Prostate-sing membrane antigen (PSMA)-focused radionuclide therapy decreased the threat of illness progression or loss of life versus cabazitaxel (Jevtana) in men with beforehand treated metastatic castration-resistant prostate cancer (CRPC), and with fewer toxicities and better quality of life, a randomized phase II trial confirmed.
Within the so-called TheraP seek recordsdata from, which concerned 200 sufferers with excessive PSMA expression and revolutionary illness following docetaxel, lutetium-177 PSMA-617 improved radiographic progression-free survival (PFS) over cabazitaxel (HR 0.63, 95% CI 0.46-0.86, P=0.0028), reported Michael Hofman, MBBS, of the Peter MacCallum Most cancers Centre in Melbourne, Australia.
While median radiographic PFS used to be same, at 5.1 months in every arm, 12-month rates had been 19% with the PSMA-focused radionuclide therapy versus 3% with cabazitaxel, in line with findings offered at the digital Genitourinary Cancers Symposium and printed simultaneously in The Lancet. Overall survival (OS) recordsdata had been no longer used.
“Lutetium PSMA-617 represents a brand current class of efficient therapy for men with castration-resistant prostate cancer,” said Hofman.
Lutetium-177 PSMA-617 is a exiguous molecule that delivers excessive ranges of beta-particle radiation to PSMA-expressing cells, Hofman defined, nevertheless low doses to traditional tissue.
“A power of the seek recordsdata from is an brisk control arm utilizing cabazitaxel — a validated life-prolonging therapy bolstered with the publication of the CARD trial,” he said.
Writing in an accompanying editorial, Thomas Hope, MD, of the University of California San Francisco, and Jeremie Calais, MD, of the University of California Los Angeles, agreed.
“Cabazitaxel is an efficient therapy for sufferers who own already bought docetaxel,” they neatly-known, while including that assorted PSMA-focused radiopharmaceutical therapy trials are utilizing weaker comparator hands, that might per chance also just restrict their interpretation.
Hope and Calais called attention to the PFS curves in TheraP, which simplest separated at 6 months, by which point the PSMA-focused agent overtook cabazitaxel.
“This finding shall be the most bright factor of this seek recordsdata from and highlights two aspects. First, PSMA-focused radiopharmaceutical therapy medicines is cumulative, unlike chemotherapy. Tumor cells receive doses of radioactivity every 6 weeks, and therefore the medicine attain received’t be proven today,” they wrote. “Second, a subpopulation of sufferers exist who own a protracted own the profit of PSMA-focused radiopharmaceutical therapy, pushing out the tail of the PSMA-focused radiopharmaceutical therapy progression-free survival curves.”
As used to be beforehand reported, TheraP met its foremost endpoint, with lutetium-177 PSMA-617 resulting in a elevated percentage of fellows seeing a 50% or better reduction in prostate-sing antigen (PSA) ranges from baseline in comparison with cabazitaxel (66% vs 37%; P<0.0001).
Objective response rates in the current study were doubled with the radiopharmaceutical therapy, at 49% compared with 24% with cabazitaxel. Men in the lutetium-177 PSMA-617 arm also had less pain following treatment, with 60% reporting improvements compared with 43% of those in the cabazitaxel arm (relative risk 1.4, 95% CI 0.9-2.2, P=0.10).
“Lutetium PSMA-617 was significantly more active than cabazitaxel with fewer grade 3/4 adverse events, and patient-reported outcomes in multiple domains favored lutetium PSMA,” said Hofman.
Grade 3/4 toxicities occurred in 33% of patients treated with lutetium-177 PSMA-617 versus 53% with cabazitaxel, with the most common being neutropenia (4% vs 13%, respectively), thrombocytopenia (11% vs 0%), anemia (8% each), diarrhea (1% vs 5%), and fatigue (5% vs 4%).
On the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30), significant improvements with lutetium-177 PSMA-617 were seen in social functioning, fatigue, insomnia, and diarrhea, and all other measures trended in favor of the radionuclide group. There was also lower incidence of skin rash, sore hands/feet, altered taste, dizziness, urinary symptoms, and diarrhea with lutetium-177 PSMA-617.
The study also demonstrated improved deterioration-free survival (DFS) with lutetium-177 PSMA-617, which was defined as time to a ≥10 point deterioration in EORTC QLQ-C30 global health status, disease progression, death, or treatment discontinuation. At 6 months, DFS rates were 29% in the study arm versus 13% in the cabazitaxel arm. At 12 months, these rates were 21% versus 1%, respectively.
TheraP was an open-label, investigator-initiated phase II trial that from 2018 to 2019 randomized 200 men with metastatic CRPC who had previously been treated with docetaxel 1:1 to either lutetium-177 PSMA-617 (delivered intravenously every 6 weeks for up to six cycles, starting at 8.5 GBq and decreasing 0.5 GBq each cycle) or cabazitaxel (20 mg/m2 via IV for up to 10 cycles).
A paired diagnostic test involving PET-CT imaging with gallium-68Ga-PSMA-11 was used to exclude men who might not benefit from the treatment. Patients needed to have a PSMA SUVmax >20 at any achieve for inclusion, as neatly as no FDG-sure or PSMA-negative sites of illness. After screening 291 sufferers, 91 had been excluded attributable to low PSMA expression (n=29), FDG-discordant illness (n=51), or assorted causes (n=11). Fifteen sufferers dropped out within the cabazitaxel arm versus none within the seek recordsdata from arm, a limitation of the seek recordsdata from, Hofman neatly-known.
Sufferers had a median age of 72 years, 91% had beforehand bought androgen receptor-directed therapy (abiraterone [Zytiga], enzalutamide [Xtandi], or every), and about 95% of sufferers had an ECOG efficiency keep score of 0 or 1.
PSA PFS confirmed a same hazard ratio to the radiographic PFS analysis, as did per-protocol sensitivity analyses.
Ian Ingram joined MedPage This day in 2018 as Deputy Managing Editor, and covers oncology for the positioning.
The seek recordsdata from used to be funded by the Prostate Most cancers Foundation of Australia, Australian Nuclear Science and Technology Organisation, the Mighty Gentleman Run, Or no longer it is a Bloke Thing, and CAN4CANCER. Novartis supplied PSMA-617.
Hofman disclosed relationships with Endocyte, Janssen, Genzyme, and Ipsen. Co-authors reported assorted ties to industry.