Targeted radioligand therapy viable for certain men with advanced prostate cancer
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CHICAGO — Lutetium Lu 177 vipivotide tetraxetan is a viable option for certain men with advanced prostate cancer, according to study results presented at ASCO Annual Meeting.
Lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis) appeared associated with a higher response rate, greater PFS benefit and better patient-reported outcomes than cabazitaxel (Jevtana, Sanofi Genzyme) for men with metastatic castration-resistant, prostate-specific membrane antigen-positive prostate cancer whose disease progressed after docetaxel and an androgen receptor pathway inhibitor.
OS appeared comparable between the two therapies, results of the TheraP ANZUP 1603 trial showed.
Background and methods
Lutetium Lu 177 vipivotide tetraxetan — formerly called 177Lu-PSMA-617 — is the first targeted radioligand therapy for treatment of progressive, prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer. PSMA is highly expressed in more than 80% of men with prostate cancer.
The TheraP trial included 200 men with metastatic castration-resistant prostate cancer whose disease progressed after docetaxel.
Eligibility criteria included high PSMA expression — defined as at least one site with standard uptake valuemax of 20 or higher — and 18F-FDA demonstrating no discordant disease (ie, FDG-positive and PSMA-negative).
Researchers randomly assigned 99 men to lutetium Lu 177 vipivotide tetraxetan via IV every 6 weeks (8.5 GBq for cycle 1, decreasing by 0.5 GBq with each subsequent cycle, for a maximum six cycles).
The other 101 men received cabazitaxel dosed at 20 mg/m2 every 3 weeks for a maximum 10 cycles.
PSA response served as the primary endpoint. Secondary endpoints included OS, PFS, radiographic PFS, objective tumor response, pain response, health-related quality of life and adverse events.
Results
Previously reported results — based on median follow-up of 18.4 months — showed lutetium Lu 177 vipivotide tetraxetan improved PSA response rate (66% vs. 37%), RECIST response rate (49% vs. 24%) and PFS (HR = 0.63). The agent also appeared associated with a lower rate of grade 3/grade 4 toxicities (33% vs. 53%) and better patient-reported outcomes.
At ASCO, Michael S. Hofman, MBBS, FRACP — director of prostate cancer theranostics, as well as nuclear medicine and molecular imaging physician at Peter MacCallum Cancer Centre in Victoria, Australia — reported updated outcomes based on median follow-up of 36 months. By this time, 77 men assigned lutetium Lu 177 vipivotide tetraxetan, 70 assigned cabazitaxel, and 55 of those who had been excluded after PSMA/FDG-PET had died.
PFS remained “strongly in favor” of lutetium Lu 177 vipivotide tetraxetan (HR = 0.62; 95% CI, 0.45-0.85).
Researchers reported no statistically significant difference in OS between the lutetium Lu 177 vipivotide tetraxetan and cabazitaxel groups (restricted mean survival time, 19.1 months vs. 19.6 months; HR = 0.97; 95% CI, 0.7-1.4).
Investigators observed no new safety signals with lutetium Lu 177 vipivotide tetraxetan during the longer follow-up.
Subsequent treatments among men assigned lutetium Lu 177 vipivotide tetraxetan included additional lutetium Lu 177 vipivotide tetraxetan (n = 5) and cabazitaxel (n = 32). Subsequent treatments among those assigned cabazitaxel included additional cabazitaxel (n = 21) and lutetium Lu 177 vipivotide tetraxetan (n = 20).
Hofman and colleagues also assessed OS among 61 men who met all trial inclusion/exclusion criteria but ultimately were excluded due to low PSMA expression or discordant PSMA/FDG-PET results.
Results showed significantly longer survival among randomly assigned patients than those who failed initial screening (restricted mean survival time, 18.8 months vs. 11 months).
Strengths of the trial include its prospective, randomized, multicenter design, its 3-year follow-up and use of an active control arm, Hofman said.
Limitations included the fact post-protocol crossover confounded OS, and that the trial was underpowered to assess OS as a secondary endpoint, he said.
“[Lutetium Lu 177 vipivotide tetraxetan] has similar OS to cabazitaxel — a proven life-prolonging therapy — but with fewer adverse events and better patient-reported outcomes,” Hofman said during a presentation. “But we should be clear that [lutetium Lu 177 vipivotide tetraxetan] shows greater activity, and that’s not just confined to PSA response rates. We see it with radiographic PFS and RECIST.”
Perspective
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Kevin Ginsburg, MD, MS
Hofman and colleagues reported the OS outcomes of patients with metastatic castration-resistant prostate cancer previously treated with docetaxel who were randomly assigned to the theragnostic agent lutetium Lu 177 vipivotide tetraxetan or cabazitaxel. Despite a superior PSA response, improvement in PFS and less toxicity seen with lutetium Lu 177 vipivotide tetraxetan, as reported in their previous publication, there was no significant difference in OS seen in this current analysis. It should be noted there was significant crossover between groups, as approximately 20% of patients in the cabazitaxel arm subsequently received lutetium Lu 177 vipivotide tetraxetan and approximately 32% of those assigned lutetium Lu 177 vipivotide tetraxetan subsequently receiving cabazitaxel.
Although this study did not demonstrate an improvement in OS with lutetium Lu 177 vipivotide tetraxetan, one cannot discount the very important finding of improved quality of life compared with cabazitaxel as noted in their previous publication. Considering the advanced and incurable nature of the disease for the men enrolled in this study, there certainly seems to be an emerging role for lutetium Lu 177 vipivotide tetraxetan to maximize not only quantity but — importantly — quality of life for men with metastatic castration-resistant prostate cancer with progression after docetaxel.
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Hofman MS, et al. Abstract 5000. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
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