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Exposure-adjusted safety analyses of the VISION phase 3 trial of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer.

Publication ,  Conference
Chi, KN; Adra, N; Garje, R; Michalski, JM; Lavalaye, J; Kempel, MM; Brackman, M; Perraud, K; Holder, G; Armstrong, AJ
Published in: Journal of Clinical Oncology
February 20, 2022

85 Background: In the VISION trial, targeted radioligand therapy with Lu-PSMA-617 significantly prolonged radiographic progression free survival (rPFS) and overall survival when added to standard of care (SoC) in patients with advanced prostate-specific membrane antigen (PSMA)-PET-positive metastatic castration-resistant prostate cancer. There was a higher incidence of treatment-emergent adverse events (TEAEs) with Lu-PSMA-617 + SoC vs SoC. However, treatment exposure was more than three times longer in the Lu-PSMA-617 + SoC arm and thus relative toxicity may have been overestimated. A post hoc analysis of the relationship between exposure and frequency of TEAEs was performed to facilitate comparison of rates between arms. Methods: In this international, open-label study, adult patients previously treated with ≥ 1 androgen receptor pathway inhibitors and 1–2 taxane regimens were randomized 2:1 to Lu-PSMA-617 (7.4 GBq Q6W, ≤ 6 cycles) + SoC or SoC. Safety was a secondary endpoint. TEAEs (regardless of causality) were reported from start of randomized treatment for up to 30 days after last treatment administration (including SoC) or 1 day before subsequent anticancer treatment, whichever occurred first. Overall TEAE incidence was adjusted for treatment exposure by calculating incidence per 100 patient treatment-years (PTY). The analysis was performed for the first occurrence of TEAEs. Results: Exposure-adjusted incidence of any grade, grade ≥ 3 and selected TEAEs are listed in the table. There was similar exposure-adjusted incidence of gastrointestinal events and fatigue and higher exposure-adjusted incidence of musculoskeletal and renal events with SoC compared with Lu-PSMA-617 + SoC suggesting an association with treatment exposure rather than Lu-PSMA-617. Dry mouth, dry eye and acute myelosuppression maintained a higher incidence, confirming relationship with Lu-PSMA-617 treatment. Conclusions: The adjusted safety analysis, accounting for a longer safety observation due to longer rPFS in patients receiving Lu-PSMA-617, reveals a comparable incidence of TEAEs between arms. This confirms a favorable risk/benefit profile of Lu-PSMA-617 added to SoC in this patient population. Clinical trial information: NCT03511664. [Table: see text]

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2022

Volume

40

Issue

6_suppl

Start / End Page

85 / 85

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chi, K. N., Adra, N., Garje, R., Michalski, J. M., Lavalaye, J., Kempel, M. M., … Armstrong, A. J. (2022). Exposure-adjusted safety analyses of the VISION phase 3 trial of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. In Journal of Clinical Oncology (Vol. 40, pp. 85–85). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2022.40.6_suppl.085
Chi, Kim N., Nabil Adra, Rohan Garje, Jeff M. Michalski, Jules Lavalaye, Mette Moe Kempel, Marcia Brackman, Kevin Perraud, Geoffrey Holder, and Andrew J. Armstrong. “Exposure-adjusted safety analyses of the VISION phase 3 trial of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer.” In Journal of Clinical Oncology, 40:85–85. American Society of Clinical Oncology (ASCO), 2022. https://doi.org/10.1200/jco.2022.40.6_suppl.085.
Chi KN, Adra N, Garje R, Michalski JM, Lavalaye J, Kempel MM, et al. Exposure-adjusted safety analyses of the VISION phase 3 trial of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2022. p. 85–85.
Chi, Kim N., et al. “Exposure-adjusted safety analyses of the VISION phase 3 trial of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer.Journal of Clinical Oncology, vol. 40, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2022, pp. 85–85. Crossref, doi:10.1200/jco.2022.40.6_suppl.085.
Chi KN, Adra N, Garje R, Michalski JM, Lavalaye J, Kempel MM, Brackman M, Perraud K, Holder G, Armstrong AJ. Exposure-adjusted safety analyses of the VISION phase 3 trial of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2022. p. 85–85.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2022

Volume

40

Issue

6_suppl

Start / End Page

85 / 85

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences