Second line chemotherapy and visceral metastases are associated with poor survival in patients with mCRPC receiving 177Lu-PSMA-617

Abstract

The purpose of this study was to identify previous treatments and biomarker profile features that prognosticate overall survival (OS) in patients with mCRPC receiving ¹⁷⁷Lu-PSMA-617. Methods: 109 mCRPC patients treated with a median of 3 cycles of ¹⁷⁷Lu-PSMA-617 were included. Data were analyzed according to OS as well as PSA response patterns with regard to prior therapies, laboratory biomarkers and metastatic extent in univariate as well as multivariate Cox's proportional hazards models. PSA decline was assessed using the lowest PSA levels after the first cycle of therapy (initial PSA response) and during the entire observation period (best PSA response). Results: In total, 54 patients (49.5%) died during the observation period. First and second line chemotherapy were performed in 85% and 26%, and Abiraterone and Enzalutamide were administered in 83% and 85%, respectively. Any initial PSA decline occurred in 55% while 25% showed a PSA decline of ≥50%. The median estimated OS was 9.9 months (95% CI: 7.2-12.5) for all patients. Any initial decline of PSA was associated with significantly prolonged OS (15.5 vs. 5.7 months, p = 0.002). Second line cabazitaxel chemotherapy (6.7 vs. 15.7 months, p = 0.002) and presence of visceral metastases (5.9 vs. 16.4 months, p<0.001) were associated with shorter OS. Only visceral metastases remained significant in a multivariate analysis. Conclusion:¹⁷⁷Lu-PSMA-617 is an effective therapy for patients with mCRPC. However, the present data indicate that its beneficial effects on OS are strongly influenced by pretreatment (history of second line chemotherapy with cabazitaxel) and the presence of visceral metastases at onset of ¹⁷⁷Lu-PSMA-617 treatment.

Keywords: 177Lu-PSMA-617; PSMA; cabazitaxel; mCRPC; metastases; prostate cancer; radioligand therapy; second line chemotherapy.

Figure 1

A) Kaplan-Meier plot of overall survival (OS) of the entire cohort. B) Waterfall plot of the percental PSA response distribution among all patients with a measurable PSA response. Response values, known critical for OS are indicated as threshold (dotted lines at 30, 50 and 90 %). Asterisks indicate values higher than 100 % PSA increase. Kaplan-Meier plots of overall survival of patients presenting a best PSA decline of ≥30% (C) and ≥50 %. (D). CI=confidence interval, PSA = prostate specific antigen

Figure 2

A) Kaplan-Meier plots of overall survival of patients who had or had not received Cabazitaxel treatment. Comparison of cabazitaxel treated patients vs. untreated. Kaplan-Meier curves for visceral metastases is shown in (B)The distribution of metastases among CABA-treated patinets is shown in a stacked column graph in %, result of Chi²-test for the distribution of visceral metastases between CABA and no CABA is indicated with asterisks***p<0.001 (C) Kaplan-Meier plots are shown for OS between patints with or without liver (D) and lung (E) metastases including log rank test results. CABA = Cabazitaxel; OS=overall survival; CI=confidence interval; LN = lymph node, visMet = visceral metastases, VM=visceral metastases.

Figure 3

Dot plot comparisons are shown for certain parameters between four subgroups regarding liver metastases and cabazitaxel treatment including medians and standard deviation (A_E). Significant results are indicated by asterisks: *=p<0.01, **=p<0.001, ***=p<0.0001, ****=p<0.00001. PSA =prostate-specific antigen; LDH = lactate dehydrogenase; ALP = alkaline phosphatase; LM = liver metastases; CABA = cabazitaxel-treated