Beyond cabazitaxel: Late line treatments in metastatic castration resistant prostate cancer: A retrospective multicentre analysis

Abstract

Aims Multiple life‐prolonging therapies are available for metastatic castration‐resistant prostate cancer (mCRPC). However, the optimal treatment strategy following progression through standard treatment with docetaxel, androgen receptor signaling inhibitor (ARSI) and cabazitaxel, remains unclear. We aimed to describe treatment patterns in men with mCRPC following progression on standard treatments and determine whether subsequent treatment choice impacts overall survival. Methods Clinicopathologic and treatment data were extracted from the electronic CRPC Australian Database (ePAD) for patients who had received docetaxel, ARSIs and cabazitaxel in any order. Data were analyzed to compare groups that did versus did not receive subsequent systemic therapy. Treatment sequences, median duration of treatment, and median overall survival (mOS) were reported for each treatment group. Results Ninety‐eight eligible patients were identified, with 51 receiving subsequent systemic therapy. Those who received further treatment were younger (68 vs. 71 years, p < .01) but did not have any other differences in clinicopathologic features compared to those who received no further treatment. Patients who received upfront docetaxel were more likely to proceed to subsequent treatment (p = .02). Subsequent systemic therapies varied, the most common being carboplatin‐based regimens (n = 13, 25.5%) and many patients were rechallenged with ARSI (n = 10, 19.6%) or docetaxel (n = 6, 11.8%). There was no difference in mOS according to subsequent systemic therapy (p = .09). Conclusion This retrospective multicenter analysis demonstrates the variation in treatment sequences used for mCRPC in the real‐world setting. In the absence of high quality, prospective evidence, our results suggest that subsequent treatment choice does not influence survival outcomes and the optimal choice is guided by individual patient and disease‐related factors.

Survival beyond cabazitaxel for metastatic castration‐resistant prostate cancer

“…An Australian study found longer OS in patients who received subsequent treatment beyond cabazitaxel in patients who received ARSI, docetaxel, and cabazitaxel, than in those without further therapy after cabazitaxel. 2 Conversely, that study found no OS difference when comparing different treatment groups, probably by the different agents they used after cabazitaxel such as cyclophosphamide, or trials, that were not used in this study. Therefore, further research is required to know the role of each agent after cabazitaxel to prolong OS.…”

“…1 Little is known about survival in subsequent treatment beyond cabazitaxel. 2 Therefore, we described the treatment patterns in mCRPC beyond cabazitaxel and determined its impact on survival.…”

Treatment landscape and burden of disease in metastatic castration-resistant prostate cancer: systematic and structured literature reviews

“…The most frequent 1L-to-2L treatment sequence in a large retrospective study in the US was abiraterone-to-enzalutamide, followed by enzalutamide-to-abiraterone ( 82 ), while in Ontario, Canada, the preference was to provide a subsequent (2L) treatment with a different mechanism of action (abiraterone or enzalutamide followed by docetaxel, with Ra-223 being the most common 3L treatment) ( 80 ). A retrospective, multicenter analysis of real-world data performed in Australia found that the most frequent subsequent systemic therapy was a carboplatin-based regimen, and that some patients also received rechallenge with an ARPI or docetaxel ( 106 ). However, it was also reported that choice of subsequent treatment did not impact survival outcomes; median OS did not differ according to subsequent systematic therapy ( 106 ).…”

“…A retrospective, multicenter analysis of real-world data performed in Australia found that the most frequent subsequent systemic therapy was a carboplatin-based regimen, and that some patients also received rechallenge with an ARPI or docetaxel ( 106 ). However, it was also reported that choice of subsequent treatment did not impact survival outcomes; median OS did not differ according to subsequent systematic therapy ( 106 ). In contrast, in a single-center study, docetaxel rechallenge has shown meaningful anti-tumor activity in pretreated patients with mCRPC in the salvage setting ( 107 ).…”

“…In summary, the lack of available data to inform the delivery of appropriate treatments beyond 2L to patients with mCRPC means that the optimal sequence remains undefined ( 85 , 106 , 137 ). The data have shown that options with alternative mechanisms of action may be preferred to avoid cross-resistance between ARPIs ( 80 , 101 ).…”