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Bending the Curve Trial by Trial
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VISION

177Lu-PSMA-617 plus protocol-permitted standard care versus standard care alone in PSMA-positive metastatic castration-resistant prostate cancer

Phase 3N = 831NCT03511664

Population
Metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor-pathway inhibitor and one or two taxane regimens, with PSMA-positive 68Ga-PSMA-11 PET-CT; 831 of 1179 screened patients were randomised (the registry record lists 861)
Design
International, open-label phase 3 trial; randomisation 2:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) plus protocol-permitted standard care, or standard care alone. Protocol-permitted standard care excluded chemotherapy, immunotherapy, radium-223 and investigational drugs. Alternate primary endpoints were imaging-based progression-free survival and overall survival. Imaging-based PFS was analysed in an analysis set of the 581 patients randomised on or after 5 March 2019 (385 and 196), after the primary analysis was amended following high withdrawal from the control group at some sites; overall survival was analysed in all 831 randomised patients.
Primary endpoint
rPFS, OS
Arms
  • 177Lu-PSMA-617 plus standard care (experimental, n = 551): 177Lu-PSMA-617 7.4 GBq every 6 weeks for four to six cycles, plus protocol-permitted standard care
  • Standard care alone (control, n = 280): Protocol-permitted standard care (no chemotherapy, immunotherapy, radium-223 or investigational drugs)
People
Sartor O
rPFSHR 0.4Δ median rPFS+5.3 monthsOSHR 0.62 (95% CI 0.52–0.74)Δ median OS+4 months
Show the numbers
Results reported for VISION
EndpointAnalysis177Lu-PSMA-617 plus standard careStandard care aloneEffect
rPFSImaging-based PFS analysis set: patients randomised on or after 5 March 2019 (n=581; 385 with 177Lu-PSMA-617 plus standard care, 196 with standard care alone)Imaging-based progression-free survival (alternate primary endpoint)primarySartor 2021median 8.7 monthsmedian 3.4 monthsHR 0.4P<0.001Hazard ratio for progression or death 0.40 with a 99.2% CI of 0.29 to 0.57 (published interval is not a 95% CI; significance level 0.008). Analysed in the 581-patient analysis set, not all 831 randomised; results were similar in an ad hoc analysis of all randomised patients. Trial-wide median follow-up was 20.9 months.
OSAll randomised patients (n=831)primarymedian follow-up 20.9 monthsSartor 2021median 15.3 monthsmedian 11.3 monthsHR 0.62 (95% CI 0.52–0.74)P<0.001Alternate primary endpoint; hazard ratio for death. Analysed in all 831 randomised patients (the full text reports 15.3 vs 11.3 months for all 831).
Results reported for VISION
EndpointAnalysis177Lu-PSMA-617 plus standard careStandard care aloneEffect
rPFSImaging-based PFS analysis set: patients randomised on or after 5 March 2019 (n=581; 385 with 177Lu-PSMA-617 plus standard care, 196 with standard care alone)Imaging-based progression-free survival (alternate primary endpoint)primarySartor 2021median 8.7 monthsmedian 3.4 monthsHR 0.4P<0.001Hazard ratio for progression or death 0.40 with a 99.2% CI of 0.29 to 0.57 (published interval is not a 95% CI; significance level 0.008). Analysed in the 581-patient analysis set, not all 831 randomised; results were similar in an ad hoc analysis of all randomised patients. Trial-wide median follow-up was 20.9 months.
OSAll randomised patients (n=831)primarymedian follow-up 20.9 monthsSartor 2021median 15.3 monthsmedian 11.3 monthsHR 0.62 (95% CI 0.52–0.74)P<0.001Alternate primary endpoint; hazard ratio for death. Analysed in all 831 randomised patients (the full text reports 15.3 vs 11.3 months for all 831).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.620.52–0.74
Illustrative — modelled from reported values, not trial data. rPFS, primary.
0%25%50%75%100%05101520Months (modelled)
  • 177Lu-PSMA-617 plus standard care (experimental)
  • Standard care alone (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
Months177Lu-PSMA-617 plus standard careStandard care alone
0100.0%100.0%
567.1%36.1%
1141.6%10.6%
1627.9%3.8%
2217.3%1.1%
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0102030Months (modelled)
  • 177Lu-PSMA-617 plus standard care (experimental)
  • Standard care alone (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
Months177Lu-PSMA-617 plus standard careStandard care alone
0100.0%100.0%
1063.6%54.2%
1942.3%31.2%
2926.9%16.9%
3817.9%9.7%
Primary publication: Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021;385(12):1091-1103. PubMedDOI

Appears in

Sources

  1. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021;385(12):1091-1103.

    PubMedDOI