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Second-line treatment in patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma: a systematic review and meta-analysis
McNamara, Mairead G Frizziero, Melissa Jacobs, Timothy Lamarca, Angela Amir, E.
McNamara, Mairead G
Frizziero, Melissa
Jacobs, Timothy
Lamarca, Angela
Amir, E.
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Abstract
Background: There is no standard second-line treatment for patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma (EP-PD-NEC). This study explored data evaluating second-line treatment in these patients. Methods: A search of MEDLINE and EMBASE identified studies reporting survival and/or response data for patients with EP-PD-NEC receiving second-line therapy. Association between various factors (age, gender, ECOG performance status, primary tumour location, morphology, Ki-67, treatment and grade 3/4 haematological toxicity) and response rate (RR), progression-free (PFS) and overall survival (OS) were assessed with a mixed effects meta-regression weighted by individual study sample size. Due to a small sample size, associations were reported quantitatively, based on magnitude of beta coefficient rather than statistical significance. Results: Of 83 identified studies, 19 were eligible, including 4 prospective and 15 retrospective studies. Analysis comprised 582 patients, with a median number of 19 patients in each study (range 5-100). Median age was 59 years (range 53-66). Median RR was 18% (range 0-50; 0% for single-agent everolimus, temozolomide, topotecan; 50% with amrubicin), median PFS was 2.5 months (range 1.15-6.0) and median OS was 7.64 months (range 3.2-22.0). Studies with a higher proportion of patients with a Ki-6755% had lower RR (beta = -0.73) and shorter OS (beta = -0.82). Conclusion: Second-line therapy for patients with advanced EP-PD-NEC has limited efficacy and the variety of regimens used is diverse. Ki-67"55% is associated with worse outcomes. Prospective randomised studies are warranted to enable exploration of new treatment strategies."
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Date
2020
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M. G. McNamara, M. Frizziero, T. Jacobs et al. Second-line treatment in patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma: a systematic review and meta-analysis. Ther Adv Med Oncol. 2020;12:1758835920915299.