Second-line treatment in patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma: a systematic review and meta-analysis

Mairead Mcnamara, Melissa Frizziero, Timothy Jacobs, Angela Lamarca, Richard Hubner, Juan Valle, Amir Eitan

Research output: Contribution to journalArticlepeer-review

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-67>55% had lower RR (β=-0.73) and shorter OS (β=-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.

Original languageEnglish
JournalTherapeutic Advances in Medical Oncology
Publication statusAccepted/In press - 4 Mar 2020

Keywords

  • Second-line treatment
  • advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma
  • meta-analysis
  • systematic review
  • survival

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