For Patients With mCRPC, Results With Pluvicto in Real-World Settings Keep Pace With Clinical Trials

When a new therapy hits the market, physicians in clinical practice know the drill: payers may put them through hoops for the first 6 months to a year, until the evidence from patients who weren’t on clinical trials starts to roll in.

That’s why the results presented February 26, 2026, by Daniel George, MD, the highly regarded medical oncologist from Duke University School of Medicine, are so impressive. The real-world data George shared at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in San Francisco on the radioligand therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto; Novartis) matched those of PSMAfore (NCT04689828).^1,2 This clinical trial supported FDA approval for patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC), who have been treated with androgen receptor pathway inhibitors (ARPIs) and who can delay taxane-based chemotherapy.³

George, a professor of medicine and surgery at Duke, presented findings from the PRECISION platform, a Novartis-developed real-world evidence database that integrates data from more than 56,500 patients with metastatic prostate cancer. The core finding of George’s analysis of data from 500 real-world patients was a median progression-free survival (PFS) of 13.5 months in chemotherapy-naive patients with PSMA-positive mCRPC who had received at least 1 ARPI (95% CI, 11.7-14.7 months).^1,2

In the PSMAfore pivotal trial, Pluvicto more than doubled median radiographic PFS compared with a change in ARPI—11.6 months vs 5.6 months.

“Let me just say this is unusual,” George explained in an interview with The American Journal of Managed Care^® (AJMC^®). “Typically, when we treat patients off protocol, we're taking patients that are much more diverse population, older, more comorbidities, more frailty, patients that may have more burden of disease—and maybe a little bit variable PSMA uptake on their PET scans than what we select for in our clinical trials. And yet, despite all of those potential variables, we're seeing equal results.”

He described radiographic progression-free survivals of “outwards of 1 year” being recapitulated in practice as “really fantastic for patients” and as validation of “the robustness of this therapy.”

One of the more actionable findings from the PRECISION data concerns treatment sequencing, George explained. Chemotherapy-naive patients who received Pluvicto after only 1 ARPI achieved a median PFS of 15.8 months (95% CI, 11.7-18.6 months), compared with 12.7 months (95% CI, 10.7-14.0 months) in those who had received multiple ARPIs before starting Pluvicto.^1,2

The PSA50 response rate—a measure of at least a 50% decline in prostate-specific antigen—was similar across both groups, at approximately 62%.^1,2

In a statement, George highlighted the clinical significance of the findings. “This analysis validates what many of us have seen in the clinic—that lutetium Lu 177 vipivotide tetraxetan can achieve clinically relevant responses across a diverse set of patients and in various practice settings. These results show reassuring consistency with the PSMAfore pivotal trial and should strengthen clinicians’ confidence in using radioligand therapy for patients after one ARPI.”²

So many of today’s questions in cancer care surround sequencing, and prostate cancer is no exception: the development of new treatments invites debate over which therapy to give first, second, and so on. Asked why the mechanism of the radioligand therapy works particularly well after 1 APRI treatment, George explained that the biology underlying this advantage is rooted in the nature of castration-resistant disease, which he said should now be more precisely termed androgen pathway modulation resistant, or APMR, disease.

Once prostate cancer progresses past the androgen receptor pathway, he explained, “We see that there's more nuance to the population.” Pluvicto's targeting of PSMA, which is expressed on the majority of these tumors, allows it to kill cancer cells regardless of that heterogeneous underlying biology. “By giving something like this that gets into those cells and kills them, indiscriminate of that genetic background, is really fantastic,” he said.

In addition, this ordering of therapy allows patients to delay chemotherapy, which George said represents a meaningful end point for patients, not just a regulatory or statistical one: “Once they go on to chemotherapy, it’s a double-edged sword. It may treat the cancer, but it really takes them down, and they might never have the time to rehabilitate from that.” He sees Pluvicto’s role in pushing chemotherapy further down the line as one of its most important attributes.

There is emerging evidence of Pluvicto’s value in earlier disease settings. When the radioligand therapy is added to ARPI therapy in hormone-sensitive disease, "we see an additive benefit to the Pluvicto dose.” A completed study is still maturing, he said, adding, “Could this drug work even better at delaying disease progression and complications by treating even earlier? That study is done, but we’ll see how that data matures.”

Safety and tolerability. George said real-world evidence provides fewer details than clinical trial data; instead of reporting on specific adverse events, he pointed to treatment completion as a proxy. "How many patients completed all 6 doses?”

He pointed to a “very high rate” of all patients completing all doses, which he said shows “that the drug is tolerable.” The median number of doses received was 4, with an IQR of 2 to 6.¹ Of note, he said no population subgroup has so far emerged as particularly resistant or intolerant, but more data are needed for patients with significant comorbidities such as renal or liver failure.

Access and awareness. Asked about patient access, George said the picture is mixed. At a major academic center like Duke, the infrastructure needed for delivery of Pluvicto is in place: nuclear medicine specialists, radiation oncologists, and a multidisciplinary team. He credited Novartis with running awareness campaigns and doing “a really fantastic job of opening up the availability of this agent around the country.” But if one ventures beyond his North Carolina campus, there are gaps.

“There are still parts of the country, particularly here in the Southeast where I live, in rural areas where there is no infrastructure for oncology,” he said. “For those patients, it's very difficult to access this drug. They would have to drive hundreds of miles in some cases, and they might not have the health literacy, the resources, the trust, and motivation to seek that out.”

George called for creative solutions, perhaps including mobile units that could reach underserved communities. “As we make progress, we need to also remember how to expose that to the greatest number of patients.”

References

1. George DJ, Heath EI, Shore, ND, et al. Real‑world outcomes of [177Lu]Lu‑PSMA‑617 in taxane‑naïve patients with metastatic castration‑resistant prostate cancer (mCRPC): a PRECISION data platform analysis. J Clin Oncol. 2026;44(suppl 7): abstr 81. doi:10.1200/JCO.2026.44.7_suppl.81
2. New real‑world data reinforce earlier use of Pluvicto before chemotherapy in metastatic castration-resistant prostate cancer. News release. Novartis. February 24, 2026. Accessed February 26, 2026. https://www.novartis.com/news/media-releases/new-real-world-data-reinforce-earlier-use-pluvictotm-chemotherapy-metastatic-castration-resistant-prostate-cancer
3. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. News release. FDA. March 28, 2025. Accessed March 3, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indicat