Using Lutetium-177 (Lu-177) After Limited Docetaxel Treatment in mCRPC

Evidence Supporting Lu-177 After Limited Docetaxel

The National Comprehensive Cancer Network (NCCN) guidelines recommend Lu-177-PSMA therapy for patients with metastatic castration-resistant prostate cancer (mCRPC) who have received limited docetaxel treatment, especially if they have PSMA-positive disease confirmed by imaging 1
The NCCN guidelines specifically highlight the TheraP trial, which demonstrated that Lu-177-PSMA-617 achieved a significantly higher PSA response rate (66%) compared to cabazitaxel (37%) in patients who had previously received docetaxel, regardless of the number of cycles 1
Lu-177-PSMA therapy has shown efficacy in patients who have progressed after taxane-based chemotherapy, with fewer grade 3-4 adverse events (33%) compared to alternative treatments like cabazitaxel (53%) 1

Patients should have confirmed metastatic castration-resistant prostate cancer 2
Patients should have limited response or progression after docetaxel treatment 1

Confirm mCRPC diagnosis and progression after limited docetaxel treatment 2
Assess patient's performance status and organ function 1
Monitor response after each cycle with PSA measurements and imaging as appropriate 1

Standard Lu-177-PSMA therapy typically consists of 3-5 cycles administered at 6-12 week intervals, with each cycle delivering 5.55-7.4 GBq (150-200 mCi) of radioactivity to PSMA-expressing tumor cells 3
The European Association of Nuclear Medicine recommends 4-6 cycles of Lu-177-PSMA treatment at 6-week intervals for metastatic castration-resistant prostate cancer (mCRPC), as established by the VISION trial 4

Continuing Lu-177 therapy beyond two cycles is reasonable and recommended for patients who have not progressed, even if lesions have not yet shown significant reduction, according to the European Society for Medical Oncology 4, 3
Regular monitoring of hematologic parameters is essential as myelosuppression can be cumulative with additional cycles, with common side effects including fatigue, dry mouth, nausea, and potential for thrombocytopenia, anemia, and lymphopenia 5

Patients with PSMA-expressing tumors without PSMA non-expressing lesions on PET-PSMA imaging should be considered for Pluvicto treatment, as demonstrated in a study published in Annals of Oncology 6
The European Society for Medical Oncology (ESMO) guidelines recommend 177Lu-PSMA-617 for patients with mCRPC who have received a novel androgen receptor axis inhibitor and docetaxel, with an ESMO-MCBS v1.1 score of 4 6, 7

The VISION trial demonstrated that Pluvicto plus best standard of care significantly improved overall survival (15.3 vs 11.3 months; HR 0.62, 95% CI 0.52-0.74, P<0.001) and radiographic progression-free survival (8.7 vs 3.4 months; HR 0.40, 99.2% CI 0.29-0.57, P<0.001), as reported in Annals of Oncology 6
Blood counts, renal, and hepatic function should be checked before each treatment cycle, and radioprotection precautions must be followed according to national and local regulations, as recommended in the Journal of Clinical Oncology 8
Multidisciplinary collaboration is recommended for optimal utilization of Pluvicto, as stated in the Journal of Clinical Oncology 8

The European Society for Medical Oncology (ESMO) recommends confirming PSMA-positive disease on PET imaging (68Ga-PSMA-11 or equivalent) with no PSMA non-expressing lesions, prior treatment with at least one androgen receptor pathway inhibitor, and prior treatment with docetaxel chemotherapy before initiating Lu-177-PSMA-617 therapy in patients with metastatic castration-resistant prostate cancer 9

The European Society for Medical Oncology (ESMO) assigns Lu-177-PSMA-617 the highest benefit score (ESMO-MCBS v1.1 score: 4) for mCRPC patients with PSMA-expressing tumors who have received prior androgen receptor axis inhibitor and docetaxel 9

The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) recommends using time-to-event endpoints, such as overall survival and radiographic progression-free survival, as primary measures in mCRPC trials, and also emphasizes the importance of serial biologic profiling to identify resistance mechanisms and distinguishing progression in existing lesions from new lesions 10, 11
The PCWG3 guidelines also suggest using the concept of "no longer clinically benefiting" to guide treatment discontinuation, which is aligned with the VISION trial design 10, 12, 11

The European Society for Medical Oncology (ESMO) acknowledges the theranostic approach of Pluvicto, which uses PSMA-targeted ligands linked to therapeutic radiopharmaceuticals, as a novel treatment option for mCRPC, and notes that it represents a distinct approach compared to other radiopharmaceuticals like radium-223 13
The National Comprehensive Cancer Network (NCCN) recommends considering Pluvicto as a treatment option for patients with PSMA-positive mCRPC who have progressed on AR pathway inhibitors and taxane chemotherapy, and notes that it is positioned after progression on these therapies 13