Doxorubicin paclitaxel in pretreated advanced small-cell lung cancer: a large real-life retrospective study

Introduction

Lung cancer remains the leading cause of cancer-related mortality worldwide (1). Small-cell lung cancer (SCLC) represents about 15% of all lung cancer cases and is characterized by an aggressive course and poor prognosis (2). Immune checkpoint inhibitors (ICI) and targeted therapies have revolutionized the management of non-SCLC (3-6). However, limited progress has been made in the treatment of extensive SCLC over the past three decades, with platinum-etoposide regimens remaining the mainstay of therapy (7). Since 2018, the addition of ICI to first-line platinum-etoposide chemotherapy demonstrated a significant, though modest, benefit in overall survival (OS) for advanced-stage SCLC (8,9).

While SCLC initially responds well to chemotherapy, the majority of patients relapse in less than six months. For many years, second-line treatment was determined by the treatment-free interval (TFI) and the previous efficacy of first-line platinum-based chemotherapy (7). Platinum-etoposide re-administration used to be recommended for platinum-sensitive SCLC (TFI ≥3 months), due to its elevated objective response rate (ORR) of 49% and its correlation with improved clinical efficacy relative to other cytotoxic treatment protocols (10). In contrast, for platinum-refractory cases (progression occurring during platinum-based therapy) or platinum-resistant disease (TFI <3 months), prognosis remains poor, as second-line cytotoxic agents elicit an ORR of around 15% (7). In this clinical context, topotecan long remained the reference standard, as it has been shown to prolong OS compared to best supportive care (11). However, its clinical application is often constrained by severe and frequent hematological toxicities, coupled with only relatively limited therapeutic benefit (12). In a phase III randomized trial, the anthracycline-based CAV regimen (cyclophosphamide, adriamycin, vincristine) exhibited comparable efficacy to that of topotecan (13). Similarly, a randomized phase III trial comparing amrubicin with topotecan as second-line therapy for SCLC (14) did not demonstrate an OS benefit, further highlighting the limited progress with cytotoxic regimens in this setting.

In 2020, lurbinectedin demonstrated an ORR of 22.2% in the second-line setting of platinum-resistant extensive SCLC (15); however, combining it with doxorubicin did not result in a significant improvement in OS compared to topotecan (16). Furthermore, various investigational approaches for subsequent therapy, including rovalpituzumab-tesirine (17), nivolumab (18), and nivolumab-ipilimumab (19), have not yielded improvements in patient outcomes. This highlights a persistent gap in current therapeutic strategies. In fact, two phase III trials published in 2025 have reshaped the treatment landscape. The DeLLphi-304 study compared the DLL3-targeted bispecific T-cell engager tarlatamab to standard chemotherapy in patients with relapsed SCLC after platinum-based therapy, demonstrating a significant OS benefit (20). In parallel, the IMforte trial evaluated maintenance therapy with lurbinectedin plus atezolizumab versus atezolizumab alone following induction platinum-etoposide-atezolizumab in extensive-stage SCLC, and also reported a significant OS improvement (21). These landmark trials are very recent and are in the process of being incorporated into clinical practice, establishing both strategies as emerging new standards of care.

Paclitaxel, a taxane-class spindle poison, has been evaluated in pretreated advanced SCLC, demonstrating ORRs of approximately 20–30% in phase II clinical trials, with an acceptable safety profile (22,23). Additionally, a phase II trial published in 2000 assessed the combination of paclitaxel with doxorubicin in patients with relapsed SCLC, reporting a promising ORR of 41% (24). However, this combination has not been widely adopted in routine medical use, and evidence regarding its therapeutic effectiveness and safety profile remains scarce.

In this real-world study, we aim to present our institutional experience with the administration of doxorubicin-paclitaxel use in pre-treated SCLC. Our objective was to evaluate the clinical outcomes and safety of this combination in pretreated patients with extensive-stage SCLC at the Gabriel-Montpied University Hospital Center in Clermont-Ferrand, France. Additionally, we examined patient and tumor-related factors linked to PFS and OS duration using multivariate analysis. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-653/rc).

Methods

Study design and patients

Clinical data were retrospectively retrieved for all consecutive patients with histologically confirmed SCLC who were treated with the paclitaxel-doxorubicin regimen between 2000 and 2024 at the Department of Medical Oncology, Gabriel-Montpied University Hospital Center, Clermont-Ferrand, France. Other eligibility criteria were: ≥18-year-old, ≥1 prior platinum etoposide-based chemotherapy line, and ≥1 fully administered cycle of paclitaxel doxorubicin. Patients with a concurrent other antitumor therapy, or followed in another care center for their cancer, were excluded.

Study treatment

Paclitaxel (175 mg/m²) and doxorubicin (40 mg/m²) were administered intravenously every 3 weeks for a maximum of 6 courses. Discontinuation of treatment occurred due to progression of disease, severe toxicity, deterioration in performance status (PS), or based on clinical judgment.

Endpoints

The primary endpoint was the PFS. PFS was characterized as the time between the initiation of the treatment of interest (TOI) and tumor progression [Response Evaluation Criteria in Solid Tumors (RECIST) or not-RECIST radiological progression, clinical progression: based on physician assessment] or death. Secondary endpoints included safety and OS. OS was characterized as the interval from initiation of the TOI and death. For the safety evaluation, due to the retrospective design of the study, we restricted the documentation of adverse events to those leading to dose reduction or interruption of treatment. Moreover, clinical and tumor-related features linked to PFS and OS duration were explored using both univariate and multivariate analytical approaches.

Statistical analysis

Descriptive statistics were used to summarize the study population: categorical variables were reported as counts and percentages, while continuous variables were described using medians and interquartile ranges (IQR). PFS and OS were estimated using Kaplan-Meier methodology. For survival analyses, censoring occurred at the date of last database entry or the point of loss to follow-up. The duration of follow-up was estimated using the reverse Kaplan-Meier method, considering death as a censoring event and censoring as the event of interest. In addition, a simple calculation of follow-up (from treatment initiation to last contact or death) was performed to provide a descriptive median duration. Correlations between clinical or tumor characteristics and survival outcomes (PFS, OS) were quantified using hazard ratios (HRs) with 95% confidence intervals (95% CIs), derived from Cox proportional hazards regression in both univariable and multivariable contexts. Multivariable modeling was performed via a stepwise selection algorithm. Variables with a P value ≤0.2 in univariable analysis were considered for entry into the multivariable model. Both forward and backward selection procedures were applied to ensure robustness and consistency of the final model. All statistical analyses were performed using R software, version 4.1.3.

Ethics statement

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the Clinical Research and Innovation Department of Clermont-Ferrand University Hospital (IRB00013412, Clermont-Ferrand University Hospital IRB #1, approval No. 2024-CF367). Informed consent was not required under French regulations for this type of retrospective study. Instead, all living patients received an information and non-objection note and a letter explaining the research project. The files of the deceased patients who do not stipulate a refusal to use their healthcare data will be used without any further steps. Patients’ clinical records were retrospectively gathered from electronic files using a de-identified form.

Results

Patient characteristics

A total of 189 patients were identified through the local database. Of these, 40 were excluded for the following reasons: no pathologically confirmed SCLC (n=23), follow-up at another care center (n=12), no prior EP chemotherapy (n=5) (Figure 1, flow chart). This resulted in a final cohort of 149 patients. Among the patients, 100 (67.1%) were male, with a median age of 63 years (range: 42–88). A total of 118 patients (79.2%) had an Eastern Cooperative Oncology Group PS (ECOG PS) of 0 or 1. Most patients (115, 77.2%) were diagnosed at the metastatic stage. Platinum rechallenges had been administered to 53 patients (35.6%), while 29 (19.5%) had received ICI. At the initiation of the TOI, 64 patients (43%) had brain metastases. The median line of systemic treatment at TOI initiation was 2.1 (range: 2–4), and 30 patients (20.1%) were platinum-sensitive. The patients’ characteristics are presented in Table 1.

Figure 1 Flow chart. EP, etoposide-platinum; SCLC, small-cell lung cancer.

Efficacy

Using the reverse Kaplan-Meier method, the median follow-up was not reached (NR). Based on the simple calculation method, the median follow-up duration was 5.1 months (95% CI: 0.6–16.1). The median PFS in the overall population was 2.4 months (95% CI: 2.1–3.8) (Figure 2A), with a median of 4.0 months (95% CI: 2.4–5.7) in the platinum-sensitive group and 2.2 months (95% CI: 2.1–3.5) in the platinum-resistant/refractory group (HR =1.42, 95% CI: 0.94–2.13, P=0.09) (Figure 2B). The median OS was 5.1 months (95% CI: 4.7–6.0) (Figure 3A), with a median of 6.1 months (95% CI: 5.1–9.8) in the platinum-sensitive group and 4.9 months (95% CI: 4.3–5.8) in the platinum-resistant/refractory group (HR =1.43, 95% CI: 0.95–2.16, P=0.08) (Figure 3B).

Figure 2 PFS—(A) in the overall population; (B) according to platinum-sensitivity. PFS was defined as the time from treatment initiation to tumor progression or death. Survival was estimated using Kaplan-Meier methodology, with censoring at last database entry or loss to follow-up. Platinum sensitivity was defined as a TFI ≥3 months after first-line platinum-based chemotherapy, while refractory/resistant disease was defined as progression during therapy or within 3 months of completion. CI, confidence interval; HR, hazard ratio; mPFS, median progression-free survival; TFI, treatment-free interval.

Figure 3 OS—(A) in the overall population; (B) according to platinum-sensitivity. OS was defined as the time from treatment initiation to death. Survival outcomes were estimated using Kaplan-Meier methodology, with censoring at the last database entry or at loss to follow-up. CI, confidence interval; HR, hazard ratio; mOS, median overall survival.

In univariate analysis, an ECOG PS of 2–4 (compared to 0–1) (HR =1.94, 95% CI: 1.28–2.95, P=0.002), the presence of carcinomatous meningitis (HR =8.98, 95% CI: 2.06–39.09, P<0.001), and the presence of liver metastasis (HR =1.61, 95% CI: 1.14–2.27, P=0.007) were associated with shorter PFS. In univariate analysis, an ECOG PS of 2–4 (compared to 0–1) (HR =2.93, 95% CI: 1.9–4.51, P<0.001), the presence of carcinomatous meningitis (HR =11.1, 95% CI: 2.5–49.25, P<0.001), and the presence of liver metastasis (HR =1.75, 95% CI: 1.24–2.45, P=0.001) were associated with shorter OS. Of note, in the univariate analysis, neither prior treatment with ICI (PFS: HR =1.15, 95% CI: 0.76–1.74, P=0.53; OS: HR =0.94, 95% CI: 0.68–1.53, P=0.94) nor the TOI line number (2 vs. ≥3; PFS: HR =1.18, 95% CI: 0.63–2.18, P=0.61; OS: HR =1.05, 95% CI: 0.57–1.96, P=0.87) was associated with a significant change in survival outcomes.

In multivariate analysis, an ECOG PS of 2–4 (compared to 0–1) was associated with shorter PFS (HR =1.9, 95% CI: 1.22–2.8, P=0.004) (Figure 4A) and OS (HR =2.73, 95% CI: 1.76–4.2, P<0.001) (Figure 4B). Best overall response was not assessable in 30 patients (20.1%). In the overall population (n=149), the ORR was 22.2% including non-evaluable patients, and 27.7% when excluding them. The disease control rate (DCR) was 41.6% including non-evaluable patients, and 52.1% when excluding them. Among platinum-sensitive patients (n=30), the ORR was 43.3% including non-evaluable patients, and 50.0% when excluding them. The DCR was 63.3% including non-evaluable patients, and 72.4% when excluding them. In the platinum-resistant/refractory group (n=119), the ORR was 16.8% including non-evaluable patients, and 21.5% when excluding them. The DCR was 36.1% including non-evaluable patients, and 46.1% when excluding them. A summary of efficacy outcomes is presented in Table 2.

Figure 4 Multivariable analysis of clinical and tumor-related factors associated with PFS (A) and OS (B). HRs with 95% CIs were estimated using Cox proportional hazards models, with variable selection performed via a stepwise algorithm. PFS was defined as the time from treatment initiation to tumor progression or death, and OS as the time from treatment initiation to death. Both were estimated using Kaplan-Meier methodology. **, P<0.01; ***, P<0.001. AIC, Akaike information criterion; CI, confidence interval; ECOG_cat, Eastern Cooperative Oncology Group Performance Status category; HR, hazard ratio; L1-CT, first line chemotherapy; OS, overall survival; PFS, progression-free survival.

After discontinuing doxorubicin-paclitaxel, 77 patients (51.7%) received at least one subsequent systemic therapy, including 27 (18.1%) with multiple lines (range 2–5). The most common regimens immediately after the TOI were topotecan (n=55), gemcitabine (n=15), lurbinectedin (n=3), platinum-etoposide rechallenge (n=2), and epirubicin-ifosfamide (n=2).

Safety profile

Adverse events resulted in dose reduction for 73 (54.9%) patients. The main causes of dose reduction were general alteration (34, 59.6%), hematotoxicity (11, 19.3%), and peripheral neuropathy (11, 19.3%). Treatment discontinuation due to adverse events occurred in 14 (9.5%) patients. No toxic death was reported. Safety analysis is detailed in Table 3.

Discussion

This retrospective study aimed to assess both the therapeutic activity and the toxicity profile of the doxorubicin-paclitaxel regimen in previously treated SCLC patients. In this cohort of 149 unselected patients, this chemotherapy combination showed some activity for pretreated SCLC in terms of PFS, OS, ORR and DCR with a safety profile that appeared generally manageable, although toxicity may still be a limiting factor in this frail population.

It is noteworthy that topotecan remains the sole agent to have shown a statistically significant OS benefit over best supportive care in the second-line treatment of extensive SCLC, as evidenced by a Phase III randomized trial (11). A comparative study evaluating topotecan versus the CAV regimen in relapsed platinum-sensitive SCLC reported comparable ORR and OS between both treatment groups (13). Multiple Phase II studies assessing single-agent chemotherapy, such as paclitaxel, in previously treated SCLC have demonstrated promising yet markedly variable clinical outcomes (23,25,26). More recently, two phase III trials have reshaped the therapeutic landscape: the DeLLphi-304 study evaluating tarlatamab in SCLC after platinum-based chemotherapy (20), and the IMforte trial assessing lurbinectedin plus atezolizumab as first-line maintenance in extensive-stage SCLC (21). Both strategies demonstrated a significant OS benefit and have established themselves as new standards of care for patients with extensive-stage SCLC previously treated with platinum-ICI regimens.

This retrospective analysis encompassed an unselected patient population presenting multiple adverse prognostic indicators, including poor PS (20.8% with PS ≥2), central nervous system metastases (43.6%), and platinum-resistant or refractory disease progression (79.9%). Despite these adverse features, the doxorubicin-paclitaxel regimen exhibited clinical activity in pretreated SCLC, with a median PFS of 2.4 months and an ORR of 27.7%. Moreover, the ORR of 21.5% and DCR of 46.1% observed in the platinum-resistant/refractory subgroup appear higher than those historically reported with treatments such as topotecan or CAV (13,14). In addition, the tolerability was considered manageable and aligned with prior studies evaluating this chemotherapy protocol. We observed notable neurotoxicity and hematologic side effects that resulted in a substantial frequency of dose reductions (54.9%). However, these adverse effects were controllable, and no fatalities related to treatment were reported. In the phase II study by Sonpavde et al. of the paclitaxel-doxorubicin combination, the median PFS was 14 weeks, and the median OS was 25 weeks (24). In comparison, our cohort showed shorter PFS and OS, which may be attributed to a less selected population with a higher prevalence of poor prognostic factors. A more recent French real-world study evaluating another paclitaxel-anthracycline regimen (paclitaxel-epirubicin) in patients with relapsed SCLC reported similar efficacy, with a median PFS of 11.0 weeks, a median OS of 23 weeks, and an ORR of 34.5% (27). The combination of doxorubicin and paclitaxel is not recommended in major international guidelines, such as the National Comprehensive Cancer Network, for relapsed SCLC. Its use in our cohort reflects a historical institutional practice adopted after a phase II trial reported promising activity (24). Our study provides real-world evidence on this regimen in pretreated extensive-stage SCLC, including the difficult platinum-resistant setting. Furthermore, our study confirmed the already well-established role of poor PS as a negative prognostic factor, with ECOG PS 2–4 versus 0–1 associated with shorter PFS (HR =1.9, 95% CI: 1.22–2.8) and OS (HR =2.73, 95% CI: 1.76–4.2). Beyond statistical significance, these HRs also exceed the recently proposed minimal clinically important difference thresholds for effect sizes other than mean differences (28), underscoring the strong clinical as well as statistical relevance of PS in this setting.

This study presents several limitations, primarily stemming from its retrospective design and single-center setting. Objective radiological response could be assessed in only 119 patients, representing 79.9% of the cohort. There was also substantial variability among patients regarding the types of prior chemotherapy regimens received. Considering the heterogeneity of the patient population and the use of different prior treatment regimens, the study cohort may not reflect the clinical profile of a standard SCLC patient. Nevertheless, we acknowledge the limitations of our study, and additional prospective and comparative research is required to assess the therapeutic value of this approach.

Conclusions

To the best of our knowledge, this is the first study to present real-world evidence on the use of the paclitaxel-doxorubicin combination in previously treated SCLC patients. Our findings indicate that this regimen may offer therapeutic benefit in this context. Nonetheless, the significant toxicity associated with the combination underscores the importance of meticulous patient selection. Prospective comparative studies are warranted to better define its role in the therapeutic landscape of advanced SCLC.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-653/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-653/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-653/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-653/coif). P.G. reports consulting fees for BMS, academic grant from Sanofi and travel accommodation by Eisai. L.C. reports payment or honoraria for lectures or presentations from AAA, Amgen, Astellas, Bayer, BMS, Eisai, Ipsen, Janssen, MSD, and Pfizer; and travel accommodation from Pfizer, Janssen, Bayer, and Ipsen. C.B. reports payment or honoraria for lectures or presentations from SANOFI, and travel accommodation from AXAIR, ORKYN, MSD, and Boehringer. C.R.D. reports payment or honoraria for lectures or presentations from Asten, Menarini, Laboratoire GlaxoSmithKline, Astra-zeneca, and Sanofi, and travel accommodation from Asten, and Sanofi. B.A. has received research Grants from MSD Avenir; consulting fees from Novartis, Astellas, Sanofi, AstraZeneca, BMS, and MSD; and travel accommodation from Janssen, MSD, Pfizer, IPSEN Pharma, Bayer, and Takeda. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the Clinical Research and Innovation Department of Clermont-Ferrand University Hospital (IRB00013412, Clermont-Ferrand university hospital IRB #1, approval number 2024-CF367). Informed consent was not required under French regulations for this type of retrospective study. Instead, all living patients received an information letter and a non-objection statement regarding the research project, while data from deceased patients could be used unless a prior refusal had been recorded.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. [Crossref] [PubMed]
2. Rudin CM, Brambilla E, Faivre-Finn C, et al. Small-cell lung cancer. Nat Rev Dis Primers 2021;7:3. [Crossref] [PubMed]
3. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2017;377:829-38. [Crossref] [PubMed]
4. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2018;378:113-25. [Crossref] [PubMed]
5. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 2015;373:1627-39. [Crossref] [PubMed]
6. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2016;375:1823-33. [Crossref] [PubMed]
7. Dingemans AC, Früh M, Ardizzoni A, et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol 2021;32:839-53. [Crossref] [PubMed]
8. Horn L, Mansfield AS, Szczęsna A, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med 2018;379:2220-9. [Crossref] [PubMed]
9. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet 2019;394:1929-39. [Crossref] [PubMed]
10. Baize N, Monnet I, Greillier L, et al. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 2020;21:1224-33. [Crossref] [PubMed]
11. O'Brien ME, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 2006;24:5441-7. [Crossref] [PubMed]
12. Eckardt JR, von Pawel J, Pujol JL, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 2007;25:2086-92. [Crossref] [PubMed]
13. von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999;17:658-67. [Crossref] [PubMed]
14. von Pawel J, Jotte R, Spigel DR, et al. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol 2014;32:4012-9. [Crossref] [PubMed]
15. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol 2020;21:645-54. [Crossref] [PubMed]
16. Paz-Ares L, Ciuleanu T, Navarro A, et al. PL02.03 Lurbinectedin/Doxorubicin versus CAV or Topotecan in Relapsed SCLC Patients: Phase III Randomized ATLANTIS Trial. J Thorac Oncol 2021;16:S844-5.
17. Uprety D, Remon J, Adjei AA. All That Glitters Is Not Gold: The Story of Rovalpituzumab Tesirine in SCLC. J Thorac Oncol 2021;16:1429-33. [Crossref] [PubMed]
18. Spigel DR, Vicente D, Ciuleanu TE, et al. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331 Ann Oncol 2021;32:631-41. [Crossref] [PubMed]
19. Owonikoko TK, Park K, Govindan R, et al. Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451. J Clin Oncol 2021;39:1349-59. [Crossref] [PubMed]
20. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy. N Engl J Med 2025;393:349-61. [Crossref] [PubMed]
21. Paz-Ares L, Borghaei H, Liu SV, et al. Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial. Lancet 2025;405:2129-43. [Crossref] [PubMed]
22. von Eiff D, Bozorgmehr F, Chung I, et al. Paclitaxel for treatment of advanced small cell lung cancer (SCLC): a retrospective study of 185 patients. J Thorac Dis 2020;12:782-93. [Crossref] [PubMed]
23. Yamamoto N, Tsurutani J, Yoshimura N, et al. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res 2006;26:777-81.
24. Sonpavde G, Ansari R, Walker P, et al. Phase II study of doxorubicin and paclitaxel as second-line chemotherapy of small-cell lung cancer: a Hoosier Oncology Group Trial. Am J Clin Oncol 2000;23:68-70. [Crossref] [PubMed]
25. Masters GA, Declerck L, Blanke C, et al. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol 2003;21:1550-5. [Crossref] [PubMed]
26. Zugazagoitia J, Paz-Ares L. Extensive-Stage Small-Cell Lung Cancer: First-Line and Second-Line Treatment Options. J Clin Oncol 2022;40:671-80. [Crossref] [PubMed]
27. Annic J, Babey H, Corre R, et al. Real‐life second‐line epirubicin-paclitaxel regimen as treatment of relapsed small‐cell lung cancer: EpiTax study. Cancer Med 2023;12:2658-65. [Crossref] [PubMed]
28. Horita N, Yamamoto S, Mizuki Y, et al. Minimal Clinically Important Difference (MCID) of Effect Sizes other than Mean Difference. J Clin Quest 2024;1:116-27.