Radiolabeled Lutetium-177 offers higher PSA response versus cabazitaxel in metastatic castration-resistant prostate cancer

1. Radiolabeled Lutetium-177 offered greater PSA response versus current standard of care, cabazitaxel.

2. Fewer grade 3-4 adverse events occurred in patients treated with Lutetium-177 compared to cabazitaxel.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Although metastatic castration-resistant prostate cancer (mCRPC) is incurable, there exists several treatment options known to prolong overall survival. One such treatment, cabazitaxel, is usually used following treatment with docetaxel in non-responsive mCRPC. A new type of treatment involving radiolabeled molecules engineered to bind to prostate-specific membrane antigen have recently been introduced. One such molecule, Lutetium-177, has previously shown promising results in a phase 2 trial of 50 men with mCRPC. This non-blinded, randomized phase 2 trial sought to compare the activity and safety profile of Lutetium-177 vs. cabazitaxel in patients with mCRPC whose next treatment option involved cabazitaxel. Overall, a prostate-specific antigen (PSA) reduction of 50% or more was seen more often in the Lutetium-177 group; those assigned to Lutetium-177 also had delayed progression compared with cabazitaxel. In those with disease measurable by RECIST criteria, objective response rate (ORR) was greater in those receiving Lutetium-177. In addition, a fewer number of grade 3-4 adverse events were observed in the Lutetium-177 group: grade 3-4 thrombocytopenia was more common with those taking Lutetium-177, whereas grade 3-4 neutropenia was less common. While these results are promising, however, it is important to keep in mind that this study was not blinded; furthermore, the main outcomes of this study were primarily focused on biological markers (such as PSA response) rather than clinical outcomes such as overall survival. Indeed, longer follow-up time is required before any meaningful conclusions can be drawn.

Click to read the study in The Lancet

Click to read an accompanying editorial in The Lancet

Relevant Reading: PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617

In-Depth [randomized controlled trial]: This multicenter, randomized, nonblinded phase 2 trial assigned 200 patients with mCRPC to receive either Lutetium-177 or cabazitaxel at 11 centers in Australia. The primary outcome of this study was PSA response rate (proportion of participants with PSA reduction ≥ 50% from baseline). Secondary endpoints involved progression-free survival and objective response rate. Overall, more men in the Lutetium-177 group achieved a PSA response rate ≥ 50% vs. cabazitaxel (66% vs. 37%, p<0.0001). Fewer progression events were noted in the Lutetium-177 group (90 vs. 83, respectively) and there was delayed progression in the former group versus cabazitaxel (Hazard ratio=0.63 [95% CI=0.46-0.86, p=0.0028). In those with RECIST-measurable disease, objective response rate was greater in those taking Lutetium-177 (relative risk = 2.12 [95% CI = 1.10-4.08], p=0.019). Fewer grade 3-4 adverse events occurred in those taking Lutetium-177 vs. cabazitaxel (33% vs. 53%). Patients also reported objective improvements in quality of life and symptoms when taking Lutetium-177 vs. cabazitaxel with respect to diarrhea (p<0.0001), fatigue (p=0.027), social functioning (p=0.03) and insomnia (p=0.023).

Image: PD

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