Speaker
Prof.
Mike Sathekge
(University of Pretoria)
Description
Purpose: 225Ac- Prostate-specific membrane antigen (PSMA)-617 is a highly promising novel compound for therapy of prostate cancer. A remarkable therapeutic efficacy has been demonstrated in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients, with xerostomia as the main side effect. A promising strategy for minimization of side effects is based on optimization of the dosing regime while maintaining sufficient therapeutic efficacy for several cohorts of patients, including chemotherapy-naïve patients.
Subjects & Methods: Fifty-seven patients with progressive advanced prostate cancer that had exploited established first-line or second line therapies available in South Africa or that were not eligible or refused certain established therapies were selected for treatment with 225Ac-PSMA-617 on the basis of compassionate use. Therapy was performed in 2 months intervals, with initial dose of 8 MBq (or 10 MBq in case of very advanced disease, superscan), then de-escalation to 6 or 4 MBq in case of good response. The patients were divided into two groups: A: patients that have undergone standard therapy (surgery, radiation therapy and androgen deprivation) and some second line therapies (N=17). B: patients that have undergone only standard therapy or only parts (N=40), while some patients were completely treatment naïve (n=10). Prostate-specific antigen (PSA) and blood cell count were measured every 4 weeks. Monitoring and follow-up included Eastern Cooperative Oncology Group score, pain symptoms, treatment-related toxicity, PSA-response and ALP-response. 68Ga-PSMA-PET/CT was used for baseline staging and imaging follow-up every 8weeks.
Results: Good antitumor activity by means of objective radiologic response or tumor marker decline was observed in 71% of patients in group A while a remarkable 92% response rate was observed in group B. Chemotherapy-naïve patients exhibited significantly increased rate of response, and of complete response. Both groups presented with significant palliation of bone pain and reduced toxicity to salivary glands due to de-escalation. These interim results also show a favourable hematological and renal toxicity profile and quality of life improvements.
Conclusion: The remarkable therapeutic efficacy of 225Ac-PSMA617 reported earlier is confirmed with even better clinical outcomes in chemotherapy-naive advanced prostate cancer patients treated. Reduced toxicity to salivary glands due to de-escalation should be further explored for informing clinical practice and clinical trial design.
| Email Address | mike.sathekge@up.ac.za |
|---|---|
| Presentation Type | Contributed Oral |
Primary author
Prof.
Mike Sathekge
(University of Pretoria)
Co-authors
Prof.
Alfred Morgernstern
(EC, JRC, University of Pretoria)
Dr
Florette Reyneke
(University of Pretoria)
Dr
Frank Bruchertseifer
(EC, JRC)
Dr
Ismaheel Lawal
(University of Pretoria)
Dr
Kgomotso Mokoala
(University of Pretoria)
Prof.
Mariza Vorster
(University of Pretoria)
Dr
Otto Knoesen
(NTP)
Dr
Tebatso Boshomane
(University of Pretoria)
Dr
Thabo Lengana
(University of Pretoria)
