The efficacy and safety of nab-paclitaxel plus anlotinib in small-cell Lung Cancer for third- line therapy

doi:10.21203/rs.3.rs-4725199/v1

Download PDF

Article

The efficacy and safety of nab-paclitaxel plus anlotinib in small-cell Lung Cancer for third- line therapy

https://doi.org/10.21203/rs.3.rs-4725199/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background: Small-cell lung cancer (SCLC) has a poor prognosis after failure of second-line therapy. This study investigated the efficacy and safety of nab-paclitaxel plus anlotinib as a third-line treatment for recurrent SCLC.

Methods: In this retrospective study, patients with recurrent SCLC with disease progression after two chemotherapeutic regimens were enrolled. Patients were randomized to one of two groups. One group (ANLIB) received 12 mg of anlotinib daily for 14 days until disease progression or unacceptable toxicity. The other group (ANNAB) received 260mg/m² of nab-paclitaxel on day 1 in combination with 12mg/d of anlotinib for 14 days. The ANNAB regimen was repeated every three weeks for up to 6 cycles, followed by maintenance with anlotinib until disease progression or unacceptable toxicity. The primary endpoints were progression-free survival (PFS) and overall survival (OS).

Results: Between January 1, 2021 and July 31, 2022, 48 patients were enrolled in this study and were randomly assigned to either the ANNAB or ANLIB group. The overall response rate (ORR) was significantly higher in the ANNAB group compared to the ANLIB group (37.5% vs. 8.3%, Fisher's exact test p = 0.0363). The median PFS was 6.0 months in the ANNAB group and 4.7 months in the ANLIB group (p = 0.0004). The median OS was 10.0 months in the ANNAB group compared with 7.3 months in the ANLIB group (p < 0.0001).

Conclusions: The combined-modality therapy of nab-paclitaxel and anlotinib as a third-line treatment for recurrent SCLC represents a promising therapeutic strategy with an acceptable toxicity profile.

Biological sciences/Cancer

Health sciences/Medical research

Health sciences/Oncology

small-cell lung cancer

nab-paclitaxel

anlotinib

third-line therapy

efficacy

safety.

Small-cell lung cancer (SCLC) accounts for approximately 13–15% of newly diagnosed lung cancer cases worldwide. It is considered an aggressive disease with a poor prognosis^[1]. About 70% of patients present with extensive-stage SCLC (ED-SCLC), which is associated with significantly worse survival outcomes compared to limited-stage disease^[2]. The standard first-line therapy for SCLC, consisting of platinum-based chemotherapy combined with etoposide, has remained unchanged for the past three decades and results in a median overall survival (OS) of about 10 months ^[2]. Although the introduction of atezolizumab and durvalumab into the first-line treatment regimen for ED-SCLC has led to a two-month improvement in median OS^{[3, 4]}, the overall prognosis remains unsatisfactory.

There is significant heterogeneity in second-line treatment recommendations across different countries. For example, topotecan is commonly used in Europe and North America^[5], while amrubicin is preferred in Japan ^[6]. Despite the variation in approved regimens for second-line therapy, the low response rates result in short relief periods. There are currently no standardized third-line systemic therapies available. However, anlotinib was approved as a third-line treatment by the National Medical Products Administration (NMPA) in 2019 based on the ALTER 1202 study, demonstrating improved progression-free survival (PFS) and overall survival (OS) ^[7].

While the ALTER 1202 study demonstrated an overall response rate (ORR) of 4.9% for anlotinib, the limited survival data may not be sufficient for patients with a good performance status (ECOG PS 0–1). Nanoparticle albumin-bound (nab)-paclitaxel, a new solvent-free formulation of paclitaxel, has shown promise in treating relapsed SCLC in some retrospective studies^{[8, 9]}. Although a prospective phase 2 study demonstrated some efficacy of nab-paclitaxel monotherapy in relapsed SCLC, the overall outcome remained unsatisfactory^[10]. Notably, there is a lack of data regarding the combined-modality treatment of anlotinib and nab-paclitaxel (ANNAB) for relapsed SCLC patients. In this retrospective study, we aimed to investigate the efficacy and safety of the ANNAB regimen as a third-line treatment for patients diagnosed with relapsed SCLC.

Patients

From January 1, 2021 to July 31, 2022, Binzhou Medical University Hospital enrolled patients aged 18 to 75 with a pathologically confirmed diagnosis of SCLC for this study. The key inclusion criteria were histologically or cytologically confirmed SCLC with disease progression after receiving second-line chemotherapy. Patients must have received a first-line treatment of platinum-based therapy plus etoposide and a second-line treatment of irinotecan. Additionally, they needed to have an ECOG PS of 0–1 at enrollment^[11] and measurable lesions based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, with a minimum interval of 3 weeks between the second and third-line treatments^[12]. Besides, to be eligible for this study, patients needed to have well-functioning bone marrow (hemoglobin ≥ 9.0g/L, absolute neutrophil count ≥ 1.5×10⁹/×L, platelet count ≥ 90×10⁹/×L, WBC count ≥ 3.0×10⁹/×L), liver function (total bilirubin ≤ 2.0mg/dL, albumin ≥ 35g/L, aspartate and alanine transaminase ≤ 2 times the upper limit of normal (ULN), ≤ 3 times ULN with liver metastases), kidneys function (serum creatinine ≤ 1.5mg/dL). Asymptomatic or controlled brain metastases were also included. Patients who had previously received anti-angiogenic agents, uncontrolled hypertension (blood pressure ≥ 160/100mmHg), risk of bleeding due to tumors near major blood vessels, uncontrolled serious medical conditions (e.g., unstable angina), or intolerance to nab-paclitaxel or anlotinib were excluded. This study adhered to the ethical guidelines set forth by the Binzhou Medical University Hospital Ethics Committee. All procedures involving human subjects were conducted in accordance with the Declaration of Helsinki and its amendments. Written informed consent was obtained from all participants prior to study enrollment. Primary chemotherapy resistance was defined as disease progression during or within 90 days of completing first-line platinum-based treatment. Conversely, primary chemotherapy sensitivity was defined as disease progression at least 90 days after finishing first-line treatment.

Treatment schedule

All patients in both groups received 12mg of anlotinib orally once daily for 14 days of a 21-day cycle. In the ANNAB group, patients additionally received a 30-minute intravenous infusion of 260mg/m² nab-paclitaxel on day 1 every 3 weeks. Treatment continued until disease progression or unacceptable toxicity. Following the initial 6 cycles of either the ANNAB or ANLIB regimen, patients who demonstrated a positive response on radiological assessment were eligible to continue receiving anlotinib monotherapy until disease progression or treatment intolerance. Dose modifications for anlotinib were implemented by the attending physician when necessary, following the protocol-defined criteria established for the study drugs. The National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0) guided the evaluation and management of any adverse events experienced by the patients. In accordance with guidelines set forth by the American Society of Clinical Oncology, the use of white blood cell growth factors for primary prophylaxis was not permitted in this study^[13].

Evaluations

Upon confirmation of relapse or disease progression, patients underwent comprehensive restaging using enhanced computed tomography (CT) scans of the neck, chest, and abdomen, brain-enhanced magnetic resonance imaging (MRI), and bone emission computed tomography (ECT). Radiological assessments using RECIST v1.1 criteria were conducted for all patients every two treatment cycles to monitor disease response. Two experienced physicians independently reviewed the imaging data for tumor assessment. In cases of discrepancy, a third, more senior physician acted as an adjudicator to reach a final consensus. Patients underwent comprehensive safety monitoring throughout the study. This included recording and evaluation of adverse events, laboratory tests, and physical examinations conducted every cycle.

Outcomes

Tumor response was categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The primary objective of the study was to evaluate PFS defined as the time from the first treatment to disease progression or death from any cause. OS was also assessed, defined as the time from the first treatment to death or the last follow-up visit. Secondary objectives included ORR, defined as the proportion of patients achieving CR or PR; disease control rate (DCR), defined as the proportion of patients achieving CR, PR, or SD; and evaluation of adverse events (AEs).

Statistical analysis

Data analysis was performed using GraphPad Prism version 10.1. Categorical variables were described using frequencies and percentages. The Fisher's exact test was used to compare categorical variables such as sex, disease stage, and ECOG score between groups. OS and PFS were estimated using the Kaplan-Meier method. A p-value of less than 0.05 was statistically significant.

Between January 1, 2021 and July 31, 2022, we retrospectively enrolled 48 patients pathologically confirmed with SCLC in our study. Patients were enrolled consecutively upon meeting the inclusion criteria. Baseline characteristics between the two treatment groups (ANNAB and ANLIB) were comparable (Table 1). The median PFS was significantly longer in the ANNAB group compared to the ANLIB group (6.0 months vs. 4.7 months, log-rank test p = 0.0004; Fig. 1). Similarly, the median OS was significantly longer in the ANNAB group compared with the ANLIB group (10.0 months vs 7.3 months, log-rank test p < 0.0001; Fig. 2).

Eighteen patients in the ANNAB group completed the six cycles of the regimen. As of the last follow-up date of January 31, 2023, eight patients in the ANNAB group and two patients in the ANLIB group were still receiving anlotinib monotherapy. Among the patients in the ANNAB group, nine achieved PR and ten achieved SD, resulting in a significantly higher ORR compared to the ANLIB group (37.5% vs. 8.3%, p=0.02). A comparable DCR was observed between the two groups (79.2% vs. 62.5%, p=0.34). No CR was observed in either group (Fig. 3).

Safety

The incidence of AEs between the two groups was comparable, with the exception of peripheral neuropathy and neutropenia (Table 2). No grade 4 AEs were observed in either group, and the only grade 3 AE was neutropenia, which occurred in the ANNAB group. The incidence of AEs reported in this study was consistent with findings from previous studies investigating similar treatments and other treatment indications for these medications. Four patients in the ANNAB group and three patients in the ANLIB group required anlotinib dose reduction due to fatigue. No patients required a second dose adjustment. Overall, the combination regimen did not increase the severity of adverse events.

Our retrospective study suggests that the ANNAB regimen may be a promising therapeutic approach for patients with relapsed SCLC who have failed second-line therapy. Compared to anlotinib alone, treatment with ANNAB resulted in a significantly longer median PFS of 6.0 months and a median OS of 10.0 months at the cutoff date. These findings are particularly encouraging considering the poor prognosis of patients with relapsed SCLC, especially those with primary platinum-resistant disease (70.8% of our study population). In a real-world analysis of patients receiving various third-line regimens, the ORR was only 21.3%, and the median OS was 4.4 months^[14]. Notably, this is the first retrospective study to evaluate the efficacy and safety of the combination therapy of nab-paclitaxel and anlotinib for the treatment of relapsed SCLC in the third-line setting.

The ANNAB regimen was demonstrated to be well-tolerated in this study. Only one patient experienced grade 3 hematologic toxicity. The incidence of non-hematologic AEs observed was consistent with findings from previous studies investigating similar treatments and other treatment indications for these medications. Overall, the combination regimen did not appear to increase the severity of adverse events.

For patients with relapsed SCLC who have undergone two prior treatment regimens, the National Comprehensive Cancer Network (NCCN) guidelines offer limited standard treatment recommendations. Pembrolizumab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, has shown an ORR of 19.3% in SCLC patients who have received two or more prior chemotherapy regimens ^[15]. However, it should be borne in mind that this study involved a small sample size, and pembrolizumab was not approved for first-line extensive-stage SCLC (ED-SCLC) due to negative results in the KEYNOTE-604 trial^[16]. Nivolumab, another PD-1 monoclonal antibody, has been FDA-approved as a third-line treatment option, demonstrating an ORR of 11.9%^[17]. Unfortunately, nivolumab also failed to demonstrate efficacy in first-line and second-line treatment settings for SCLC, leading its manufacturer to withdraw these treatment indications ^{[18, 19]}.

In China, anlotinib has been established as a standard recommended treatment option for the third-line treatment of SCLC. A phase 2 study demonstrated that anlotinib resulted in a prolonged PFS of 3.4 months and OS of 2.4 months compared to placebo, with a manageable AE profile. However, the ORR observed with anlotinib monotherapy was only 4.9%. This limited efficacy, particularly for patients with a PS of 0–1, highlights the need for exploring more effective treatment strategies.

Compared to conventional paclitaxel, nab-paclitaxel has been shown in preclinical studies to effectively reach the tumor microenvironment, likely due to its unique pharmacokinetic profile. Clinical trials have demonstrated the antitumor activity of nab-paclitaxel in various solid tumors, including advanced NSCLC[20]. However, data for SCLC is limited, with most studies focusing on second-line therapy. A single-phase 2 study from Italy investigated nab-paclitaxel (100mg/m2 on days 1, 8, and 15 every 4 weeks) as a second-line therapy for SCLC. The study reported an ORR of 8% in the refractory group and 14% in the sensitive group^[21]. While the primary endpoint of ORR was not met, nab-paclitaxel demonstrated modest antitumor activity with a tolerable safety profile. A retrospective study from Japan evaluated nab-paclitaxel (75-100mg/m² on days 1, 8, and 15 every 4 weeks) as a second-line therapy and reported an ORR of 29.4% with manageable adverse events^[10]. Overall, these findings suggest that nab-paclitaxel may have some efficacy for relapsed SCLC, particularly in the second-line setting.

Limited data exists regarding the use of nab-paclitaxel as a third-line therapy for SCLC. Wang et al. reported an ORR of 24.3% with nab-paclitaxel administered at a dose of 130mg/m² on days 1 and 8 of a 21-day cycle in this setting. However, the median PFS was only 5.0 months, and the median OS was 9.0 months in their study ^[22]. Similarly, Kim et al. observed a 33% ORR with nab-paclitaxel monotherapy as a third-line treatment for relapsed or refractory SCLC, but this study included a small sample size of only nine patients who received 100mg/m² of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle^[23]. In conclusion, while nab-paclitaxel monotherapy appears to demonstrate modest efficacy and tolerability in the third-line treatment of SCLC, further investigation is warranted due to the limited data available, particularly from larger, well-designed clinical trials.

Unlike most studies investigating nab-paclitaxel in lung cancer, our study employed a higher dose of 260mg/m² administered every 3 weeks, which aligns more closely with dosing regimens used in breast cancer. This approach reflects the absence of standardized guidelines for the dosing and schedule of nab-paclitaxel specifically for SCLC. Notably, despite the difference in our dosing regimen compared to other studies, the observed toxicity profile of nab-paclitaxel was consistent with previous reports.

Our study has some limitations that should be acknowledged. First, its retrospective design and single-center nature limit the generalizability of the findings. Second, the lack of standardized dosing and schedule for nab-paclitaxel in SCLC, as evidenced by the variations observed across different studies, necessitates further investigation through randomized controlled trials to establish optimal treatment regimens. Additionally, the study population was exclusively Chinese, highlighting the need for multicenter trials with broader patient demographics. Finally, a randomized prospective study is warranted to definitively address the questions raised by our findings.

Our study provides hitherto undocumented evidence of the efficacy and safety of the ANNAB regimen as a third-line treatment for patients with relapsed SCLC. Compared to current treatment options for this patient population, the ANNAB regimen demonstrated a promising efficacy profile, with a median PFS of 6.0 months and a median OS of 10.0 months. Additionally, the regimen was well-tolerated, with a manageable safety profile. These findings warrant further investigation through larger, prospective clinical trials to confirm the efficacy and safety of the ANNAB regimen for patients with relapsed SCLC.

Acknowledgements

We thank all participants and patients who participated in this study.

Competing Interests

The author reports no conflicts of interest in this work.

Funding

This work was supported by the research fund of the Beijing Science and Technology Innovation Medical Development Foundation (KC2021-JX-0186-20) and ShanDong Provincial Medical Association (No. YXH2022ZX02028). The funding body played no role in the design, data collection, analysis, interpretation of data in this manuscript.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author, Professor Qi-Sen Guo, upon reasonable request.

Authors' contributions

Li-Jun Tian wrote the manuscript; Fei-fei Zhou performed the experiment; Min-Dai performed the data analyses; Jun-Li Liu contributed significantly to analysis; Fan-Chan Meng performed data collection; Wen-Chao Xu helped data collection; Qi-Sen Guo contributed to the conception of the study.

Ethics approval and consent to participate

The study was approved by the Human Ethics Committee of Binzhou Medical University Hospital.

Patient consent for publication

All patients were eligible to participate in this study upon providing written informed consent.

Sung H, Ferlay J, Siegel R L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021,71(3):209-249. DOI: 10.3322/caac.21660.
Dingemans A C, Fruh M, Ardizzoni A, et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up()[J]. Ann Oncol, 2021,32(7):839-853. DOI: 10.1016/j.annonc.2021.03.207.
Horn L, Mansfield A S, Szczesna A, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer[J]. N Engl J Med, 2018,379(23):2220-2229. DOI: 10.1056/NEJMoa1809064.
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[J]. Lancet, 2019,394(10212):1929-1939. DOI: 10.1016/S0140-6736(19)32222-6.
Ganti A, Loo B W, Bassetti M, et al. Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw, 2021,19(12):1441-1464. DOI: 10.6004/jnccn.2021.0058.
von Pawel J, Jotte R, Spigel D R, et al. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer[J]. J Clin Oncol, 2014,32(35):4012-4019. DOI: 10.1200/JCO.2013.54.5392.
Cheng Y, Wang Q, Li K, et al. Anlotinib vs placebo as third- or further-line treatment for patients with small cell lung cancer: a randomised, double-blind, placebo-controlled Phase 2 study[J]. Br J Cancer, 2021,125(3):366-371. DOI: 10.1038/s41416-021-01356-3.
Naito Y, Tamiya A, Tamiya M, et al. Efficacy of nanoparticle albumin-bound paclitaxel regimens for relapsed small cell lung cancer: A retrospective analysis[J]. Medicine (Baltimore), 2017,96(35):e7884. DOI: 10.1097/MD.0000000000007884.
Sugiyama K, Kogure Y, Torii A, et al. Solvent-based paclitaxel or nab-paclitaxel for heavily treated relapsed/refractory small cell lung cancer: Retrospective single-institution observational study[J]. Medicine (Baltimore), 2019,98(9):e14758. DOI: 10.1097/MD.0000000000014758.
Nakao M, Fujita K, Suzuki Y, et al. Nab-paclitaxel Monotherapy for Relapsed Small Cell Lung Cancer: Retrospective Analysis and Review[J]. Anticancer Res, 2020,40(3):1579-1585. DOI: 10.21873/anticanres.14105.
de Kock I, Mirhosseini M, Lau F, et al. Conversion of Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group Performance Status (ECOG) to Palliative Performance Scale (PPS), and the interchangeability of PPS and KPS in prognostic tools[J]. J Palliat Care, 2013,29(3):163-169.
Eisenhauer E A, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)[J]. Eur J Cancer, 2009,45(2):228-247. DOI: 10.1016/j.ejca.2008.10.026.
Smith T J, Bohlke K, Lyman G H, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update[J]. J Clin Oncol, 2015,33(28):3199-3212. DOI: 10.1200/JCO.2015.62.3488.
Coutinho A D, Shah M, Lunacsek O E, et al. Real-world treatment patterns and outcomes of patients with small cell lung cancer progressing after 2 lines of therapy[J]. Lung Cancer, 2019,127:53-58. DOI: 10.1016/j.lungcan.2018.11.009.
Piha-Paul S A, Oh D Y, Ueno M, et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies[J]. Int J Cancer, 2020,147(8):2190-2198. DOI: 10.1002/ijc.33013.
Rudin C M, Awad M M, Navarro A, et al. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study[J]. J Clin Oncol, 2020,38(21):2369-2379. DOI: 10.1200/JCO.20.00793.
Ready N, Farago A F, de Braud F, et al. Third-Line Nivolumab Monotherapy in Recurrent SCLC: CheckMate 032[J]. J Thorac Oncol, 2019,14(2):237-244. DOI: 10.1016/j.jtho.2018.10.003.
Arriola E, Gonzalez-Cao M, Domine M, et al. Addition of Immune Checkpoint Inhibitors to Chemotherapy vs Chemotherapy Alone as First-Line Treatment in Extensive-Stage Small-Cell Lung Carcinoma: A Systematic Review and Meta-Analysis[J]. Oncol Ther, 2022,10(1):167-184. DOI: 10.1007/s40487-021-00182-0.
Spigel D R, Vicente D, Ciuleanu T E, et al. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331(☆)[J]. Ann Oncol, 2021,32(5):631-641. DOI: 10.1016/j.annonc.2021.01.071.
Yardley D A. nab-Paclitaxel mechanisms of action and delivery[J]. J Control Release, 2013,170(3):365-372. DOI: 10.1016/j.jconrel.2013.05.041.
Gelsomino F, Tiseo M, Barbieri F, et al. Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)[J]. Br J Cancer, 2020,123(1):26-32. DOI: 10.1038/s41416-020-0845-3.
Wang Y, Li L, Xu C. Nanoparticle Albumin Bound Paclitaxel in the Third-Line Treatment of Recurrent Small Cell Lung Cancer in Real-World Practice: A Single Center Experience[J]. Technol Cancer Res Treat, 2021,20:2091174633. DOI: 10.1177/15330338211050775.
Yoshida H, Kim Y H, Ozasa H, et al. Albumin-bound paclitaxel for the treatment of refractory or relapsed small-cell lung cancer[J]. Mol Clin Oncol, 2016,5(1):213-215. DOI: 10.3892/mco.2016.887.

Table 1. Baseline characteristics of patients

ANNAB (n=24), no. (%)

Anlotinib (n=24), no. (%)

P value

Age (years)

Median (range)

59.5 (46-75)

62.5 (45-75)

0.7318

Sex

Male

Female

20 (83.3)

4 (16.7)

19 (79.2)

5 (20.8)

1.0000

ECOG performance status

0.7601

Smoking history

Never

Current

Former

0.8145

Disease stage

Limited

Extensive

0.7238

Brain metastasis

Yes

1.0000

Previous PCI

Yes

1.0000

Previous radiotherapy

Yes

0.7590

Brain radiotherapy

Yes

0.4614

Pattern of relapse from chemotherapy

Sensitive

Refractory/resistant

0.5469

Table 2. Safety summary.
	ANNAB (n=24), no. (%)	ANLIB (n=24), no. (%)	P
Fatigue	16 (66.7%)	13 (54.2%)	0.5556
Anemia	9 (37.5)	4 (16.7%)	0.1930
Peripheral neuropathy	5 (20.8%)	0 (0%)	0.0496
Hypertension	14 (58.3%)	16 (66.7%)	0.7661
Neutropenia	7 (29.2%)	1 (4.2%)	0.0479
Leukopenia	6 (25.0%)	2 (8.3%)	0.2448
Vomiting	2 (8.3%)	0	0.4894
Nausea	4 (16.7%)	1 (4.2%)	0.3475
Trombocytopenia	3 (12.5%)	1 (4.2%)	0.6085
Hand and foot skin reaction	16 (66.7%)	10 (41.7%)	0.1468
Mucositis oral	7(29.2%)	5 (20.8%)	0.7400
Liver toxicity	3 (12.5%)	1 (4.2%)	0.6085

No competing interests reported.

Download PDF

Reviews received at journal
12 Aug, 2024
Reviewers agreed at journal
12 Aug, 2024
Reviewers invited by journal
12 Aug, 2024
Editor assigned by journal
12 Aug, 2024
Editor invited by journal
15 Jul, 2024
Submission checks completed at journal
12 Jul, 2024
First submitted to journal
11 Jul, 2024

You are reading this latest preprint version

The efficacy and safety of nab-paclitaxel plus anlotinib in small-cell Lung Cancer for third- line therapy

Status:

Version 1

Abstract

Figures

Introduction

Methods

Patients

Treatment schedule

Evaluations

Outcomes

Statistical analysis

Results

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

Version 1