ESMO Pre-"Research" Newsletter Radioactive Ligand Therapy in mCRPC

The 2022 Annual Meeting of the European Society of Oncology (ESMO) was held

1392P-RALU study: Efficacy and safety assessment of mCRPC with ¹⁷⁷Lu-PSMA after ^{treatment with 233 Ra1}

background

Previous studies have confirmed that the use of ¹⁷⁷Lu-PSMA after ²³³Ra is acceptable

method

The investigators retrospectively collected patient data from the German Nuclear Medicine Center from 2021 to 2022 and according to the order of treatment (Ra-Ct-Lu: ²³³Ra was used first, followed by chemotherapy, and finally ¹⁷⁷Lu-PSMA; Ct-Ra-Lu: chemotherapy followed by ²³³Ra and ¹⁷⁷Lu-PSMA) to assess the efficacy and safety

outcome

A total of 133 patients were enrolled in the

73% of patients received 1-4 cycles of ¹⁷⁷Lu-PSMA, and 23% of patients received a cycle of ≥5

Figure 1 OS analysis of different treatment sequence groups

Table 1 Adverse event statistics

conclusion

In the real world, the use of ¹⁷⁷Lu-PSMA after ^{treatment with 233}Ra has acceptable safety and efficacy, and there is no cross-resistance
between the two.

The order of ²³³Ra and chemotherapy did not alter the safety and OS outcomes
of ¹⁷⁷Lu-PSMA.

1400P – SPLASH Study: ¹⁷⁷Lu-PNT2002 Efficacy and Safety Assessment of PSMA in ^mCRPC2

background

The SPLASH study was a Phase 3 study evaluating PSMA-targeted radioactive ligands that ^evaluatedthe efficacy and safety
of PSMA-positive mCRPC patients who progressed after receiving androgen-axis targeted therapy (ARAT) with 177 Lu-PNT2002 (¹⁷⁷Lu-PSMA-I&T).

method

This multinational, open-label study included 27 patients
prior to randomization.

Included patients were assessed for high expression of PSMA (PET/CT), no chemotherapy treatment for CRPC, progression after ARAT treatment, and bone marrow reserve and terminal
organ status.

Patients received 4 cycles of ¹⁷⁷Lu-PNT2002 (1 cycle every 8 weeks at a dose of 6.
8 GBq
).

The key endpoints of the study were progression-free survival (rPFS), overall survival, PSA response rate, dosimetry, and safety
as assessed by BUCR.

outcome

A total of 27 patients met the study inclusion criteria and 5 patients were excluded
.

Patients were treated with ¹⁷⁷Lu-PNT2002 for 4 cycles at a median dose of 6.
9 (6.
2-7.
5) GBq/cycle
.

Six patients (22%) had previously received paclitaxel for hormone sensitivity
.

At a median follow-up of 11.
7 months, the median OS was not yet reached and the median rPFS was 11.
5 months
.

The objective remission rate in imaging was 60%.

Figure 2 Kaplan-Meier analysis curve of rPFS

≥ grade 3 treatment adverse events (TEAEs) occurred in 8 patients, > 10% of patients developed anemia (3, 11.
1%) and hematuria (3, 11.
1%)
.

Treatment-related TEAEs with an incidence > 10% included dry mouth (7,25.
9%), nausea (5,18.
5%), fatigue (5,18.
5%), hematuria, and anemia (3,11.
1%)
.

conclusion

In patients with mCRPC who failed ALAT treatment, ¹⁷⁷Lu-PNT2002 was associated with better rPFS and was well
tolerated.

The PSA50 response rate showed a good anti-tumor effect
.

The above results support further research
on ¹⁷⁷Lu-PNT2002.

1414P - ¹⁷⁷Lu-PSMA efficacy and safety assessment in advanced patients with ^mCRPC3

background

¹⁷⁷ Lu-PSMA-RLT is a treatment option for patients with mCRPC and is increasingly used in elderly or comorbid patients
.

This study was designed to evaluate its efficacy and safety
in patients aged ≥ 80 years.

method

Between March 2016 and September 2021, a total of 79 patients with mCRPC received ¹⁷⁷Lu-PSMA-I&T-RLT, with a median age of 82 years (IQR: 81-84 years).


Patients have received androgen receptor-targeted therapy and paclitaxel-based chemotherapy, or have not met the chemotherapy conditions
.

All patients had high expression of PSMA ligands
on PSMA-PET examination.

Treatment consisted of 344 cycles (median cycle number 4, range: 1-12), median dose 27.
9 GBq (IQR: 14.
9-43.
9), with intervals of 4-6 weeks
.

Toxicity data were collected up to 6 months
after the end of the last treatment.

The study evaluated PSA response rates, PFS, and OS results
.

outcome

The median patient's previous mCRPC regimen was 2,50/79 (63.
3%) of patients who had not received chemotherapy prior to ¹⁷⁷Lu-PSMA treatment; Visceral metastases
were present in 14/79 patients (17.
7%).

PSA decreased by 90% in 25/79 patients (31.
6%) and 50% in 38/79 patients (48.
1%)
.

Patients who had not received chemotherapy had a higher response rate for PSA (a 50% decrease in PSA, 51.
0% vs 38.
.
7%)
compared to those who had received chemotherapy.

The median PFS and median OS of the overall patients were 8.
7 months and 16.
1 months
, respectively.

Median PFS and median OS were significantly better than those received chemotherapy (10.
5 months vs 6.
5 months, p=0.
015; 20.
7 months vs 11.
8 months, p<0.
01).
<b19>

Figure 3 Patient survival data analysis (a.
PSA-PFS； b.
Clinical PFS; c.
OS)

The most common grade 1- to 2 side effects are dry mouth, fatigue, and loss of appetite
.

Treatment-related grade 3 toxicity included anemia (4,5%), thrombocytopenia (3,4%), and chronic renal impairment (6,8%), and no non-hematologic grade 3 toxicity and any grade 4 toxicity were
observed.

conclusion

¹⁷⁷ The efficacy and safety of Lu-PSMA-RLT in elderly patients with mCRPC are consistent
with previous reports.

Patients who have not received chemotherapy respond better and last better to
treatment.

References

1.
K.
Rahbar, et al.
Lutetium-177-prostate-specific membrane antigen therapy (¹⁷⁷Lu-PSMA) in patients (Pts) with prior radium-223 (²²³ Ra): Safety and effectiveness outcomes.
2022 ESMO.
Abstract 1392P.

2.
A.
R.
Hansen, et al.
Efficacy and safety of ¹⁷⁷Lu-PNT2002 prostate-specific membrane antigen (PSMA) therapy in metastatic castration resistant prostate cancer (mCRPC): Initial results from SPLASH.
2022 ESMO.
Abstract 1400P.

3.
R.
L.
Tauber, et al.
Treatment efficacy and safety of ¹⁷⁷Lu-PSMA radioligand therapy in octogenarians with metastatic castration-resistant prostate cancer.
2022 ESMO.
Abstract 1414P.

Edit: LR Reviewer: LR Execution: LR