Pluvicto (177Lu-PSMA-617) Is Not Yet Appropriate for This Patient
Your medical oncologist's recommendation to switch to Pluvicto is premature because this patient has not yet received taxane-based chemotherapy (docetaxel), which is required before Pluvicto according to FDA approval criteria and all major guidelines. 1, 2
Critical Missing Treatment: Docetaxel Chemotherapy
The next treatment step should be docetaxel chemotherapy, not Pluvicto. This patient has progressed on enzalutamide (an androgen receptor pathway inhibitor) but remains taxane-naïve, making docetaxel the guideline-recommended next step. 3
- Docetaxel every 3 weeks with prednisone provides a median overall survival of 16.3 months with an OS gain of 2.9 months (HR 0.79) and demonstrated improved quality of life in the TAX 327 trial. 1, 3
- Both ASCO and ESMO support moving to chemotherapy rather than sequential androgen receptor pathway inhibitors after ARPI failure, as demonstrated by the CARD trial showing superior outcomes with cabazitaxel versus switching ARPIs (median OS gain 2.6 months, HR 0.64). 1, 3
Why Pluvicto Requires Prior Taxane Therapy
FDA approval and the VISION trial specifically required patients to have received both androgen receptor pathway inhibition AND taxane-based chemotherapy before receiving Pluvicto. 1, 2
- The VISION trial enrolled only patients who had been treated with ≥1 androgen receptor pathway inhibitor AND one or two prior taxane-based chemotherapy regimens. 2
- ESMO assigns 177Lu-PSMA-617 a clinical benefit score of 4m (Form 2a) specifically for "adult patients with progressive PSMA-positive mCRPC who have been treated with androgen receptor pathway inhibition and taxane-based ChT." 1
- In the VISION trial, Pluvicto provided a median OS of 15.3 months versus 11.3 months (OS gain: 4.0 months; HR 0.62) in this heavily pretreated population. 1, 2
Treatment Algorithm for This Patient
Step 1: Initiate docetaxel chemotherapy now
- Administer docetaxel 75 mg/m² intravenously every 3 weeks with prednisone 5 mg orally twice daily. 3
- Continue ADT with LHRH agonist/antagonist to maintain castrate testosterone levels (<50 ng/dL) throughout treatment. 3, 4
Step 2: After docetaxel progression, obtain PSMA PET imaging
- PSMA expression on PET imaging is essential for determining 177Lu-PSMA-617 eligibility. 3, 4
- Only patients with PSMA-positive disease qualify for Pluvicto therapy. 1, 2
Step 3: If PSMA-positive after docetaxel failure, then consider Pluvicto
- Pluvicto 7.4 GBq (200 mCi) intravenously every 6 weeks for up to six doses becomes appropriate at this stage. 2
- Alternative option: cabazitaxel with prednisone/prednisolone (median OS 12.7 months, OS gain 2.4 months, HR 0.70 versus mitoxantrone). 1, 3
Essential Concurrent Actions
Perform comprehensive molecular testing now while initiating docetaxel:
- Test for BRCA1/2 mutations (germline and somatic) to identify candidates for PARP inhibitor therapy (olaparib, rucaparib) after docetaxel failure. 3, 5
- Olaparib provides median PFS gain of 3.8 months (HR 0.25-0.47) and OS benefit (HR 0.69) specifically in BRCA1/2-mutated patients after prior ARPI therapy. 1, 5
- Consider broader HRR gene panel testing (PALB2, RAD50, RAD51, BRIP1, ATM) for potential clinical trial enrollment. 5
Common Pitfall to Avoid
Do not skip docetaxel to go directly to Pluvicto. The recent PSMAfore trial (2024) demonstrated that 177Lu-PSMA-617 prolongs radiographic progression-free survival in taxane-naïve patients (median rPFS 11.60 months versus 5.59 months with ARPI change, HR 0.49), but this trial is not yet incorporated into FDA approval or standard guidelines. 6 Until regulatory approval expands, the standard sequence remains: ARPI → docetaxel → Pluvicto (if PSMA-positive). 1, 3, 2
Continue ADT indefinitely—never discontinue the LHRH agonist/antagonist even when adding chemotherapy or future Pluvicto therapy. 3, 4, 5