Phase III VISION Study Shows 177Lu-PSMA-617 Significantly Improves Overall Survival and Radiographic Progression-Free Survival for Men with Metastatic Castration-Resistant Prostate Cancer

  • Men who received 177Lu-PSMA-617 plus best standard of care had a 38% reduction in risk of death (median OS benefit of 4 months) and a 60% reduction in the risk of radiographic disease progression or death (median rPFS benefit of 5 months) compared to best standard of care alone1
  • Significant improvement demonstrated in all key secondary endpoints, including time to first symptomatic skeletal event, overall response rate and disease control rate1
  • VISION study findings to be presented during 2021 ASCO plenary; regulatory submissions to US and EU Health Authorities on track for 2H21; two additional pivotal studies in earlier lines of treatment for metastatic prostate cancer to start 1H21, goal to move into earlier stages of disease
  • Novartis commitment to leadership in radioligand therapy (RLT) further strengthened by recent partnerships and investments; more than 15 ongoing research and discovery programs to identify and accelerate next wave of RLTs for cancer

San Francisco, CA (UroToday.com) -- Novartis announced that results of the Phase III VISION study evaluating 177Lu-PSMA-617, a targeted radioligand therapy, plus best standard of care (SOC) demonstrated significant improvement in overall survival (OS) compared to SOC alone, in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).1 The difference in OS between study arms was statistically significant (one-sided p<0.001), with an estimated 38% reduction in risk of death in the 177Lu-PSMA-617 arm (n=551) compared to the best standard of care only arm (n=280) (hazard ratio: 0.62 with 95% confidence interval (CI): (0.52, 0.74)).1 These results will be presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting plenary session on June 6.


Patients receiving 177Lu-PSMA-617 also demonstrated a statistically significant (one-sided p<0.001) 60% risk reduction for radiographic progression-free survival or death (rPFS), compared to the best standard of care only arm (hazard ratio: 0.40 with 99.2% CI: (0.29 0.57)).1 There was a higher rate of drug-related treatment-emergent adverse events reported in the 177Lu-PSMA-617 treatment arm (85.3%) compared to standard of care alone (28.8%).1

Across both arms of the study, rates of treatment discontinuation associated with treatment-emergent adverse events occurred as follows: In the 177Lu-PSMA-617 plus standard of care (SOC) arm, 11.9% of patients discontinued 177Lu-PSMA-617 and 8.5% discontinued SOC; while in the SOC alone arm 7.8% of patients discontinued treatment.1


“Patients suffering from metastatic CRPC who have progressed through contemporary hormonal treatments and chemotherapy have few meaningful therapeutic options,” said Michael J. Morris, MD, who chaired the study’s Scientific Committee and is the Prostate Cancer Section Head, Genitourinary Oncology Service, Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center. “The study demonstrated that 177Lu-PSMA-617 improves disease progression and prolongs survival, which are key measures of clinical benefit in the mCRPC population. I am grateful to be a part of this study that may lead to additional therapeutic options for these patients.”
“Men with metastatic prostate cancer have an approximately 3 in 10 chance of surviving 5 years.2 These data from the first Phase III study of a radioligand therapy in this advanced prostate cancer setting confirm the potential of 177Lu-PSMA-617 targeted therapy to improve clinical outcomes,” said John Tsai, Head of Global Drug Development and Chief Medical Officer for Novartis. “Our comprehensive development program for this targeted therapy seeks to reach eligible patients with advanced prostate cancer, who express the PSMA biomarker.1,3-6 And, we won’t stop with prostate cancer, our team is exploring next-generation RLT across a number of tumor types.”

Two additional studies with 177Lu-PSMA-617 radioligand therapy in earlier lines of treatment for metastatic prostate cancer are planned to start in the first half of 2021, investigating potential clinical utility in the mCRPC pre-taxane setting (PSMAfore) and in the metastatic hormone-sensitive setting (PSMAddition).

Additional VISION data


Median OS (95% CI) for the 177Lu-PSMA-617 plus best standard of care arm in the VISION study was 15.3 months (14.2, 16.9), compared to 11.3 months (9.8, 13.5) in the best standard of care arm only.1 The median rPFS (99.2% CI) was 8.7 months (7.9, 10.8) for the 177Lu-PSMA-617 arm compared to 3.4 months (2.4, 4.0) for the best standard of care only arm.1

Key secondary endpoints were also met. The median time to first symptomatic skeletal event was 11.5 months (95% CI: 10.3, 13.2) in 177Lu-PSMA-617 arm compared to 6.8 months (95% CI: 5.2, 8.5) in the best standard of care only arm (hazard ratio: 0.50 (95%CI: 0.40, 0.62)); two-sided p-value: <0.001.1 Significant differences were also seen in overall response rate in patients with measurable or non-measurable disease at baseline (29.8% partial or complete response in the 177Lu-PSMA-617 arm compared to 1.7% partial response in the best standard of care only arm (two-sided p-value: <0.001)) and disease control rate (89.0% in 177Lu-PSMA-617 arm compared to 66.7% in the best standard of care only arm (two-sided p-value: <0.001)).1

Grade ≥3 drug-related treatment emergent adverse events occurred in 28.4% of the 177Lu-PSMA-617 arm compared to 3.9% in the best standard of care only arm.1 The most common treatment emergent adverse events regardless of drug relatedness (above 2% respectively for the 177Lu-PSMA-617 and best standard of care arm) were anemia (12.9% vs. 4.9%), thrombocytopenia (7.9% vs. 1%), lymphopenia (7.8% vs. 0.5%), fatigue (5.9% vs. 1.5%), urinary tract infection (3.8% vs 0.5%), neutropenia (3.4% vs 0.5%), hypertension (3.2% vs 1.5%), back pain (3.2% vs. 3.4%), acute kidney injury (3.0% vs 2.4%), leukopenia (2.5% vs. 0.5%), bone pain (2.5% vs. 2.4%), hematuria (2.5% vs 0.5%), and spinal cord compression (1.3% vs. 5.4%).1

Serious drug-related treatment-emergent adverse events occurred in 9.3% of patients in the 177Lu-PSMA-617 arm compared to 2.4% in the best standard of care only arm.1

References:

  1. Novartis Data on File
  2. SEER. Cancer stat facts: prostate cancer April 2021. [https://seer.cancer.gov/statfacts/html/prost.html]
  3. Hupe MC, Philippi C, Roth D, et al. Expression of prostate-specific membrane antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Front Oncol 2018;8:623
  4. Bostwick DG, Pacelli A, Blute M, et al. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 1998;82(11):2256–61
  5. Pomykala KL, Czernin J, Grogan TR, et al. Total-body 68Ga-PSMA-11 PET/CT for bone metastasis detection in prostate cancer patients: potential impact on bone scan guidelines. J Nucl Med 2020;61(3):405–11
  6. Sant GR, Knopf KB, Albala DM. Live-single-cell phenotypic cancer biomarkers-future role in precision oncology? NPJ Precision Oncology 2017;1(1):21

Source: AG, Novartis. 2021. "Novartis 177Lu-PSMA-617 Significantly Improves Overall Survival And Radiographic Progression-Free Survival For Men With Metastatic Castration-Resistant Prostate Cancer In Phase III VISION Study". Globenewswire News Room. 


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