ASCO 2023: A Feasibility Study of 177Lu-PSMA Radioligand Therapy Alternated with Radium-223 in Patients with Bone-Metastatic, Oligo-Metastatic, Hormone-Sensitive Prostate Cancer After Curative Therapy: The DUET Study

( The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. André Vis presented the results of DUET, a feasibility study evaluating 177Lu-PSMA radioligand therapy alternated with radium-223 in patients with oligometastatic hormone sensitive prostate cancer with bone metastases following curative therapy.

LuPSMA-617 combines PSMA-617 and the beta-emitter lutetium to deliver targeted ß-particle radiation to PSMA-expressing cells and the surrounding microenvironment. LuPSMA-617 has been demonstrated to improve overall survival (OS) outcomes, compared to standard of care, in men with PSMA-positive mCRPC who had previously received treatment with a next-generation androgen receptor signaling inhibitor and one or two prior lines of taxane chemotherapy (median OS: 15.3 vs 11.3 months; HR: 0.62 [95% CI: 0.52 – 0.74]; p < 0.001, one-sided).1

Radium-223 dichloride (radium-223) is a targeted alpha emitter that selectively binds to areas of increased bone turnover in bone metastases and emits high-energy alpha particles of short range (<100 μm), resulting in double-stranded DNA breaks. This results in a potent and highly localized cytotoxic effect in the target areas. Radium-223 was FDA approved in 2013 based on the results of the ALSYMPCA, a phase 3, randomized, double-blind, placebo-controlled trial that randomized 921 patients in a 2:1 fashion to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo. Patients receiving radium-223 had a significantly improved median overall survival (OS) of 14 versus 11.2 months (HR: 0.70, 95% CI: 0.55 – 0.88).2

However, neither agent (alone nor in combination) has demonstrated significantly improved oncologic outcomes in the metastatic castrate-sensitive state. To date, the optimal therapy in patients with oligometastatic bone-involving, hormone sensitive prostate cancer post-definitive therapy has yet to be defined. 

DUET (NL81658.029.22) is an interventional, single arm, phase 1/2 trial at a single institution (Amsterdam University Medical Center) that will investigate if alternating treatment with two cytotoxic radioligand therapies (alpha emitter: Ra-223 and beta emitter: 177Lu-PSMA) is feasible and safe. This study will include 8 patients with low-volume, PSMA expressing, mHPSC with evidence of radiologic progression and 2-5 bone metastases and/or 0-3 nodal lesions. The PSA doubling time for eligible patients is <6 months.

Patients enrolled in the trial will receive three intravenous applications of Radium-223, at a dose of 5.5 kBq/kg body weight at weeks 0, 4, and 8 (±1), and two intravenous applications of 7.4 GBq 177Lu-PSMA at weeks 6 and 12 (±1).


The primary endpoint is the feasibility and safety of alternating Ra-223 and 177Lu-PSMA in oligometastatic, bone-involving mHSPC. Secondary endpoints will include:

  • Toxicity and (serious) adverse events monitored and reported in concordance with the NCI CTCAE v5.0
  • Assessment of the xerostomia inventory
  • PSA levels on follow-up at 3, 6 and 12-months

Presented by: André Vis, MD, PhD, Associate Professor, Amsterdam University Medical Center, Amsterdam, Netherlands

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023. 


  1. Sartor O, de Bono J, Chi KN et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103.
  2. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213-223.