Previously, the phase 3 VISION trial demonstrated an improved radiographic progression-free (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer patients receiving [177Lu]Lu-PSMA-617 plus standard of care (SOC), compared to those receiving SOC alone. Additional results from this trial, recently published in Lancet Oncology, reveal that [177Lu]Lu-PSMA-617 also delays the time to a worsening quality of life and the time to the development of skeletal events. These findings further support the use of [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment.
Despite the availability of various therapies that can delay disease progression and extend survival, metastatic castration-resistant prostate cancer remains to be incurable and fatal. Prostate-specific membrane antigen (PSMA) is a transmembrane glutamate carboxypeptidase that is highly expressed in prostate cancer cells. The radioligand therapy lutetium-177 (177Lu)–PSMA-617 (vipivotide tetraxetan) delivers beta-particle radiation selectively to PSMA-positive cells and the surrounding microenvironment. This agent has been associated with encouraging biochemical and radiographic response rates, reduced pain, and low toxicity in patients with progression of metastatic castration-resistant prostate cancer after standard therapy. In the phase 3 VISION trial, [177Lu]Lu-PSMA-617 was shown to improve the radiographic progression-free (PFS) and overall survival (OS) when added to standard of care (SOC) in patients with metastatic castration-resistant prostate cancer. Additional health-related quality of life (HRQOL), pain, and symptomatic skeletal event results of this trial were recently reported.
The phase 3 VISION trial was conducted at 84 cancer centres in nine countries in North America and Europe. Eligible patients were aged 18 years or older, had progressive PSMA-positive metastatic castration-resistant prostate cancer, an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 and had previously received at least one androgen receptor pathway inhibitor and one or two taxane-containing regimens. In total, 831 patients were randomly assigned (2:1) to receive either [177Lu]Lu-PSMA-617 plus protocol-permitted standard of care (n=385) or SOC alone (n=196). The primary endpoints were radiographic PFS and OS, which have already been reported. In this new report, the secondary endpoints are presented, including time to first symptomatic skeletal event and HRQOL assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-5L, and pain assessed with the Brief Pain Inventory-Short Form (BPI-SF).
The results of the study showed significant improvements in several key measures in patients receiving [177Lu]Lu-PSMA-617 compared to those receiving SOC alone. The median time to first symptomatic skeletal event or death was 11.5 months in the [177Lu]Lu-PSMA-617 group as compared to 6.8 months in the control group (HR[95%CI]: 0.50[0.40-0.62]). Moreover, the [177Lu]Lu-PSMA-617 group demonstrated delayed time to worsening in various QoL domains, including FACT-P score (HR: 0.54 [0.45-0.66]), BPI-SF pain intensity score (HR: 0.52[0.42-0.63), and EQ-5D-5L utility score (HR: 0.65[0.54-0.78]). Grade 3 or 4 haematological adverse events included decreased haemoglobin (15% vs. 6% of patients in the [177Lu]Lu-PSMA-617 and control groups, respectively), lymphocyte concentrations (51% vs. 19%), and platelet counts (9% vs. 2%). Treatment-related adverse events leading to death occurred in five (1%) patients who received [177Lu]Lu-PSMA-617 (pancytopenia [n=2], bone marrow failure [n=1], subdural haematoma [n=1], and intracranial haemorrhage [n=1]) and no patients who received SOC only.
In conclusion, compared to SOC alone, [177Lu]Lu-PSMA-617 plus SOC delayed the time to a HRQOL worsening and delayed the time to the development of a first symptomatic skeletal event. These findings support the use of [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment.
Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(6):597-610.