A large international clinical trial led in part by Weill Cornell Medicine found that adding a targeted radioactive drug earlier in treatment can significantly delay progression of metastatic prostate cancer.
The phase 3 PSMAddition trial showed that adding lutetium PSMA 617 vipivotide tetraxetan, also known as 177Lu-PSMA-617, to standard hormone-based therapy reduced the risk of disease progression seen on scans or death by 28% in patients with PSMA-positive metastatic prostate cancer.
The findings were published Aug. 6 in The Lancet and have already influenced treatment policy. The U.S. Food and Drug Administration approved earlier use of the drug in late July for patients with PSMA-positive metastatic prostate cancer.
About 90% of patients with metastatic prostate cancer have tumors that test positive for prostate-specific membrane antigen, or PSMA, according to Dr. Scott Tagawa of Weill Cornell Medicine, the study’s lead author.
Until now, the standard treatment backbone has generally involved an androgen receptor pathway inhibitor combined with androgen deprivation therapy.
The new trial tested whether adding 177Lu-PSMA-617 at diagnosis, rather than waiting until the cancer became resistant to initial treatment, could improve outcomes.
More than 1,100 patients at 169 sites in 20 countries participated in the study.
Half received 177Lu-PSMA-617 every six weeks along with androgen deprivation therapy and an androgen receptor pathway inhibitor. The other half received the previous standard two-drug treatment.
Patients in the control group were allowed to switch to the triple-therapy regimen if their cancer progressed.
Treatment delayed progression and resistance
Researchers found that patients receiving the three-drug combination had longer radiographic progression-free survival.
The treatment also delayed the point at which patients developed resistance and needed to move to another therapy.
Researchers also reported that the drug delayed symptoms associated with cancer spreading to the bones.
Earlier studies had shown 177Lu-PSMA-617 could benefit patients with treatment-resistant metastatic prostate cancer, leading to its approval for that use in 2022.
The new findings suggest many patients may no longer need to wait until their disease becomes resistant before receiving the therapy.
Drug targets prostate cancer cells with radiation
177Lu-PSMA-617 is a targeted radionuclide therapy.
The treatment combines a molecule that seeks out the PSMA protein on prostate cancer cells with a radioactive component.
That allows the drug to deliver radiation directly to cancer cells while relatively sparing surrounding normal tissue.
The approach is the result of more than two decades of research involving investigators at Weill Cornell Medicine, NewYork-Presbyterian and Memorial Sloan Kettering Cancer Center.
Side effects increased with triple therapy
The additional treatment also produced more adverse events, which researchers said was expected with a three-drug regimen.
Dry mouth was the most common side effect and occurred in 46% of patients receiving 177Lu-PSMA-617.
Fatigue was also common and is associated with both radiation and hormonal treatment.
Researchers are continuing to analyze longer-term outcomes, including overall survival and potential safety concerns associated with prolonged use.
Tagawa cautioned that the therapy will not necessarily be appropriate for every patient.
Specialized imaging is required to determine whether a tumor is PSMA-positive, and the drug can only be administered by nuclear medicine physicians or radiation oncologists.
That could create access problems for patients living far from academic medical centers or other facilities equipped to provide the treatment.
Radiotherapy patients must also follow precautions intended to limit radiation exposure to other members of their household.
More treatment options emerging
The study adds another option to a rapidly expanding group of targeted treatments for metastatic prostate cancer.
Researchers said newer imaging technology is allowing physicians to identify tumors that previously could not be detected and better match treatments to individual tumor characteristics.
Tagawa said several therapies now appear capable of delaying metastatic prostate cancer progression, though researchers are still determining whether those improvements ultimately translate into longer overall survival.
The PSMAddition trial was funded by Novartis. Tagawa serves as a paid consultant for the company.
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