Both Pluvicto (177LuPSMA-617) and Xtandi (enzalutamide) have been separately shown to delay progression and extend survival among metastatic and castration-resistant men with prostate cancer (mCRPC). Because they inhibit prostate cancer in different ways, it was hoped that combining them would have an additive benefit. In a clinical trial, enzalutamide temporarily increased expression of PSMA, so a synergistic effect is possible.
Emmett et al. reported the first results of the ENZA-p trial. 162 mCRPC patients with 2 or more risk factors were treated at 15 hospitals in Australia. Unlike the VISION trial, they did not previously receive docetaxel or 2nd line hormonal treatment for mCRPC. The risk factors were:
- metastatic at original diagnosis
- elevated LDH, ALP, albumin (PSA> 5 ng/ml)
- PSADT< 84 days
- < 3 years since diagnosis
- ≥5 bone or visceral metastases
- pain requiring opiates
- received abiraterone for mHSPC (docetaxel for mHSPC was allowed)
After 20 months of follow-up, the outcomes were:
- Median PSA Progression-Free Survival was 13.0 months for the combo vs 7.8 months for enza-only
- Median Radiographic Progression-Free Survival was 16 months for the combo vs 12 months for enza-only
- Percent with >50% PSA reduction was 93% for the combo vs 68% for enza-only
- Percent with >90% PSA reduction was 78% for the combo vs 37% for enza-only
- Too early for overall survival
- Improvement in pain scores were 61% for the combo vs 27% for enza-only
- Side effects for the combo vs enza-only were fatigue (75% vs 70%), nausea (47% vs 27%), and dry mouth (40% vs 10%).
- 81% received all 4 doses of Pluvicto.
Based on these results, and pending later follow-up on overall survival, Pluvicto should be combined with enza.
