A prospective multicenter Swiss registry study (EKNZ 2021-01271) has demonstrated that 177Lu-PSMA-I&T, a radioligand therapy targeting prostate-specific membrane antigen (PSMA), is both safe and effective.
This first-of-its-kind study provides critical evidence supporting the use of ¹⁷⁷Lu-PSMA-I&T as a viable alternative to the established ¹⁷⁷Lu-PSMA-617 (Pluvicto), offering a promising option for patients with limited treatment choices after progressing on standard therapies.

The study enrolled 333 consecutive mCRPC patients who received a median of four cycles of ¹⁷⁷Lu-PSMA-I&T over 5.6 months, with a cumulative radiation dose of 24 GBq (ranging from 7 to 48 GBq). Patients had a median follow-up of 12 months and were heavily pre-treated, with 88% having received androgen receptor signaling inhibitors (ARSi) and 87% taxane-based chemotherapy. Most had high-risk disease (72% with Gleason score >8) and metastases in bones (94%), lymph nodes (71%), or visceral organs (26%). Safety was assessed through laboratory parameters and adverse events (AEs) graded per CTCAE v5.0, while efficacy was measured by PSA changes (using PCWG3 criteria and PSA90, a ≥90% PSA reduction), imaging responses (via SPECT/CT, CT, MRI, or PSMA PET-CT), and survival outcomes.

The therapy proved safe, with manageable side effects. Common treatment-related AEs included anemia (27%), thrombopenia (22%), leukopenia (15%), neutropenia (8%), and acute kidney injury (14%). Severe (grade 3–4) AEs were rare, affecting 8% for anemia, 3% for thrombopenia, 2% for leukopenia, and none for neutropenia or kidney injury. These findings align closely with the toxicity profile of ¹⁷⁷Lu-PSMA-617, suggesting comparable safety. Notably, the low rate of severe toxicities underscores ¹⁷⁷Lu-PSMA-I&T’s potential as a less toxic alternative to chemotherapy.
Efficacy results were encouraging. During treatment, 41% of patients achieved a partial PSA response (PR), and 27% had stable disease (SD), with 17% reaching a PSA90 response (≥90% PSA decline). At 12 weeks post-treatment, 26% maintained a PR, and 11% had SD. The median overall survival was 13 months (95% CI: 11.7–14.3), with a PSA progression-free survival (PFS) of 4.1 months (95% CI: 3.4–4.8) and imaging PFS of 6.5 months (95% CI: 5.4–7.6). These outcomes are comparable to those reported for 177Lu-PSMA-617 in phase III studies, reinforcing 177Lu-PSMA-I&T’s effectiveness in controlling tumor growth in heavily pre-treated patients.
While 177Lu-PSMA-617 remains the gold standard, approved by the FDA in 2022, the similar toxicity and efficacy profiles of 177Lu-PSMA-I&T suggest it could serve as an alternative, especially in settings where 177Lu-PSMA-617 is unavailable.

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