Lutetium Lu 177 vipivotide tetraxetan showed a median overall survival of 13.1 months in the French PSMA-REACH mCRPC cohort.
Real-world outcomes with lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) were consistent with those reported in the pivotal phase 3 VISION trial (NCT03511664), with no new safety signals identified, according to findings from the retrospective French PSMA-REACH study (CAAA617A1FR03) presented at the
In the primary analysis population (n = 439), at a median follow-up of 6.8 months (95% CI, 6.2-6.9), the median overall survival (OS) was 13.1 months (95% CI, 12.0-14.9), and the estimated OS rates at 6, 12, and 18 months were 77.9% (95% CI, 74.0%-81.8%), 55.6% (95% CI, 50.9%-60.2%), and 39.4% (95% CI, 34.8%-44.0%), respectively. Median imaging-based progression-free survival (PFS) was 5.2 months (95% CI, 4.9-6.4) among evaluable patients (n = 431).
“In routine clinical practice, [lutetium Lu 177 vipivotide tetraxetan] demonstrated clinically meaningful efficacy with no new safety signal in a heavily pretreated population,” Philippe Barthélémy, MD, PhD, a medical oncologist at Strasbourg University Hospital in France, and colleagues wrote in the poster.
The phase 3 VISION trial established the efficacy of lutetium Lu 177 vipivotide tetraxetan in PSMA-positive mCRPC previously treated with androgen receptor pathway inhibitors (ARPIs) and taxane chemotherapy.2 Findings from VISION
PSMA-REACH was designed to complement clinical trial evidence by describing survival, treatment delivery, and imaging practices in routine French care.1 The investigators noted that earlier French early-access data provided a broader view of treatment use but left a need for additional chart-based information on these outcomes.
PSMA-REACH was a national, multicenter, noninterventional retrospective chart-review study conducted at 26 French sites. Participating centers consisted of university hospitals (53.8%) and cancer centers (46.2%), and every prescribing physician specialized in nuclear medicine.
Investigators abstracted medical-record data for patients who began treatment with lutetium Lu 177 vipivotide tetraxetan through France’s early-access program between October 1, 2023, and February 29, 2024. All patients had received prior ARPI therapy and taxane chemotherapy.
Among 443 enrolled patients, 439 were included in the primary analysis; 4 patients lacked sufficient data for that analysis but were retained in the safety population.
The primary end point was OS. Surviving patients were censored at the latest date they were last contacted or confirmed to be alive. Key secondary objectives included imaging-based PFS, patient characteristics, and safety. Imaging-based PFS spanned the interval from the start of therapy to death or the first progression seen on imaging, as judged by the investigator and documented in the chart. Both PET and conventional imaging were used. Of 1446 imaging examinations performed for tumor evaluation over the course of treatment, 605 were PET scans. The study also described time to treatment failure, best response, treatment patterns, and subsequent therapy.
The median age in the primary analysis population was 73.0 years (range, 37.0-90.0). Among patients with available Gleason scores (n = 400) 59.0% had scores of 8 to 10, and 41.0% had scores of 6 or 7. Of patients with known metastatic status at diagnosis (n = 432), 53.0% had metastatic disease at presentation.
Bone metastases were present in 93.2% of patients, and lymph node metastases were reported in 57.6%. Other metastatic sites included the liver (8.9%), lung (8.7%), and brain (0.9%); patients could have involvement at multiple sites.
The median number of prior treatments was 3. Patients had received a median of 2 ARPIs and 1 taxane chemotherapy; 209 patients (47.6%) had received at least 2 prior taxane chemotherapies.
Among patients with documented ECOG performance status (n = 421), 77.7% had a score of 0 or 1 and 84 (20.0%) had a score of 2. Nine patients had a score of 3 and 1 had a score of 4.
Median baseline prostate-specific antigen level was 64.5 ng/mL. Among patients with assessable creatinine clearance (n = 386), the median was 55.8 mL/min (range, 10.4-151.8). Creatinine clearance was below 30 mL/min in 6.2% of patients, 30 to less than 60 mL/min in 53.4% of patients, and at least 60 mL/min in 40.4% of patients. Ongoing comorbidities assessed using the Charlson score were reported in 34.4% of the overall population.
A total of 267 patients (60.8%) had died at the time of the OS analysis. In exploratory subgroup analyses, median OS was 15.8 months among patients with 1 prior taxane chemotherapy (n = 230) compared with 11.3 months among the patients who received at least 2 prior taxane chemotherapies (n = 209).
Median time to treatment failure was 8.7 months (95% CI, 7.9-9.3) among 434 patients.
Response data were missing for 70 patients. Among patients with response information (n = 369), the complete response rate was 5.1%, the partial response rate was 36.0%, the stable disease rate was 21.1%, and the progressive disease rate was 37.7%. Median times to complete and partial response were 5.0 and 4.6 months, respectively.
Patients received a median of 4 cycles. Overall, 39.6% received all 6 planned cycles, and 59.2% stopped treatment before the sixth cycle. Adverse effects (AEs) led to permanent discontinuation in 6.1% of patients, and 8.7% required at least 1 dose reduction.
In the safety population (n = 443), 15.8% experienced at least 1 prespecified AE during treatment. These AEs occurred a median of 3.1 months after treatment initiation, and 90.4% had resolved by the end of the study.
Subsequent therapy was reported for 195 patients (44.4%). Among these patients, cabazitaxel was the most frequently recorded next treatment at 46.2%, followed by enzalutamide (Xtandi) at 11.3%. Other reported options included radium-223 dichloride (Xofigo), olaparib (Lynparza), docetaxel, actinium-based PSMA therapy, and immunotherapy.
