[177Lu]Lu-PSMA-617 vs Cabazitaxel in Patients With Metastatic Castration-Resistant Prostate Cancer
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
Lutetium-177 [177Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer. We aimed to compare [177Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer.
METHODS
We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 [68Ga]Ga-PSMA-11 and 2-flourine-18[18F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to [177Lu]Lu-PSMA-617 (6·0–8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428.
FINDINGS
Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to [177Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [177Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16–42; p<0·0001; and 66% vs 44% by treatment received; difference 23% [9–37]; p=0·0016). Grade 3–4 adverse events occurred in 32 (33%) of 98 men in the [177Lu]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to [177Lu]Lu-PSMA-617.
INTERPRETATION
[177Lu]Lu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. [177Lu]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel.
FUNDING
Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, The Distinguished Gentleman's Ride, It's a Bloke Thing, and CAN4CANCER.
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Additional Info
Disclosure statements are available on the authors' profiles:
[177Lu]Lu-PSMA-617 Versus Cabazitaxel in Patients With Metastatic Castration-Resistant Prostate Cancer (TheraP): A Randomised, Open-Label, Phase 2 Trial
Lancet 2021 Feb 27;397(10276)797-804, MS Hofman, L Emmett, S Sandhu, A Iravani, AM Joshua, JC Goh, DA Pattison, TH Tan, ID Kirkwood, S Ng, RJ Francis, C Gedye, NK Rutherford, A Weickhardt, AM Scott, ST Lee, EM Kwan, AA Azad, S Ramdave, AD Redfern, W Macdonald, A Guminski, E Hsiao, W Chua, P Lin, AY Zhang, MM McJannett, MR Stockler, JA Violet, SG Williams, AJ Martin, ID Davis, TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials GroupFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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This is an important trial; congratulations are due to the authors for executing an important prospective randomized study. This is good work.
The study by Michael Hofman and colleagues in Australia compared cabazitaxel with PSMA-617 lutetium-177 and enrolled patients who were considered to be PSMA-positive and, importantly, excluded patients who had FDG PET–discordant lesions. A total of 291 people were screened for the trial and 91 patients were excluded either because predominantly they had either PSMA uptake that was insufficient for randomization or because they had FDG-discordant disease.
The patients included in the trial had to have failed a previous abiraterone- or enzalutamide-type novel hormonal agent, and progressive disease at the time of trial entry was required.
What was found was interesting in that, by a variety of endpoints including time to PSA progression and PSA response rate, as well as radiographic progression and time to image-based progression, those patients treated with the PSMA lutetium-177 had better outcomes. Notably missing, however, was adequate survival information, making this trial quite provocative but not definitive, and it will not lead to regulatory approval as it was a randomized phase II trial.
The VISION trial with PSMA lutetium-177 in a similar setting of post abiraterone/ post docetaxel has now completed accrual, and the investigators anticipate having results later in 2021. This is a definitive phase III trial and could lead to regulatory approval should the results be positive.