Professional Statements and Societal Positions Guidelines
The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.
Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in 'Supplemental Information' if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.
National Comprehensive Cancer Network
The National Comprehensive Cancer Network guideline for prostate cancer (v1.2023 ) provides the following relevant recommendations with regard to the use of lutetium Lu 177 vipivotide tetraxetan (Lu-177-PSMA-617):
12,
'The NCCN Panel recommends Lu-177-PSMA-617 as a category 1, useful in certain circumstances treatment option for patients with ≥1 PSMA [prostate-specific membrane antigen]-positive lesion and/or metastatic disease that is predominately PSMA-positive and with no dominant PSMA-negative metastatic lesions who have been treated previously with androgen receptor-directed therapy and a taxane-based chemotherapy. PSMA-negative lesions are defined as metastatic disease that lacks PSMA uptake including bone with soft tissue components ≥1.0 cm, lymph nodes ≥2.5 cm in short axis, and solid organ metastases ≥1.0 cm in size. The NCCN Panel believes that both Ga-68 PSMA-11 or F-18 piflufolastat PSMA imaging can be used to determine eligibility.'
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 8.
Table 8. Summary of Key Trials
NCT No. | Trial Name | Planned Enrollment | Completion Date |
Ongoing |
NCT04720157
a | An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination with SoC, Versus SoC Alone, in Adult Male Patients with mHSPC (PSMAddition) | 1126 | Feb 2026 |
NCT04689828
a | 177Lu-PSMA-617 vs. Androgen Receptor-directed Therapy in the Treatment of Progressive Metastatic Castrate Resistant Prostate Cancer (PSMAfore) | 450 | Jan 2025 |
NCT04663997 | A Randomized Phase II Study of 177 LuPSMA-617 vs Docetaxel in Patients With Metastatic Castration-Resistant Prostate Cancer and PSMA-Positive Disease | 200 | Jul 2025 |
NCT05150236 | Phase II Study of Radionuclide 177Lu-PSMA Therapy Versus 177Lu-PSMA in Combination With Ipilimumab and Nivolumab for Men With Metastatic Castration Resistant Prostate Cancer (mCRPC) | 110 | Dec 2024 |
NCT: national clinical trial.
a
Denotes industry-sponsored or cosponsored trial.
Lutetium Lu 177 vipivotide tetraxetan
Lutetium Lu 177 vipivotide tetraxetan (Lu-177-PSMA-617) is a radiopharmaceutical and should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals.
The recommended dose of Lu-177-PSMA-617 (Pluvicto
TM
) is 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses.
Patients should be well-hydrated during treatment.
Refer to the prescribing information for Lu-177-PSMA-617 for recommended dosage modifications for adverse reactions. The management of adverse reactions may require temporary dose interruption (extending the dosing interval from every 6 weeks up to every 10 weeks), dose reduction, or permanent discontinuation of treatment with Lu-177-PSMA-617. The dose of Lu-177-PSMA-617 may be reduced by 20% to 5.9 GBq (160 mCi) once; the dose should not be re-escalated.
Lu-177-PSMA-617 should be discontinued permanently if the patient develops any of the following:
- Recurrent Grade 3 or higher myelosuppression after 1 dose reduction
- Grade 3 or higher renal toxicity
- Recurrent renal toxicity after 1 dose reduction
- Recurrent Grade 3 dry mouth after 1 dose reduction
- Recurrent Grade 3 or higher gastrointestinal toxicity after 1 dose reduction
- Aspartate aminotransferase or alanine aminotransferase greater than 5 times the upper limit of normal in the absence of liver metastases
- Any unacceptable toxicity
- Any serious adverse reaction that requires treatment delay of greater than 4 weeks
- Any recurrent Grade 3 or 4 or persistent and intolerable Grade 2 adverse reaction after 1 dose reduction
Table PG1 describes the grading of severity used in the Common Toxicity Criteria for Adverse Events (version 4.03).
Table PG1. Common Toxicity Criteria for Adverse Events, Version 4.03
Grade | Description |
1 | Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. |
2 | Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living and refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. |
3 | Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living and refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. |
4 | Life-threatening consequences; urgent intervention indicated. |
5 | Death related to adverse event. |
