PSMA PET is a predictive biomarker in mCRPC progressing after docetaxel

In men with metastatic castration-resistant prostate cancer (mCRPC), high PSMA expression is predictive of a higher likelihood of favourable response to ¹⁷⁷Lu-PSMA-617 (LuPSMA) than cabazitaxel. In addition, a high volume of disease on ¹⁸FDG PET is prognostic for worse outcome regardless of treatment.

The TheraP trial (NCT03392428) showed that LuPSMA improved PSA ≥50% response rate (PSA50 RR), PSA progression-free survival (PFS), and radiographic PFS (rPFS) compared with cabazitaxel in mCRPC progressing after docetaxel [1]. In addition, it was hypothesised that a high PSMA expression would correlate to a better response to LuPSMA versus cabazitaxel, while a high FDG-positive tumour volume would correlate to a low response to either therapy. In other words, that PSMA PET would be a predictive biomarker and FDG PET a prognostic biomarker. Prof. Michael Hofman (Peter MacCallum Cancer Centre, Australia) presented the results of the analyses that explored this hypothesis [2].

Very high PSMA uptake on PSMA PET (SUVmean ≥10) was seen in 35/99 (35%) TheraP participants assigned to LuPSMA and 30/101 (30%) participants assigned to cabazitaxel. The odds of a response to LuPSMA versus cabazitaxel were significantly higher for men with SUVmean ≥10 compared with men with SUV <10 (OR 12.2 vs 2.2; P=0.03). In men with SUVmean ≥10, the PSA50 RR for LuPSMA versus cabazitaxel was 32/35 (91%) versus 14/30 (47%). In men with PSMA SUVmean <10, the PSA50 RR was 33/62 (52%) versus 23/71 (32%), respectively. The HR for PSA-PFS for LuPSMA versus cabazitaxel was 0.45 for SUVmean ≥10 versus 0.77 for SUVmean <10 (P=0.2).

High-volume metabolic disease on FDG PET (metabolic tumour volume [MTV] ≥200 mL) was seen in 30/99 (30%) TheraP participants assigned to LuPSMA and 30/101 (30%) participants assigned to cabazitaxel. The PSA50 RR in these men was 17/30 (57%) for LuPSMA versus 6/30 (20%) for cabazitaxel. In comparison, the PSA50 RR for men with MTV <200 mL on FDG PET was 48/69 (70%) for LuPSMA versus 31/71 (44%) for cabazitaxel. After accounting for treatment, the odds of a PSA50 response was lower among men with high MTV (OR 0.44; P=0.01).

Based on these results, Prof. Hofman concluded that in men with mCRPC, PSMA SUVmean ≥10 was predictive of a higher likelihood of favourable response to LuPSMA than cabazitaxel, and a high volume of disease on FDG PET was associated with a worse prognosis regardless of assigned treatment.

1. Hofman MS et al. Lancet 2021;397:797-804.
2. Buteau JP, et al. PSMA PET and FDG PET as predictors of response and prognosis in a randomized phase 2 trial of ¹⁷⁷Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic, castration-resistant prostate cancer (mCRPC) progressing after docetaxel (TheraP ANZUP 1603). Abstract 10, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April 202217 May 2024