Clinical outcomes of 177Lu-PSMA radioligand therapy in earlier and later phases of metastatic castration-resistant prostate cancer grouped by previous taxane chemotherapy

Thomas W. Barber, Aviral Singh, Harshad R. Kulkarni, Karin Niepsch, Baki Billah, Richard P. Baum

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Abstract

177Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy using PSMA-617 and PSMA-I&T ligands (177Lu-PRLT) is an emerging treatment in metastatic castration-resistant prostate cancer (mCRPC). This retrospective study evaluates clinical outcomes of 177Lu-PRLT in earlier and later phases of mCRPC grouped by previous taxane chemotherapy. Methods: A retrospective analysis was performed on 167 patients with mCRPC who underwent 177Lu-PRLT between March 2013 and December 2016. Patients were classified as either taxane chemotherapy pretreated (T-pretreated) or naïve (T-naïve) depending on whether they had received taxane-based chemotherapy prior to 177Lu-PRLT. Clinical outcome for T-pretreated and T-naïve patients was assessed by overall survival (OS), radiographic progression-free survival, and prostate-specific antigen (PSA) response rate. Univariate and multivariable analyses were performed for both T-pretreated and T-naïve patients to determine predictors of outcome. Toxicity was categorized by the Common Terminology Criteria for Adverse Events (version 4.03). Results: Of the 167 patients treated with 177Lu-PRLT, 83 were T-pretreated and 84 were T-naïve. At baseline, T-pretreated patients had overall poorer performance status, a higher prevalence of bone metastases, higher PSA levels, lower hemoglobin levels, higher alkaline phosphatase (ALP) levels and had received more additional therapies compared with T-naïve patients. Median OS was 10.7 mo for T-pretreated patients and 27.1 mo for T-naïve patients. Median radiographic progression-free survival was 6.0 mo for T-pretreated patients and 8.8 mo for T-naïve patients. PSA response assessment was evaluable in 132 patients and seen in 25 of 62 (40%) T-pretreated patients and 40 of 70 (57%) T-naïve patients. Significant determinates of inferior OS in multivariable analysis for T-pretreated patients were poorer performance status, lower cumulative administered activity, and lower baseline hemoglobin. Higher baseline alkaline phosphatase was the only significant determinate of inferior OS in multivariable analysis for T-naïve patients. Overall 177Lu-PRLT was safe, with minimal adverse effects evident during follow-up in both T-pretreated and T-naïve patients. Conclusion: 177Lu-PRLT is a promising therapy in mCRPC, with encouraging outcomes and minimal associated toxicity seen in both our T-naïve and heavily pretreated patient cohorts.

Original languageEnglish
Pages (from-to)955-962
Number of pages8
JournalJournal of Nuclear Medicine
Volume60
Issue number7
DOIs
Publication statusPublished - 1 Jul 2019

Keywords

  • Lu-PRLT
  • Chemotherapy
  • Lutetium
  • Prostate-specific membrane antigen
  • Radioligand therapy

Cite this

@article{30ab56316a0e4404bffd002cb8ca69c9,
title = "Clinical outcomes of 177Lu-PSMA radioligand therapy in earlier and later phases of metastatic castration-resistant prostate cancer grouped by previous taxane chemotherapy",
abstract = "177Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy using PSMA-617 and PSMA-I&T ligands (177Lu-PRLT) is an emerging treatment in metastatic castration-resistant prostate cancer (mCRPC). This retrospective study evaluates clinical outcomes of 177Lu-PRLT in earlier and later phases of mCRPC grouped by previous taxane chemotherapy. Methods: A retrospective analysis was performed on 167 patients with mCRPC who underwent 177Lu-PRLT between March 2013 and December 2016. Patients were classified as either taxane chemotherapy pretreated (T-pretreated) or na{\"i}ve (T-na{\"i}ve) depending on whether they had received taxane-based chemotherapy prior to 177Lu-PRLT. Clinical outcome for T-pretreated and T-na{\"i}ve patients was assessed by overall survival (OS), radiographic progression-free survival, and prostate-specific antigen (PSA) response rate. Univariate and multivariable analyses were performed for both T-pretreated and T-na{\"i}ve patients to determine predictors of outcome. Toxicity was categorized by the Common Terminology Criteria for Adverse Events (version 4.03). Results: Of the 167 patients treated with 177Lu-PRLT, 83 were T-pretreated and 84 were T-na{\"i}ve. At baseline, T-pretreated patients had overall poorer performance status, a higher prevalence of bone metastases, higher PSA levels, lower hemoglobin levels, higher alkaline phosphatase (ALP) levels and had received more additional therapies compared with T-na{\"i}ve patients. Median OS was 10.7 mo for T-pretreated patients and 27.1 mo for T-na{\"i}ve patients. Median radiographic progression-free survival was 6.0 mo for T-pretreated patients and 8.8 mo for T-na{\"i}ve patients. PSA response assessment was evaluable in 132 patients and seen in 25 of 62 (40{\%}) T-pretreated patients and 40 of 70 (57{\%}) T-na{\"i}ve patients. Significant determinates of inferior OS in multivariable analysis for T-pretreated patients were poorer performance status, lower cumulative administered activity, and lower baseline hemoglobin. Higher baseline alkaline phosphatase was the only significant determinate of inferior OS in multivariable analysis for T-na{\"i}ve patients. Overall 177Lu-PRLT was safe, with minimal adverse effects evident during follow-up in both T-pretreated and T-na{\"i}ve patients. Conclusion: 177Lu-PRLT is a promising therapy in mCRPC, with encouraging outcomes and minimal associated toxicity seen in both our T-na{\"i}ve and heavily pretreated patient cohorts.",
keywords = "Lu-PRLT, Chemotherapy, Lutetium, Prostate-specific membrane antigen, Radioligand therapy",
author = "Barber, {Thomas W.} and Aviral Singh and Kulkarni, {Harshad R.} and Karin Niepsch and Baki Billah and Baum, {Richard P.}",
year = "2019",
month = "7",
day = "1",
doi = "10.2967/jnumed.118.216820",
language = "English",
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Clinical outcomes of 177Lu-PSMA radioligand therapy in earlier and later phases of metastatic castration-resistant prostate cancer grouped by previous taxane chemotherapy. / Barber, Thomas W.; Singh, Aviral; Kulkarni, Harshad R.; Niepsch, Karin; Billah, Baki; Baum, Richard P.

In: Journal of Nuclear Medicine, Vol. 60, No. 7, 01.07.2019, p. 955-962.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Clinical outcomes of 177Lu-PSMA radioligand therapy in earlier and later phases of metastatic castration-resistant prostate cancer grouped by previous taxane chemotherapy

AU - Barber, Thomas W.

AU - Singh, Aviral

AU - Kulkarni, Harshad R.

AU - Niepsch, Karin

AU - Billah, Baki

AU - Baum, Richard P.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 177Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy using PSMA-617 and PSMA-I&T ligands (177Lu-PRLT) is an emerging treatment in metastatic castration-resistant prostate cancer (mCRPC). This retrospective study evaluates clinical outcomes of 177Lu-PRLT in earlier and later phases of mCRPC grouped by previous taxane chemotherapy. Methods: A retrospective analysis was performed on 167 patients with mCRPC who underwent 177Lu-PRLT between March 2013 and December 2016. Patients were classified as either taxane chemotherapy pretreated (T-pretreated) or naïve (T-naïve) depending on whether they had received taxane-based chemotherapy prior to 177Lu-PRLT. Clinical outcome for T-pretreated and T-naïve patients was assessed by overall survival (OS), radiographic progression-free survival, and prostate-specific antigen (PSA) response rate. Univariate and multivariable analyses were performed for both T-pretreated and T-naïve patients to determine predictors of outcome. Toxicity was categorized by the Common Terminology Criteria for Adverse Events (version 4.03). Results: Of the 167 patients treated with 177Lu-PRLT, 83 were T-pretreated and 84 were T-naïve. At baseline, T-pretreated patients had overall poorer performance status, a higher prevalence of bone metastases, higher PSA levels, lower hemoglobin levels, higher alkaline phosphatase (ALP) levels and had received more additional therapies compared with T-naïve patients. Median OS was 10.7 mo for T-pretreated patients and 27.1 mo for T-naïve patients. Median radiographic progression-free survival was 6.0 mo for T-pretreated patients and 8.8 mo for T-naïve patients. PSA response assessment was evaluable in 132 patients and seen in 25 of 62 (40%) T-pretreated patients and 40 of 70 (57%) T-naïve patients. Significant determinates of inferior OS in multivariable analysis for T-pretreated patients were poorer performance status, lower cumulative administered activity, and lower baseline hemoglobin. Higher baseline alkaline phosphatase was the only significant determinate of inferior OS in multivariable analysis for T-naïve patients. Overall 177Lu-PRLT was safe, with minimal adverse effects evident during follow-up in both T-pretreated and T-naïve patients. Conclusion: 177Lu-PRLT is a promising therapy in mCRPC, with encouraging outcomes and minimal associated toxicity seen in both our T-naïve and heavily pretreated patient cohorts.

AB - 177Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy using PSMA-617 and PSMA-I&T ligands (177Lu-PRLT) is an emerging treatment in metastatic castration-resistant prostate cancer (mCRPC). This retrospective study evaluates clinical outcomes of 177Lu-PRLT in earlier and later phases of mCRPC grouped by previous taxane chemotherapy. Methods: A retrospective analysis was performed on 167 patients with mCRPC who underwent 177Lu-PRLT between March 2013 and December 2016. Patients were classified as either taxane chemotherapy pretreated (T-pretreated) or naïve (T-naïve) depending on whether they had received taxane-based chemotherapy prior to 177Lu-PRLT. Clinical outcome for T-pretreated and T-naïve patients was assessed by overall survival (OS), radiographic progression-free survival, and prostate-specific antigen (PSA) response rate. Univariate and multivariable analyses were performed for both T-pretreated and T-naïve patients to determine predictors of outcome. Toxicity was categorized by the Common Terminology Criteria for Adverse Events (version 4.03). Results: Of the 167 patients treated with 177Lu-PRLT, 83 were T-pretreated and 84 were T-naïve. At baseline, T-pretreated patients had overall poorer performance status, a higher prevalence of bone metastases, higher PSA levels, lower hemoglobin levels, higher alkaline phosphatase (ALP) levels and had received more additional therapies compared with T-naïve patients. Median OS was 10.7 mo for T-pretreated patients and 27.1 mo for T-naïve patients. Median radiographic progression-free survival was 6.0 mo for T-pretreated patients and 8.8 mo for T-naïve patients. PSA response assessment was evaluable in 132 patients and seen in 25 of 62 (40%) T-pretreated patients and 40 of 70 (57%) T-naïve patients. Significant determinates of inferior OS in multivariable analysis for T-pretreated patients were poorer performance status, lower cumulative administered activity, and lower baseline hemoglobin. Higher baseline alkaline phosphatase was the only significant determinate of inferior OS in multivariable analysis for T-naïve patients. Overall 177Lu-PRLT was safe, with minimal adverse effects evident during follow-up in both T-pretreated and T-naïve patients. Conclusion: 177Lu-PRLT is a promising therapy in mCRPC, with encouraging outcomes and minimal associated toxicity seen in both our T-naïve and heavily pretreated patient cohorts.

KW - Lu-PRLT

KW - Chemotherapy

KW - Lutetium

KW - Prostate-specific membrane antigen

KW - Radioligand therapy

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U2 - 10.2967/jnumed.118.216820

DO - 10.2967/jnumed.118.216820

M3 - Article

VL - 60

SP - 955

EP - 962

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

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ER -