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Outcomes of Second-Line Therapies in Patients With Metastatic de Novo and Treatment-Emergent Neuroendocrine Prostate Cancer: A Multi-Institutional Study - Beyond the Abstract

Small cell or neuroendocrine prostate cancer (NEPC) is a rare and aggressive disease characterized by a low serum prostate-specific antigen (PSA) and visceral metastatic disease at diagnosis. NEPC can present as de novo metastatic disease (<1% of prostate cancers) or as treatment-emergent NEPC (T-NEPC), which arises from pre-existing metastatic castrate-resistant prostate cancer (mCRPC) (estimated to occur in 17-30% of mCRPC cases). On a histologic level, NEPC is morphologically similar to the oat cell or intermediate cell appearance of small cell lung cancer (SCLC) with nearly 90% of cases staining positive for a neuroendocrine marker.

Clinical data for the treatment of metastatic NEPC remains sparse. Platinum-based chemotherapy is a recommended first-line treatment based on small phase II studies and data extrapolated from SCLC. However, in the second-line setting, there are limited clinical data and guidelines available for oncologists treating patients with NEPC. To address this clinical need, this retrospective study gathered real-world data on clinical practice patterns among oncologists and evaluated the treatment and outcomes of patients after second-line therapy for de novo NEPC and T-NEPC.

Patients with a pathologic diagnosis of metastatic de novo NEPC or T-NEPC between 2000-2020 who received first-line platinum-based chemotherapy and any second-line systemic therapy were included. Patients were selected via the electronic medical record at 8 North American cancer centers. A total of 58 patients (32 with de novo NEPC and 26 with T-NEPC) were included. Patients had a median age of 65.0 years (IQR 59.2-70.3) and a median PSA of 3.0 ng/dL (IQR 0.6-17.9) at diagnosis. After first-line platinum chemotherapy, second-line treatment regimens were highly varied. Out of the 58 patients, 21 patients (36.2%) received platinum chemotherapy, 10 (17.2%) received taxane monotherapy, 11 (19.0%) received immunotherapy, 10 (17.2%) received other chemotherapy, and 6 (16.2%) received other systemic therapy. Among 41 evaluable patients, the objective response rate across all second-line therapies was 23.5%. However, patients re-treated with platinum-based chemotherapy were more likely to have an objective response (9 patients, 50.0%, p=0.016). The mOS after the start of second-line therapy was 7.4 months (95% CI 6.1-11.9). There was no clear benefit in mOS for one option over another, although mOS was the shortest for patients treated with immunotherapy at 2.4 months (95% CI 1.8-NR).

In this multi-institutional, retrospective study, second-line systemic therapies after first-line platinum-based chemotherapy were highly varied yet limited in their treatment of NEPC. Further clinical trials addressing second-line therapies in NEPC are needed to aid clinical decision making and improve the prognosis of this lethal disease. Clinical trials in NEPC are ongoing for immune checkpoint inhibitors, antibody-drug conjugates, novel enzymatic pathway inhibitors, and conventional chemotherapy. This study demonstrates the importance of considering clinical trial enrollment for patients with metastatic NEPC as the current treatment landscape remains wide-ranging while offering limited clinical benefit to patients.

Kaplan-Meier survival curves of overall cohort stratified by second-line therapy.
Kaplan_Meier_NEPC.png

Written by: Corbin J Eule,1 Junxiao Hu,2 Sulaiman Al-Saad,3 Katharine Collier,4 Patrick Boland,5 Akeem R Lewis,6 Rana R McKay,7 Vivek Narayan,8 Dominick Bosse,3 Amir Mortazavi,4 Tracy L Rose,5 Brian A Costello,6 Alan H Bryce,9 Elaine T Lam10

  1. Division of Medical Oncology, University of Colorado Cancer Center, Aurora, CO.
  2. Biostatistics and Bioinformatics, University of Colorado Cancer Center Biostatistics Core, Aurora, CO.
  3. Division of Medical Oncology, The Ottawa Hospital Cancer Center, Ottawa, Ontario, Canada.
  4. Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, and the Comprehensive Cancer Center, Columbus, OH.
  5. Division of Medical Oncology, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC.
  6. Division of Medical Oncology, Mayo Clinic Cancer Center, Rochester, MN.
  7. Division of Medical Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA.
  8. Division of Medical Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
  9. Division of Medical Oncology, Mayo Clinic, Phoenix, AZ.
  10. Division of Medical Oncology, University of Colorado Cancer Center, Aurora, CO. 

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