A recent study titled “Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial”, published in The Lancet Oncology journal, has concluded that radium-223 dichloride (Xofigo), a radiopharmaceutical drug for prostate cancer treatment, is effective independently of previous chemotherapy treatment.
After promising results from the ALSYMCA trial, Ra223 was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
Now, the same researchers who conducted the previous trial designed a prespecified subgroup analysis from ALSYMPCA in order to understand the effect of previous docetaxel use on the efficacy and safety of radium-223.
Robert B. Den, MD, and W. Kevin Kelly, DO, from the Departments of Radiation and Medical Oncology, at Thomas Jefferson University in Philadelphia, wrote an accompanying comment in the same journal edition, where they stated that “men who have received previous docetaxel chemotherapy can be given radium-223 safely and its efficacy will be similar to patients who have not received previous docetaxel treatment. The oncology community needs to proceed cautiously, since the ALSYMPCA trial was not able to identify the optimum sequence of administration of docetaxel and radium-233. Additionally, the trial was designed before the approval of enzalutamide and abiraterone acetate, so the clinical benefit of concomitant or sequential use of radium-223 with these drugs is unknown. Perhaps most intriguing would be the opportunity to integrate immunotherapy.”
In this phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, who had at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care, received either six injections of radium-223 or placebo for a month. Subjects had received previous docetaxel treatment or were unsuitable for or declined docetaxel.
The analysis showed that 57% of patients had received previous docetaxel treatment while 43% had not. Importantly, radium-223 was able to increase median overall survival when compared with placebo, independently of previous docetaxel use.
Furthermore, 62% of patients who had previously been treated with docetaxel had grade 3/4 adverse side effect, when compared with 54% of patients without docetaxel.
“Extensive use of previous docetaxel treatment (e.g., more than 6 cycles) might contribute to adverse effects with radium-223; however, this possibility cannot be investigated, since cumulative docetaxel dosing data were not collected in this trial”, the authors stated in their study.
Currently, a Phase 1/2 clinical study is ongoing to assess the efficacy of docetaxel and radium-223 in patients suffering from mCRPC who have developed bone metastases.
Additionally, the ERA 223 trial is currently enrolling patients with mCRPC and bone metastases to evaluate the efficacy of radium-223 and abirateron, a prodrug used in the treatment of mCRPC.
The results from this study highlight the current need to choose the most appropriate treatment for a particular patient. Factors that need to be taken into account by clinicians include patient comorbidities, the extent of the cancer, previous treatments, and the patient’s long-term goals of care.