New multicenter prospective research suggests that the radioligand therapy (177Lu)Lu-PSMA-I&T may provide a viable treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC).
For the study, recently published in the Lancet Medical Imaging and Theranostics, researchers reviewed data in 333 men with mCRPC who were treated with (177Lu)Lu-PSMA-I&T. The median follow-up period was 12 months, according to the study. The study authors indicated that contrast-enhanced CT, MRI or PSMA PET/CT, or a combination of all three, were utilized to evaluate radiographic progression.
The researchers found that over 64 percent of patients demonstrated a decline in prostate-specific antigen (PSA) level. Over 44 percent of the cohort had a PSA50 response and 17.9 percent had a PSA90 response, according to the study authors.
While treatment discontinuation and dose reduction occurred in 5 percent and 7 percent of the cohort, respectively, due to treatment-related adverse events, the researchers noted no cases of grade 3 or worse renal toxicity. The study authors also noted generally mild xerostomia in 15 percent of the cohort.
“Overall, the deterioration in quality of life, represented by patient-reported xerostomia, pain, and quality-of-life measures, should be interpreted in the context of the clinically meaningful disease control and survival outcomes observed in this heavily pretreated population,” noted lead study author Alin Chirindel, MD, who is affiliated with the Division of Nuclear Medicine at the University Hospital of Basel in Basel, Switzerland, and colleagues.
The study authors cautioned that grade 3 lymphopenia occurred in 21.1 percent of the cohort. However, the researchers also found that there were no cases of treatment-related death or secondary malignancies with administration of (177Lu)Lu-PSMA-I&T.
Three Key Takeaways
• Meaningful efficacy in a heavily pretreated population. More than 64 percent of patients had a PSA decline, with a 44% PSA50 response rate and median overall survival of 13.2 months—supporting (177Lu)Lu-PSMA-I&T as a viable option for mCRPC patients who've already exhausted other lines of therapy.
• Favorable renal safety profile, but hematologic toxicity warrants monitoring. No grade 3+ renal toxicity and no treatment-related deaths or secondary malignancies were observed, though grade 3 lymphopenia occurred in 21.1 percent of patients.
• Tolerability trade-offs are modest relative to benefit. Treatment discontinuation (5 percent) and dose reduction (7 percent) were relatively uncommon, and xerostomia was generally mild (15 percent), supporting the authors' view that quality-of-life impacts should be weighed against the disease control and survival benefits seen in this population.
The study results with (177Lu)Lu-PSMA-I&T revealed median PSA progression-free survival of 4.8 months and median overall survival of 13.2 months, according to the authors.
“These findings provide prospective evidence supporting the safety and clinical activity of (177Lu)Lu-PSMA-I&T in routine management of mCRPC,” posited Chirindel and colleagues.
(Editor’s note: For related content, see “FDA Expands Approval of Pluvicto in Combination with ARPI for PSMA-Positive mAPMN/S Prostate Cancer,” “SNMMI: Does Vaccination Enhance Pluvicto Efficacy in mCRPC?” and “Early SPECT/CT Response After Pluvicto May Help Predict Survival in Patients with mCRPC?”)
In regard to study limitations, the authors acknowledged a lack of standardization with imaging modalities and quantitative response thresholds, and no systematic collection of dosimetry data. The researchers also acknowledged no conclusions with respect to comparative efficacy due to the study’s single-arm registry design.
