Clinical Summary:

• Design/Population: Canadian Cancer Trials Group PR21 PLUTO trial evaluating lutetium-177 PSMA therapy versus docetaxel in patients with PSMA PET-positive metastatic castration-resistant prostate cancer progressing after an androgen receptor pathway inhibitor. 
• Key Outcomes: Prior analyses showed similar radiographic progression-free survival between treatment arms but an overall survival advantage favoring docetaxel, potentially due to crossover imbalance. A preplanned crossover analysis demonstrated no significant differences in progression-free or overall survival among patients who ultimately received both treatments.
• Clinical Relevance: These findings suggest that access to both docetaxel and lutetium-177 PSMA therapy may be more important than the sequence in which they are administered.

Kim Chi, MD, BC Cancer Vancouver Centre, Vancouver, Canada, discusses results from a preplanned crossover analysis of the PR21 PLUTO trial evaluating treatment sequencing in PSMA-positive metastatic castration-resistant prostate cancer. The study previously reported similar radiographic progression-free survival between lutetium-177 PSMA therapy and docetaxel, with an apparent overall survival advantage favoring docetaxel.

The updated analysis found no differences in outcomes among patients who crossed over and ultimately received both treatments, regardless of whether docetaxel or lutetium-177 PSMA therapy was administered first. These findings support the incorporation of both treatment modalities after ARPI progression and suggest that ensuring patient access to both therapies may have a greater impact than prioritizing one sequence over another.

Dr Chi presented these results at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

Transcript: 

Hi, I'm Dr Kim Chi, a medical oncologist at BC Cancer Vancouver Centre. I'm also affiliated with the Vancouver Prostate Centre and the University of British Columbia. At this ASCO, I'm presenting results from the Canadian Cancer Trials Group PR21 PLUTO study.

In this study, we enrolled patients with metastatic castration-resistant prostate cancer who were progressing after an ARPI and were PSMA PET–positive. Patients were randomized to receive either lutetium-177 PSMA radioligand therapy or docetaxel at standard doses and schedules. We previously reported the primary end point, which was radiographic progression-free survival with first treatment. There was no difference between lutetium and docetaxel for that end point. However, what did emerge was an overall survival advantage for patients randomized to docetaxel. We believe this may be related to an imbalance in crossover, with approximately 60% of patients crossing over from docetaxel to lutetium, compared with only about 40% crossing over from lutetium to docetaxel.

To explore this further, I presented a preplanned analysis of crossover therapy. The first thing we examined was the potential reason why patients did not cross over. At the time of first radiographic progression, we looked at quality-of-life measures and adverse events. Quality of life actually favored patients who had initially received lutetium. We also looked at grade 3 and 4 adverse events, which were roughly similar between the two treatment arms. So the lower crossover rate from lutetium to docetaxel does not appear to be explained by differences in quality of life or toxicity.

We then looked at outcomes among patients who crossed over and ultimately received both treatments. There was no difference between patients who received lutetium followed by docetaxel and those who received docetaxel followed by lutetium, either in terms of radiographic progression-free survival or overall survival. Treatment-emergent adverse events and treatment-related adverse events were consistent with what has previously been reported for both therapies.

Taken together, and considering all of the data from PR21 PLUTO, the study supports the use of either docetaxel alone or the sequential use of both docetaxel and lutetium in patients with metastatic castration-resistant prostate cancer progressing after an ARPI.

Source: 

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). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 5019.