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¹⁷⁷Lu-PSMA-617 Superior to Cabazitaxel in Metastatic Prostate Cancer

Web Exclusives - Prostate Cancer
Phoebe Starr

Cabazitaxel (Jevtana) is approved as third-line therapy for patients with metastatic castration-resistant prostate cancer (CRPC) after treatment with docetaxel and an androgen receptor inhibitor. A new phase 2 clinical trial shows that the radionuclide therapy that targets the prostate-specific membrane antigen (PSMA), 177Lu-PSMA-617, reduced the risk for disease progression or death by 37% compared with cabazitaxel in men with previously treated metastatic CRPC. Moreover, the TheraP study showed that patients who received 177Lu-PSMA-617 had fewer side effects and improved quality of life compared with patients who received cabazitaxel.

TheraP results were presented at the 2021 ASCO Genitourinary Cancers Symposium and simultaneously published (Hofman MS, et al. Lancet. 2021;397:797-804).

Survival data are not yet mature, but experts said that 177Lu-PSMA-617 is poised to become a third-line option if phase 3 studies are confirmatory.

177Lu-PSMA-617 is a promising alternative to cabazitaxel, with significantly higher activity and fewer grades 3 and 4 events and similar effects on global health status and improvements in multiple patient-reported outcome domains. 177Lu-PSMA-617 represents a new class of effective therapy for men with castration-resistant prostate cancer,” said lead investigator Michael S. Hofman, MBBS, FRACP, Director, Prostate Cancer Theranostics and Imaging Centre of Excellence, Melbourne, Australia.

PSMA-Targeting Therapy

177Lu-PSMA-617 is one of several investigational therapies that target PSMA, which is expressed on the surface of metastatic prostate cancer cells but not on normal tissue.

The investigator-initiated phase 2 TheraP trial included 200 men with metastatic CRPC who were randomized in a 1:1 ratio to 177Lu-PSMA-617 intravenously every 6 weeks for up to 6 cycles (starting dose 8.5 GBq, decreasing 0.5 GBq each cycle) or to cabazitaxel (20 mg/m2 intravenously for up to 10 cycles). All patients had previously received docetaxel.

The median patient age was 72 years; 91% were previously treated with abiraterone (Zytiga), enzalutamide (Xtandi), or both; and approximately 95% of patients had Eastern Cooperative Oncology Group performance status score of 0 to 1.

The study’s primary end point was a ≥50% reduction in prostate-specific antigen from baseline, which was met by 66% of patients in the 177Lu-PSMA-617 arm versus 37% in the cabazitaxel arm (P <.0001). The objective response rate was 49% with 177Lu-PSMA-617 versus 24% with cabazitaxel.

Although at 5 months, both arms had the same percentage of patients who had radiographic progression-free survival (PFS), at 12 months, radiographic PFS was 19% with 177Lu-PSMA-617 versus 3% with cabazitaxel. Pain scores were reduced in 60% of patients versus 43%, respectively.

Grade 3 or 4 adverse events were 33% with 177Lu-PSMA-617 versus 53% with cabazitaxel. The most common grades 3 and 4 events in the 177Lu-PSMA-617 arm and the cabazitaxel arm, respectively, were neutropenia (4% vs 13%), thrombocytopenia (11% vs 0%), anemia (8% in each arm), diarrhea (1% vs 5%), and fatigue (5% vs 4%).

According to the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30, 177Lu-PSMA-617 significantly improved the domains of social functioning, fatigue, insomnia, and diarrhea and all other domains scored numerically higher. Patients who received 177Lu-PSMA-617 had a lower incidence of skin rash, palmar/plantar soreness, dysgeusia, dizziness, urinary symptoms, and diarrhea versus patients who received cabazitaxel.

The deterioration-free survival (defined as time to >10-point deterioration on EORTC QLQ-C30 in global health status, disease progression, or death) rate was improved at 6 months and 12 months with 177Lu-PSMA-617 compared with cabazitaxel: 29% versus 13%, respectively. The 12-month rates were 21% versus 1%, respectively.

At least 4 other PSMA-targeted drugs are in various stages of development. 177Lu-PSMA-617 is the furthest along, and the ongoing phase 3 VISION trial is comparing 177Lu-PSMA-617 to cabazitaxel. Results are expected later in 2021.

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Last modified: August 30, 2021