-line or second-line treatment. Prior to the administration of S-1 monotherapy, previous therapies included pemetrexed (62.4%), TKIs (36.6%), and ICI (26.7%). The baseline characteristics stratified by treatment line of S-1 therapy demonstrated similar distributions in age, sex, histology, disease stage, gene mutation status, presence of liver and brain metastases, and prior treatments with TKIs (Supplemental Table S3). Patients who received S-1 in the first-line or second-line setting had a lower incidence of adrenal metastasis, less prior pemetrexed treatment, and less exposure to immunotherapy.

Table 1.

Baseline characteristics.

Characteristics	All patients (N = 101)	(%)
Age (years), median (range)	65 (37-86)
⩽70	69	68.3
>70	32	31.7
Sex
Male	58	57.4
Female	43	42.6
Morphology
Adenocarcinoma	69	68.3
Non-adenocarcinoma	32	31.7
Stage
III	8	7.9
IV	93	92.1
Gene mutation
EGFR	29	28.7
BRAF	1	1.0
KRAS	1	1.0
Wild type	70	69.3
Liver metastasis
Yes	10	9.9
No	91	90.1
Brain metastasis
Yes	29	28.7
No	72	71.3
Adrenal metastasis
Yes	7	6.9
No	94	93.1
Previous therapy of pemetrexed
Yes	63	62.4
No	38	37.6
Previous therapy of TKI
Yes	37	36.6
No	64	63.4
Previous therapy of IO
Yes	27	26.7
No	74	73.3
Line of S-1 monotherapy
⩽2	36	35.6
⩾3	65	64.4

Abbreviations: EGFR, epidermal growth factor receptor; IO, immunotherapy; TKI, tyrosine kinase inhibitor.

Treatment efficacy and adverse effects

Among the 101 patients, 8 (7.9%) achieved a partial response (PR), and 36 (35.6%) had stable disease (SD). The overall response rate (ORR) was 7.9%, while the disease control rate (DCR) was 43.6% (Table 2). The median PFS was 2.6 months (95% CI: 2.2-3.1; Figure S1), and the median OS was 6.0 months (95% CI: 4.8-7.2, Figure S2). The median PFS and OS for patients achieving disease control (complete response [CR], PR, and SD) were significantly improved, with median PFS at 5.5 months (95% CI: 2.9-8.2, log-rank P < .0001; Figure S3) and median OS at 12.0 months (95% CI: 3.3-20.6, log-rank P < .0001; Figure S4), compared with patients with progressive disease. The overall incidence of AEs was 45.5%, with only 8% of patients experiencing adverse effects greater than grade 3 (Table 2).

Table 2.

Overall response rate and adverse events.

Characteristics	All patients	(%)
Response rate
PR	8	7.9
SD	36	35.6
PD	51	50.5
NA	6	5.9
Objective response rate
CR/PR	8	7.9
SD/PD/NA	93	92.1
Disease control rate
CR/PR/SD	44	43.6
PD/NA	57	56.4
Any adverse event
Grade 0	55	54.5
Grade 1	29	28.7
Grade 2	9	8.9
Grade 3	7	6.9
Grade 4	1	1.0

Abbreviations: CR, complete remission; PD, progressive disease; PR, partial response; SD, stable disease.

Efficacy and adverse effects across different lines of treatment

Patients receiving S-1 monotherapy as a first or second-line treatment exhibited significantly improved ORR (16.7% vs 3.1%, P = .023), DCR (61.1% vs 33.8%, P = .008), and PFS (4.2 months vs 2.3 months, P < .001) (Table 3, Figure 1) and extended OS (8.8 months vs 4.7 months, P = .07) (Figure S5) compared with those receiving it as a third-line or later treatment. The overall incidence of AEs and grade 3 or higher adverse effects did not differ between the 2 groups (Table 3).

Table 3.

Comparison of objective response rate (ORR), disease control rate (DCR), and adverse events in patients receiving S-1 monotherapy in first-line or second-line treatment versus those receiving it in third line or later.

Response	Line of S-1 monotherapy		P value
Response	⩽2(n = 36)	⩾3(n = 65)	P value
ORR			.023
CR/PR	6 (16.7)	2 (3.1%)
SD/PD/NA	30 (83.3)	63 (96.9)
DCR			.008
CR/PR/SD	22 (61.1)	22 (33.8)
PD/NA	14 (38.9)	43 (66.2)
Any adverse event			.081
Grade 0	25 (69.4)	30 (46.2)
Grade 1	7 (19.4)	22 (33.8)
Grade 2	1 (2.8)	8 (12.3)
Grade 3	2 (5.6)	5 (7.7)
Grade 4	1 (2.8)	0
Any adverse event ⩾ 3			>.999
No	33 (91.7)	60 (92.3)
Yes	3 (8.3)	5 (7.7)

Abbreviations: CR, complete remission; PD, progressive disease; PR, partial response; SD, stable disease.

Figure 1.

Progression-free survival of patients treated with S-1 monotherapy as first or second line versus third line or later.

Identification of prognostic factors

Univariate Cox proportional hazards regression analysis identified several significant prognostic factors for PFS, including histology, previous pemetrexed therapy, line of S-1 monotherapy, tumor response to treatment, and DCR. For OS, liver metastasis, brain metastasis, tumor response to treatment, and DCR were identified as significant prognostic factors (Supplemental Table S4). Multivariate Cox regression analysis of prognostic factors for PFS and OS included variables with P < .05 in the univariate Cox proportional hazards regression analysis. This analysis revealed that different lines of S-1 therapy (⩽2 vs ⩾3) were an independent predictor for PFS (hazard ratio 2.01, P = .014), and the absence of liver and brain metastasis was an independent predictor for OS (hazard ratio 2.01, P = .014) (Table 4).

Table 4.

Multivariate Cox regression analysis of prognostic factors in progression-free survival and overall survival.

Characteristics	Progression-free survival			Overall survival
Characteristics	Hazard ratio	95% C.I. of HR	P value	Hazard ratio	95% C.I. of HR	P value
Histology			.852	-
Adenocarcinoma (n = 69)	0.92	0.40-2.13
Non-adenocarcinoma (n = 32)	1
Liver metastasis
Yes (n = 10)	-			2.06	1.01-4.21	.046
No (n = 91)				1
Brain metastasis	-
Yes (n = 29)				2.04	1.27-3.28	.003
No (n = 72)				1
Previous therapy of pemetrexed				-
Yes (n = 63)	1.61	0.69-3.78	.272
No (n = 38)	1
Line of S-1 monotherapy				-
⩽2 (n = 36)	1
⩾3 (n = 65)	2.01	1.15-3.51	.014

Abbreviations: CI, confidence interval; HR, hazard ratio.

Discussion

This study is the first real-world investigation demonstrating the efficacy and safety of S-1 monotherapy in Taiwan. Patients with locally advanced stage III or stage IV lung cancer who received S-1 monotherapy, whether as an earlier-line or later-line treatment, achieved durable median ORR, DCR, PFS, and OS, with rates of 7.9%, 43.6%, 2.6 months, and 6.0 months, respectively, in the overall study population. Furthermore, patients who achieved disease control experienced significant benefits, with prolonged PFS (5.5 vs 1.7 months, 95% CI: 2.9-8.2, log-rank P < .0001) and OS (12.0 vs 3.7 months, 95% CI: 3.3-20.6, log-rank P < .0001). In patients receiving S-1 monotherapy as a second-line or later-line treatment for previously treated NSCLC, various prospective clinical trials have demonstrated comparable ORR (range: 7.1%-8.3%), PFS (range: 1.5-3.1 months), and OS (range: 7.6-12.8 months).^10,14
-16 S-1 monotherapy also has demonstrated promising ORR (range: 7.9%-22.6%), PFS (range: 4.4-5.5 months), and OS (range: 12.4-17 months) as a first-line therapy in prospective studies.^17,18 However, as these studies were all conducted in Japan, our study delivers real-world evidence supporting the role of S-1 in Taiwanese patients.

In most international guidelines, S-1 is not included in the standard treatment regimen,^19,20 and is sometimes regarded as a less effective treatment option, typically reserved for later-line therapy. However, our study found that when S-1 monotherapy was administered as a first-line or second-line treatment, it demonstrated more favorable ORR, PFS, DCR, and OS compared with its use as a third-line or later therapy. Multivariate Cox proportional hazards regression analysis identified the line of S-1 monotherapy (⩽ 2 vs ⩾ 3) as an independent predictor of PFS (hazard ratio: 2.01, 95% CI: 1.15-3.51, P = .014). A recent single-center study conducted in China demonstrated that S-1 monotherapy and combination therapy exhibited promising efficacy and good tolerability in advanced NSCLC, and the earlier treatment line was a positive prognostic factors for OS.²¹ The above findings highlight that S-1 serves as a viable alternative in frontline treatment for patients who are unable to tolerate the adverse effects of standard chemotherapy regimens while still providing promising clinical outcomes.

The one of anticancer mechanisms of S-1 targets thymidylate synthase (TS), similar to pemetrexed,²² which is often combined with platinum as the standard first-line treatment for patients with non-squamous NSCLC. Takemoto et al²³ reported concerns regarding cross-resistance and the limited efficacy of subsequent S-1 monotherapy in patients with non-squamous NSCLC who had previously received pemetrexed-containing chemotherapy, as observed in a retrospective multicenter study. In the East Asia S-1 trial, a subset analysis also suggested that the PFS of S-1 was inferior to that of docetaxel in previously treated adenocarcinoma patients who had received pemetrexed as a frontline regimen.¹⁰ Similarly, univariate analysis in our study identified the absence of prior pemetrexed therapy as a favorable prognostic factor for PFS but not for OS. These studies further support the notion that prior pemetrexed treatment may diminish the antitumor efficacy of S-1. Attending clinicians should take this into consideration and engage in shared decision-making with patients to carefully weigh the potential benefits and risks.

With the advancement of cancer treatment, the interaction of S-1 with chemotherapy, TKIs, or immunotherapy is being increasingly used in clinical practice. In the TCOG0701 CATS trial,²⁴ the combination therapy of S-1 and cisplatin demonstrated effectiveness that was noninferior to docetaxel plus cisplatin in terms of OS and PFS, while exhibiting a lower incidence of treatment-related AEs in previously untreated Japanese patients with stage IIIB or IV NSCLC. In the second-line or later-line setting, the combination of S-1 with docetaxel or paclitaxel has also been reported to demonstrate satisfactory efficacy with manageable toxicities.^15,25 The combination of S-1, carboplatin, and gefitinib has demonstrated effectiveness and tolerability as a first-line regimen for advanced NSCLC with EGFR mutations.²⁶ Anlotinib, a novel TKI approved in China in 2018 as a third-line treatment for refractory advanced NSCLC, exhibited promising efficacy and manageable toxicity when combined with S-1 in the third-line or later-line treatment of stage IV NSCLC.²⁷ Tamura et al²⁸ conducted a retrospective study evaluating the efficacy of S-1 following nivolumab compared with S-1 without prior ICI treatment, primarily in patients with advanced NSCLC. S-1 administered immediately after nivolumab demonstrated superior efficacy in treating advanced NSCLC compared with S-1 given at any line after nivolumab or without prior ICI exposure. This finding suggests a potential benefit of ICI priming effects, which may enhance the efficacy of subsequent cytotoxic chemotherapy. Despite several studies highlighting the potential role of S-1 combination therapy, most of these studies were non-randomized, involved small patient cohorts, or had a retrospective design. Therefore, larger, randomized trials are urgently warranted to validate these findings.

According to data from the SEER database in the United States, 47% of patients are above 70 years at the time of lung cancer diagnosis, and 14% are above 80 years. In addition, most cases are deemed inoperable at the time of diagnosis.²⁹ Older patients often have multiple comorbidities, reduced organ function, and are on various medications, which increases the risk of mortality and treatment-related toxicity compared with younger patients. Therefore, it is crucial to prioritize managing treatment toxicity, maintaining quality of life, and supporting physical activity in this vulnerable population. Two studies have found that pretreatment quality of life and physical activity are associated with survival outcomes in older patients.^30,31 A subgroup analysis of the EAST-LC Trial focusing on patients aged 70 years and older with pretreated advanced NSCLC revealed that S-1 monotherapy significantly prolonged OS (14.7 vs 12.1 months, hazard ratio: 0.76, 95% CI: 0.54-1.07) compared with docetaxel. In addition, S-1 monotherapy demonstrated a more favorable quality of life profile, as assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30).³² Therefore, particularly in older adult patients, strategies to maintain treatment while minimizing side effects and enhancing quality of life and functional status may potentially improve survival rates.³²

Metronomic chemotherapy involves the continuous administration of chemotherapeutic drugs at low doses, approximately 1/3 to 1/10 of the maximum tolerated dose (MTD), with no extended breaks in treatment. This approach offers advantages such as minimal side effects and a reduced risk of acquired drug resistance.³³ Compared with intravenous chemotherapy, S-1 may be considered somehow metronomic chemotherapy. The daily use provides the real-time adjustment for the patients experiencing AEs. For example, the patients can withhold S-1 once grade 2 AE occurs so grade 3 AE will not occur. Our findings support this perspective, as fewer than 10% of patients experienced grade 3 or higher AEs, which is particularly significant for older adult and vulnerable populations. Some clinical practitioners have expressed concerns about the elevated gastrointestinal toxicity of S-1, particularly in Western patients. However, this observation is somewhat anecdotal, based on a small study involving Asians (N = 18) and Caucasians (N = 19).^34,35 For those experiencing adverse effects, a 3-week cycle of S-1 administered on days 1 to 14, followed by a 1-week break, has been reported to be more manageable.³⁶ This contrasts with the EAST-LC trial schedule, where S-1 was administered daily from days 1 to 28, followed by a 2-week break in a 6-week cycle.¹⁰

Indeed, this study has several limitations. First, it is a retrospective study. Second, patients receiving S-1 monotherapy as a first-line or second-line treatment had a lower incidence of adrenal metastasis, potentially introducing selection bias, though univariate analysis showed adrenal metastasis was not a prognostic factor for PFS or OS. Third, a higher proportion of patients in the third-line or later-line setting had prior pemetrexed treatment, which may have attenuated S-1 efficacy. Univariate analysis confirmed prior pemetrexed as a poor prognostic factor for PFS but not for OS. The difference in prior pemetrexed treatment was likely attributed to the higher proportion of adenocarcinoma patients in the later-line treatment setting. Fourth, performance status data were not presented due to potential inaccuracies in medical records, as updates are infrequent for later-line treatments. Fifth, patients receiving S-1 monotherapy in the first-line or second-line setting had less prior immunotherapy exposure, though univariate analysis found it was not a prognostic factor for PFS or OS. Finally, as data collection spanned over a decade, some earlier patients did not receive ICIs before S-1 monotherapy. Therefore, further research is needed to confirm the efficacy of S-1 monotherapy following ICI treatment.

Conclusion

This study confirms that S-1 monotherapy improves DCR, prolongs PFS, and extends OS in a real-world setting, regardless of patient age, histological subtype, gene mutation status, or prior treatment with TKIs or immunotherapy. The treatment was generally well tolerated, with mostly low-grade and manageable toxicities. Notably, S-1 monotherapy demonstrated greater efficacy when used as a first-line or second-line treatment compared with later lines, suggesting its potential as an alternative for patients who cannot tolerate standard upfront chemotherapy. Further studies are needed to validate these findings and explore the potential benefits of combining S-1 with platinum-based chemotherapy, targeted therapy, or immunotherapy.

Supplemental Material

sj-docx-1-onc-10.1177_11795549251348367 – Supplemental material for Real-World Efficacy and Safety of S-1 Monotherapy in Non-Small Cell Lung Cancer Management: Insights From a Multicenter Retrospective Cohort Study

Supplemental material, sj-docx-1-onc-10.1177_11795549251348367 for Real-World Efficacy and Safety of S-1 Monotherapy in Non-Small Cell Lung Cancer Management: Insights From a Multicenter Retrospective Cohort Study by I-Lin Tsai, Chien-Yu Lin, Po-Lan Su, Chien-Chung Lin, John Wen-Cheng Chang, Chen-Yang Huang, Yueh-Fu Fang, Ching-Fu Chang, Chih-Hsi Scott Kuo, Ping-Chih Hsu, Cheng-Ta Yang and Chiao-En Wu in Clinical Medicine Insights: Oncology

Footnotes

Acknowledgements

Not applicable

ORCID iDs

I-Lin Tsai

Chiao-En Wu

Ethics Considerations

This study was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Local ethical approval was obtained from the Ethics Committee of the National Cheng Kung University Hospital (IRB approval number: B-ER-113-266) and the Ethics Committee of Chang Gung Memorial Hospital (IRB approval number: 202401496B0). Both of the institutional ethics review boards approved the study design, and the informed consent was not applicable due to study design.

Consent to Participate

The requirement for informed consent for this study was waived by the Review Board and Ethics Committee of National Cheng Kung University Hospital and Chang Gung Memorial Hospital.

Author Contributions

I-Lin Tsai: Acquisition and interpretation of data; Drafted the article and revised it critically for important intellectual content

Chien-Yu Lin: Acquisition, analysis and interpretation of data; Drafted the article and revised it critically for important intellectual content

Po-Lan Su: Made a substantial contribution to the concept or design of the work; analysis and interpretation of data

Chien-Chung Lin: Made a substantial contribution to the concept or design of the work; analysis and interpretation of data

John Wen-Cheng Chang: Acquisition and analysis of data

Chen-Yang Huang: Analysis and interpretation of data

Yueh-Fu Fang: Analysis and interpretation of data

Ching-Fu Chang: Acquisition, analysis and interpretation of data

Chih-Hsi Scott Kuo: Acquisition, analysis and interpretation of data

Ping-Chih Hsu: Acquisition, analysis and interpretation of data; revised it critically for important intellectual content

Cheng-Ta Yang: Acquisition, analysis and interpretation of data; revised it critically for important intellectual content

Chiao-En Wu: Made a substantial contribution to the concept or design of the work; acquisition, analysis and interpretation of data; Approved the version to be published

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.

Supplemental Material

Supplemental material for this article is available online.

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