Pluvicto vs ARPI in Prostate Cancer: Is One Better?

TOPLINE: 

Patients with metastatic castration-resistant prostate cancer who received Lu-177-PSMA-617 (Pluvicto) achieved similar overall survival and had fewer serious adverse events compared to those who switched androgen receptor pathway inhibitors (ARPI) after progressing on a first-line ARPI. However, the authors noted, the overall survival results “were likely confounded by the high rate of crossover” from a second-line ARPI to Lu-177-PSMA-617.

METHODOLOGY:

• Patients with metastatic castration-resistant prostate cancer who progress on first-line ARPI therapy and are taxane-naive may receive an ARPI in the second-line setting if they are unable to tolerate taxane-based chemotherapy. However, an ARPI is not the most active treatment in this setting.
• In the PSMAfore trial , researchers compared the efficacy of another agent — Lu-177-PSMA-617 — to an ARPI as a second-line treatment option. Overall, 468 patients with PSMA-positive metastatic castration-resistant prostate cancer were randomly assigned to receive either Lu-177-PSMA-617 (n = 234) or ARPI switch (n = 234). Participants had previously experienced disease progression on an ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide) and were deemed appropriate to delay taxane-based chemotherapy.
• Participants received Lu-177-PSMA-617 at a dose of 7.4 GBq once every 6 weeks for six cycles or ARPI change (abiraterone or enzalutamide at the treating physician’s discretion). Patients in the ARPI arm could cross over to Lu-177-PSMA-617 after centrally confirmed radiographic progression.
• In the initial analysis, radiographic progression-free survival appeared longer in patients receiving Lu-177-PSMA-617 compared to a second-line ARPI. During the final analysis , 60.3% of participants (141 of 234) randomly assigned to the ARPI switch group crossed over to receive Lu-177-PSMA-617, representing 75.4% of patients with confirmed radiographic progression.
• The median duration of exposure was 8.41 months in the Lu-177-PSMA-617 arm, 6.54 months in the ARPI-change arm, and 7.16 months in the crossover group.

TAKEAWAY:

• Median overall survival was similar in both groups: 24.48 months with Lu-177-PSMA-617 vs 23.13 months with ARPI change (hazard ratio [HR], 0.91; P = .20), according to the intention-to-treat analysis.
• In a crossover-adjusted analysis, patients receiving Lu-177-PSMA-617 demonstrated a significant survival benefit (HR, 0.59), which “suggested that treatment crossover likely confounded [overall survival],” the authors wrote.
• Treatment-emergent adverse events of grade 3 or higher were lower in the Lu-177-PSMA-617 group, as were rates of serious adverse events of any grade.
• In the Lu-177-PSMA-617 arm, more common adverse events included dry mouth and anemia. Dry mouth of any grade occurred in nearly 60% of participants, with less than 1% experiencing events of grade 3 or higher. Anemia of any grade occurred in about 27% of patients, with 6.2% experiencing events of grade 3 or higher. These events were predominantly low grade and resolved or were resolving at the final analysis.

IN PRACTICE:

Taken together with the previous observations from PSMAfore, “these results further support 177Lu-PSMA-617 as an alternative treatment option to ARPI change” in this patient population, the authors wrote.

SOURCE:

The study, led by Karim Fizazi, PhD, Institut Gustave Roussy and Centre Oscar Lambret, Université Paris-Saclay in Villejuif, France, was published online in Annals of Oncology.

LIMITATIONS:

The high rate of crossover probably confounded the overall survival analysis. The study excluded patients with known genomic alterations, limiting generalizability. Additionally, the trial may have been underpowered to detect an overall survival difference between arms, a limitation further exacerbated by the high crossover rate.

DISCLOSURES:

This study was funded by Novartis. Four authors reported being employees of and receiving restricted stock options from Novartis. Several authors reported receiving research grants or honoraria and having other ties with various sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.