Leading the new era of precision: Pluvicto, the first radioligand therapy in the mCRPC field, was approved by the FDA!

On March 23, 2022, Pluvicto (lutetium Lu 177 vipivotide tetraxetan, 177Lu-PSMA-617) was approved by the FDA for the treatment of prostate-specific membrane antigen (PSMA)-positive patients who have received an androgen receptor (AR) inhibitor and taxane-based chemotherapy in adult patients with metastatic castration-resistant prostate cancer (mCRPC)
.

 On the same day, the FDA approved Locametz (gallium Ga 68 gozetotide), a radiodiagnostic agent for positron emission tomography (PET) of PSMA-positive lesions, to select patients with metastatic prostate cancer who can be treated with Pluvicto
.

Locametz is the first radiodiagnostic agent approved for selective radioligand therapy
.

 Patients with previously treated mCRPC should be selected using Locametz or another approved PSMA-11 imaging agent based on tumor PSMA expression
.

PSMA is highly expressed in more than 80% of prostate cancers
.

177Lu-PSMA-617 is a radioligand therapy targeting PSMA
.

It consists of a targeting compound (ligand) combined with a therapeutic radioisotope that binds to PSMA-expressing prostate cancer cells, and subsequent release of the radioisotope will damage the tumor cells, disrupt their ability to replicate, and trigger tumor cell death
.

177Lu-PSMA-617 Targeted Radioligand Therapy Mechanism Model This approval is based on the results of the Phase III VISION study
.

At this year's ASCO conference, the VISION study announced its findings in the form of an LBA abstract
.

This study is the first to demonstrate that a PSMA-targeted radioligand therapy (177Lu-PSMA-617) can significantly improve mCRPC survival, adding a novel radionuclide therapy to advanced prostate cancer after Ra-223
.

VISION is an international, open-label, multicenter Phase III clinical study to evaluate the best standard of care (SOC) (n=551) versus SOC (n=280) selected by the 177Lu-PSMA-617 co-investigator Efficacy and safety for PSMA-positive mCRPC
.

All patients received GnRH analog therapy or had prior bilateral orchiectomy
.

Enrolled patients received at least one AR inhibitor and one or two taxane-based chemotherapy regimens
.

Patients received 177Lu-PSMA-617 treatment every 6 weeks + SOC (7.
4 GBq, 200 mCi, up to 6 doses) or SOC only
.

The primary endpoint was radiographic progression-free survival (rPFS)
.

At a median follow-up of 20.
9 months, the 177Lu-PSMA-617+SOC group had a 60% reduction in the risk of radiographic progression or death compared with the SOC group, and the median rPFS of the 177Lu-PSMA-617+SOC and SOC groups were 8.
7 months and 3.
4 months (HR=0.
40, 99.
2%CI: 0.
29-0.
57; P<0.
001)
.

rPFS results The median overall survival of the two groups was 15.
3 months and 11.
3 months, respectively, and the risk of death was reduced by 38% (HR=0.
62, 95%CI: 0.
52-0.
74; P<0.
001)
.

OS results In addition, ORR (29.
8% vs 1.
7%), DCR (89.
0% vs 66.
7%), and time to first bone symptom (11.
5 vs 6.
8 months) were also improved
.

No unexpected adverse events and uncontrollable adverse events were found in the experimental group
.

Safety analysis VISION study showed that adding 177Lu-PSMA-617 to standard therapy improved PFS and OS in previously treated mCRPC patients and was well tolerated
.

The results support the combination regimen as a new treatment option for mCRPC patients
.

References: [1] https:// [2] Phase 3 study of 177Lu- PSMA-617 in patients with metastatic castration resistant prostate cancer (VISION).
LBA4.
2021 ASCO.
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