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Comparative Outcomes of Second-line Topoisomerase-I Inhibitor Therapies on Neuroendocrine Carcinoma

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Abstract

Introduction

This investigation aims to assess the outcomes for second-line therapies to treat extrapulmonary neuroendocrine carcinoma (EP-NEC) after first-line platinum-based chemotherapy.

Methods

With IRB approval, we conducted a retrospective study of EP-NEC patients that progressed on first-line platinum chemotherapy from 2008 to 2018. Demographic data and treatment-related characteristics were collected and represented as descriptive statistics. The primary endpoints include overall survival (OS) and progression-free survival (PFS). OS and PFS were estimated and stratified by site of primary (gastroenteropancreatic [GEP] versus non-GEP) and type of second-line therapy (irino/topotecan versus others). Log-rank test and Kaplan–Meier curves were used to compare survival distributions between groups.

Results

Forty-seven patients met eligibility, with median age 65 (range 31–82), 62% male, and 83% White; 22 were GEP and 25 were non-GEP primary. Thirty patients (63.8%) received second-line therapy where 11 received irinotecan/topotecan (ir/to), while 19 received other agents (temozolomide, other platinum agents, gemcitabine, paclitaxel, pembrolizumab, and sunitinib). The median OS was 10.3 months in the ir/to group versus 13.4 months for other therapies, p = 0.10. The median PFS for ir/to therapy compared to other therapies was 2.0 months versus 1.8 months, respectively, p = 0.72. The OS and PFS with and without ir/to were not significantly different by the primary site (p = 0.61 and p = 0.21).

Discussion/Conclusion

Many EP-NEC patients undergo second-line therapies. Interestingly, outcomes for ir/to-containing second-line therapies were not statistically different from other agents, regardless of the site of primary. With approval of new second-line therapies for small cell lung cancer, further research in therapeutic options is needed for this aggressive disease.

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Funding

This research is supported by the Cancer Center Support Grant (CCSG) P30 CA006927 and philanthropic funds.

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Authors and Affiliations

  1. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA

    Ho-Man Yeung, Krishnalatha Sreekrishnanilayam & Namrata Vijayvergia

  2. Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA

    Caitlin Meeker

  3. Bioinformatics and Biostatistics Facility, Fox Chase Cancer Center, Philadelphia, PA, USA

    Mengying Deng

  4. Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

    Ho-Man Yeung, Sonali Agrawal & Haaris Abdullah

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  1. Ho-Man Yeung
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  2. Krishnalatha Sreekrishnanilayam
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Contributions

Ho-Man Yeung: conception and design, acquisition, analysis and interpretation of data, drafting and revising of manuscript, approval of final version of manuscript. Krishnalatha Sreekrishnanilayam: acquisition of data, drafting and revising of manuscript, approval of final version of manuscript. Caitlin Meeker: acquisition of data, drafting and revising of manuscript, approval of final version of manuscript. Mengying Deng: analysis of data, drafting and revising of manuscript, approval of final version of manuscript. Sonali Agrawal: acquisition of data, drafting and revising of manuscript, approval of final version of manuscript. Haaris Abdullah: acquisition of data, drafting and revising of manuscript, approval of final version of manuscript. Namrata Vijayvergia: conception and design, analysis and interpretation of data, drafting and revising of manuscript, approval of final version of manuscript.

Corresponding author

Correspondence to Ho-Man Yeung.

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Ethics Approval

This research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The study protocol was reviewed and approved by the Fox Chase Cancer Center Institutional Review Board, protocol ID #18–8007. Informed consent and HIPAA authorization were waived.

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The authors declare no competing interests.

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Yeung, HM., Sreekrishnanilayam, K., Meeker, C. et al. Comparative Outcomes of Second-line Topoisomerase-I Inhibitor Therapies on Neuroendocrine Carcinoma. J Gastrointest Canc 54, 73–79 (2023). https://doi.org/10.1007/s12029-021-00800-0

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