PSA Levels at 8 Months Predict Survival Outcomes With ADT Combinations in mCRPC

Prostate-specific antigen (PSA) levels 8 months after the start of androgen deprivation therapy (ADT) in patients with de novo metastatic castration-sensitive prostate cancer (mCSPC) were a stronger predictor of both radiographic progression-free survival (rPFS) and overall survival (OS), according to a recent analysis of data from the phase 3 PEACE-1 study (NCT01957436).^1,2

Based on these results indicating less favorable outcomes in patients with PSA levels greater than 0.2 ng/mL regardless of treatment intervention, investigators led by Gwenaëlle Gravis Mescam, MD, concluded that early therapeutic interventions in this subgroup should be evaluated.

“[The] 8-month PSA value strongly predicts both rPFS and OS in men with mCSPC in PEACE-1,” investigators wrote. “Early therapeutic intervention in men with unfavorable 8-month PSA values needs to be investigated.”

This preplanned analysis found the median rPFS to be 4.0 years (95% CI, 3.6-not evaluable [NE]) in patients treated with ADT with or without docetaxel with an 8-month PSA value at or below 0.2 ng/mL, as compared with 1.4 years (95% CI, 1.2-1.7) in those with a PSA value greater than 0.2 ng/mL (P <.0001). The correlation also occurred in patients treated with the same regimen plus abiraterone acetate (Zytiga), for whom rPFS was NE (95% CI, 4.7-NE) in those with PSA levels at or below 0.2 ng/mL vs 2.2 years (95% CI, 1.6-2.9) in those with PSA above 0.2 ng/mL (P <.0001).

Patients treated with standard of care with a PSA level at or below 0.2 ng/mL had an OS that was NE (95% CI, 4.8-NE) vs 3.5 years (95% CI, 3.1-4.1) in those with levels higher than 0.2 ng/mL (P <.0001). The difference in outcomes was larger in patients treated with standard of care plus abiraterone. Those with PSA levels at or below 0.2 ng/mL had an OS that was NE (95% CI, 5.7-NE) vs 3.4 years (95% CI, 2.8-3.9) for those with levels greater than 0.2 ng/mL (P <.0001). The analysis also noted that patients treated with abiraterone were significantly more likely to have PSA levels of 0.2 ng/mL or lower at this timepoint.

PSA data were available for 931 out of the 1172 patients with de novo mCSPC enrolled in the open-label, randomized, phase 3 PEACE-1 study that was conducted in 7 countries across the European Union. Patients in the study were required to have histologically or cytologically confirmed metastatic disease, an ECOG performance status not greater than 1, and a life expectancy of at least 6 months to be included.²

The PEACE-1 study randomized patients 1:1:1:1 to 4 treatment regimens: standard of care (ADT with or without intravenous docetaxel at 75 mg/m² once every 3 weeks), standard of care plus radiotherapy, standard of care plus oral abiraterone at 1000 mg once daily plus oral prednisone at 5 mg twice daily, or standard of care plus abiraterone and radiotherapy. Data showed that patients assigned to receive abiraterone across treatment groups (n = 583) had longer rPFS (HR 0.54; 99.9% CI, 0.41-0.71, P < .0001) and OS (HR 0.82; 95.1% CI, 0.69-0.98; P = .030) than patients who did not receive abiraterone (n = 589).²

“The clinical and molecular characteristics of the population with elevated 8-month PSA values deserve better understanding,” investigators concluded.

These data were presented at the 2022 European Society for Medical Oncology (ESMO) Congress and support future research into the predictive power of PSA levels in patients with prostate cancer.

References

1. Gravis Mescam G, Maldonado X, Roubaud G, et al. 8-month PSA strongly predicts outcomes of men with metastatic castration-sensitive prostate cancer in the PEACE-1 phase III trial. Ann Oncol. 2022;33(suppl 7):1361MO. doi:10.1016/annonc/annonc1070
2. Fizazi K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022;399(10336):1695-1707. doi:10.1016/S0140-6736(22)00367-1