Kim Chi, MD, on sequencing 177Lu-PSMA-617 and docetaxel in mCRPC

In the following interview, conducted at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, Kim N. Chi, MD, discussed findings from a planned secondary analysis of the phase 2 PLUDO trial,¹ which evaluated ¹⁷⁷Lu-PSMA-617 (lutetium PSMA-617) vs docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease had progressed on an androgen receptor pathway inhibitor (ARPI). Chi is a medical oncologist at BC Cancer Vancouver Center and a professor of medicine at the University of British Columbia.

The Canadian Cancer Trials Group PR.21 (PLUDO) study was designed to compare ¹⁷⁷Lu-PSMA-617 with docetaxel, a treatment widely considered a standard option following progression on ARPI therapy. The randomized phase 2 trial enrolled 199 patients and assessed radiographic progression-free survival (rPFS) as its primary end point. Patients were permitted to cross over to the alternate treatment after progression, allowing investigators to evaluate treatment sequencing. Initial results, previously presented at the 2025 European Society for Medical Oncology Congress, showed no significant difference in rPFS between the 2 treatment arms (HR, 1.01; 95% CI, 0.77-1.31). However, patients randomized to receive docetaxel first appeared to have longer overall survival (HR, 1.64; 95% CI, 1.14-2.35),² prompting investigators to explore whether crossover patterns may have influenced that finding.

In the secondary analysis presented, at the 2026 American Society of Clinical Oncology Annual Meeting, investigators examined the imbalance in crossover between treatment arms. Approximately 40% of patients who received ¹⁷⁷Lu-PSMA-617 first crossed over to docetaxel (42 of 100), compared with more than 60% of patients who received docetaxel first and subsequently crossed over to lutetium therapy (62 of 99). To better understand this discrepancy, researchers evaluated quality-of-life outcomes and adverse events at the time of first progression. Patients progressing on lutetium therapy reported higher FACT-P quality-of-life scores than those progressing on docetaxel (114 vs 103), while adverse event rates were similar between groups. These findings suggested that poorer quality of life or greater toxicity were unlikely explanations for the lower crossover rate from lutetium therapy to chemotherapy.

The analysis also evaluated outcomes among patients who ultimately received both treatments. According to Chi, sequence did not appear to influence efficacy: Patients treated with lutetium followed by docetaxel experienced similar rPFS and OS as those who received docetaxel followed by lutetium. These findings support the use of both therapies in patients with mCRPC after ARPI progression and suggest that the previously observed overall survival advantage for initial docetaxel treatment was likely driven by the imbalance in crossover rather than a true sequencing effect.

REFERENCES

1. Chi KN, Saad F, Ding K, et al. Canadian Cancer Trials Group (CCTG) study PR21 (PLUDO): Results of crossover treatment from a randomized trial of ¹⁷⁷Lu-PSMA-617 (LuP) vs docetaxel (DOC) in patients with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2026 (suppl 16; abstr 5019). doi:10.1200/JCO.2026.44.16_suppl.5019

2. Chi KN, Saad F, Ding KU, et al. A randomized phase II study of 177Lu-PSMA-617 vs docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) and PSMA-positive disease: Canadian Cancer Trials Group (CCTG) study PR.21. Presented at: 2025 European Society for Medical Oncology Congress; October 17-21, 2025; Berlin, Germany. LBA89