The Use of Lurbinectedin for the Treatment of Small Cell and Neuroendocrine Carcinoma of the Prostate

Abstract

Introduction: Lurbinectedin is FDA approved for treatment of metastatic small cell lung cancer (SCLC) following progression on or after platinum-based chemotherapy. Prostatic small cell or neuroendocrine carcinoma (SC/NEPC) behaves like SCLC; however, no safety or efficacy data for lurbinectedin in SC/NEPC exists.

Patients and methods: All SC/NEPC patients treated with lurbinectedin across 4 academic oncology centers were identified. Baseline patient data and lurbinectedin outcomes including radiographic responses (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]), progression free survival (PFS), overall survival (OS), and treatment-related adverse events (trAEs) were described. Clinical benefit rate (CBR) included CR, PR, or SD on imaging. Descriptive statistics were performed.

Results: At first lurbinectedin dose, all 18 patients had metastatic disease. Median age was 63.5 (Range: 53-84), number of prior systemic therapies was 4 (Range: 2-7), and lurbinectedin cycles completed was 5 (Range: 1-10). ADT was administered during lurbinectedin treatment in 9/18 patients. CBR was 9/16 (56%). The most common trAEs were fatigue and anemia. Median OS and PFS were 6.01 (0.23-16.69) and 3.35 (0.16-7.79) months.

Conclusions: Lurbinectedin showed modest but significant clinical benefit in some patients with SC/NEPC and demonstrated an acceptable toxicity profile with no hospitalizations from trAEs. SC/NEPC is an aggressive disease with a poor prognosis for which more treatment options are needed. Evidence for subsequent treatments after platinum-based chemotherapy is lacking. Lurbinectedin is an active treatment option for SC/NEPC; however, larger confirmatory studies are needed.

Keywords: Anaplastic prostate cancer; Metastatic prostate cancer; Neuroendocrine prostate cancer; Small cell prostate cancer; Transcription inhibitor.

Figure 1. Depicts the individual treatments received prior to and including lurbinectedin.

The vertical red dashed line represents the time of SC/NEPC diagnosis. The treatments to the left of the red dashed line indicate treatment prior to SC/NEPC diagnosis. The treatments to the right of the red line indicate treatments administered after SC/NEPC diagnosis. The underlined patients are those who received treatment prior to −40 months. Treatments administered to patient 3 prior to −40 months included GnRH receptor antagonist (−82 to −79 mo.), GnRH receptor agonist (−82.1 to 31.1 month), abiraterone + prednisone (−45.4 to 0.43 month), and nonsteroidal antiandrogen (−56.4 to −46.2 month). Patient 7 was administered nonsteroidal antiandrogen (−46.9 to 46.8 month). Patient 9 was administered GnRH receptor antagonist (−76.3 to −76.2 month) and GnRH receptor agonist (−75.0 to −70.8).

Figure 2. Kaplan–Meier OS and PFS curves.

The median PFS on lurbinectedin was 3.35 month (0.16–7.79 month) (A). The median OS on lurbinectedin was 6.01 month (0.23–16.69 month) (B). On subgroup analysis (C), the median OS in the PR group was 8.44 mo. (5.75–8.48 month). The median OS in the SD group was 10.94 month (4.57–16.69 month). The median OS in the PD group was 4.14 mo. (1.08–6.01 month). The black dashed lines represent the median PFS or OS.