@article {Barber955, author = {Thomas W. Barber and Aviral Singh and Harshad R. Kulkarni and Karin Niepsch and Baki Billah and Richard P. Baum}, title = {Clinical Outcomes of 177Lu-PSMA Radioligand Therapy in Earlier and Later Phases of Metastatic Castration-Resistant Prostate Cancer Grouped by Previous Taxane Chemotherapy}, volume = {60}, number = {7}, pages = {955--962}, year = {2019}, doi = {10.2967/jnumed.118.216820}, publisher = {Society of Nuclear Medicine}, 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.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/60/7/955}, eprint = {https://jnm.snmjournals.org/content/60/7/955.full.pdf}, journal = {Journal of Nuclear Medicine} }