D. Schrijvers MD, PhD

BELFIGO – A retrospective observational study to evaluate the treatment patterns of mCRPC patients in Belgium treated with radium-223

SUMMARY

BELFIGO is a national retrospective chart review that aimed to assess the sequencing and application of radium-223 (Ra-223) within routine clinical practice, and evaluate the use of Ra-223 in monotherapy. The collection of data was primarily used to describe the proportion of Belgian metastatic Castration Resistant Prostate Cancer patients receiving one-four versus five-six Ra-223 injections, and the potentially associated patient characteristics. In total, 164 patients from eleven centres in Belgium were included and analysed in this study. Hundred-thirteen patients (69%) completed five-six injections of Ra-223. There was a trend that patients with a lower Eastern Cooperative Oncology Group Performance Status score, lower extent of disease on bone scan, alkaline phosphatase at baseline < 140 U/L and lactate dehydrogenase at baseline <250 U/L showed a higher chance of completing the six cycles of Ra-223. Median overall survival was estimated at 6.9 months for the patients having received one-four injections and 23.8 months for patients who completed five-six injections of Ra-223. More than 70% of patients received at least one treatment line after Ra-223, mainly enzalutamide, docetaxel or abiraterone acetate. These results show that the life-prolonging targeted alpha-therapy Ra-223 does not preclude the start of subsequent lines of treatment and that its use in an earlier line results, in a higher probability of reaching five-six doses. Patients with less advanced disease are more likely to complete five-six injections and tend to have a higher median overall survival.

(BELG J MED ONCOL 2020;14(7):347-54)

The hype of phase II trials

SUMMARY

Many of the new drugs are registered based on phase II data and surrogate endpoints. The medical oncologist should know the limitations and dangers of such an approach. The value of phase II trials and surrogate endpoints as well as clinical meaningful results are discussed.

(BELG J MED ONCOL 2019;13(7):273–6)

Appropriateness of treatment options in patients with metastatic castrationresistant prostate cancer with a focus on radium-223: outcomes of a Belgian multidisciplinary Consensus Meeting

SUMMARY

The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) has changed dramatically with the approval of a variety of therapeutic agents including abiraterone acetate, cabazitaxel, docetaxel, enzalutamide and radium-223 dichloride and the introduction of docetaxel and abiraterone acetate in combination with androgen deprivation therapy in newly diagnosed metastatic prostate cancer. Evidence on the optimal sequence of these therapies is scarce. In practice, the most appropriate treatment (sequence) depends on patient and disease characteristics. This article summarises the recommendations of a multidisciplinary group of Belgian experts in sequencing treatments for patients with mCRPC, with a focus on radium-223 dichloride.

(BELG J MED ONCOL 2019;13(6): 240–250)

Interventions in non-metastatic castration-resistant prostate cancer: earlier seems better

SUMMARY

Patients with non-metastatic castration-resistant prostate cancer benefit from an early treatment in terms of metastasis-free survival. Three drugs were compared with placebo in large randomised trials (SPARTAN, PROSPER, ARAMIS) and all showed an improvement in median metastasis-free survival. They differ in some of the secondary endpoints and side effects. This article discusses the results and the impact for patients with non-metastatic castration-resistant prostate cancer.

(BELG J MED ONCOL 2019;13(4):129–131)

Radium-223 in metastatic castration-resistant prostate cancer: a single centre experience

Radium-223 is one of the treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), based on the ALSYMPCA trail, a large randomised study.

In this retrospective study, the experience with radium-223 in patients with mCRPC, treated in a single centre, is reported in relation to the number of cycles of radium-223 given; reason of discontinuing radium-223 treatment, overall survival according to radium-223 treatments received; next treatment and interval to next treatment after discontinuing radium-223.

The Kaplan-Meier method was used to describe overall survival, and the log-rank was used to compare different groups.

Thirty-eight patients were analysed. A total of 26 patients (68.4%) completed all six cycles of radium-223, while twelve patients (31.6%) stopped treatment earlier. The reasons for discontinuing treatment early were progressive disease during treatment with radium-223 (four patients); myelotoxicity (one patient, who was previously treated for a small cell carcinoma of the ureter with six cycles of carboplatinum); intercurrent death due to non-prostate cancer-related diseases (four patients); patient refusal (one patient); complication due to co-morbid condition (one patient). And, one patient who stopped treatment after five cycles was lost to follow up.

Patients who completed all six cycles had a median survival time of 27.4 months (95% CI: 16.4-non applicable [NA; because the upper confidence limit never reaches the 50% survival]); and patients who completed one to four cycles 9.0 months (95% CI: 4.6-NA, log rank test: p<0.001).

Of the 26 patients who completed all six cycles, sixteen patients started another line of treatment for mCRPC after a median time of 30.0 weeks (95% CI: 18.1-NA) after the last injection of radium-223.

Radium-223 is an appropriate treatment for patients with mCRPC with a median overall survival of 27.4 months and a drug-free interval of 30 weeks after six cycles of radium-223.

(BELG J MED ONCOL 2019;13(1):16–20)

Treatment-induced anaemia in solid tumours with emphasis on newer anti-cancer drugs

Chemotherapy-induced anaemia is a well-known complication in cancer. With the venue of newer non-cytotoxic anti-cancer drugs, attention to anaemia and anaemia management has been shifted to the background. Nevertheless, anaemia is a frequent complication of some of these newer drugs. Mammalian target of rapamycin inhibitors, some of the antiangiogenic drugs, poly (ADP ribose) polymerases inhibitors and cyclin-dependent kinase inhibitors all can cause grade 3 or 4 anaemia. This review discusses the risks of anaemia development of anti-cancer drugs.

(BELG J MED ONCOL 2018;12(7):307–312)

Immuno-oncology in transitional cell Carcinoma

Immunotherapy has been used in the treatment of localised, high-risk transitional cell carcinoma. Bacillus of Calmette-Guérin therapy is a standard treatment for patients with non-invasive transitional cell carcinoma with bad prognostic factors (high-grade pTa; carcinoma in situ) and early stage invasive bladder cancer (pT1) after transurethral resection of the bladder. Recently, based on phase II trials, atezolizumab, an inhibitor of PD-L1, and nivolumab, an inhibitor of PD1, have been registered for the treatment of patients with metastatic transitional cell carcinoma progressing after a platinum-based chemotherapy for metastatic disease. Pembrolizumab, a monoclonal antibody against programmed death receptor-1 was registered based on a phase III trial in this setting resulting in a survival benefit compared to second-line chemotherapy. Predictive markers are being explored for a better patient selection for the treatment of transitional cell carcinoma.

(BELG J MED ONCOL 2018;12(5):218–222)