Abstract
Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (177Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative 177Lu-DOTAGA-(I-y)fk(Sub-KuE) (177Lu-PSMA I&T) with respect to efficacy and haematologic safety. Methods: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed. Results: One hundred patients completed one cycle of 177Lu PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50–89), median number of prior therapies was three (1–6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months (p < 0.0001; 95% CI: 0.08–0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated. Conclusion: 177Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. 68Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.
Highlights
Prostate cancer is the second most common cancer diagnosis in men and the fifth leading cause of death worldwide [1]
Following on from the success of first-generation anti-androgen therapies, numerous studies have demonstrated the efficacy of second-generation agents, including abiraterone [2,3], enzalutamide [4,5], and apalutamide [6], as single agents and in combination with other modalities [7] for metastatic castration-resistant prostate cancer
For chemotherapy), 177 Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) was associated with a higher incidence of grade ≥ 3 haematologic toxicity and overall grade 5 adverse events [9], substantiating previously reported concern for haematologic toxicity in heavily pre-treated patients [10,11]
Summary
Prostate cancer is the second most common cancer diagnosis in men and the fifth leading cause of death worldwide [1]. Androgen deprivation therapy (ADT), either surgical or chemical, remains the mainstay of initial therapy. Following on from the success of first-generation anti-androgen therapies, numerous studies have demonstrated the efficacy of second-generation agents, including abiraterone [2,3], enzalutamide [4,5], and apalutamide [6], as single agents and in combination with other modalities [7] for metastatic castration-resistant prostate cancer (mCRPC). Despite the demonstrated efficacy of antiandrogen-based salvage, the vast majority of patients will become resistant to ADT, developing advanced mCRPC. The limited overall efficacy of salvage chemotherapy and the associated burden on patients and health systems limits its utility. There remains an urgent unmet need for a safe, tolerable, and cost-effective non-chemotherapy-based approach for advanced mCRPC
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