Cabazitaxel [
10] is a novel taxane-class cytotoxic agent [
31] that has shown efficacy in model system tumors that are resistant to paclitaxel and docetaxel [
32,
33]. In a recently published, randomized, multicenter, phase 3 trial, the efficacy and safety of cabazitaxel and prednisone were compared with those of mitoxantrone and prednisone for the treatment of mCRPC that had progressed following docetaxel-based chemotherapy [
10]. A total of 755 patients were randomly assigned to treatment with cabazitaxel (N = 378) or mitoxantrone (N = 377), and the median follow-up for both treatment groups was 12.8 months [
10]. Kaplan-Meier analysis demonstrated a significant benefit in OS for patients assigned to cabazitaxel, with a significant (P < 0.0001) 30% reduction in death (HR = 0.70; Table
1); the median OS was 15.1 months with cabazitaxel, compared with 12.7 months with mitoxantrone. The composite endpoint of median PFS (defined as the time between randomization and first date of PSA progression, tumor progression, pain progression, or death) also favored the cabazitaxel arm (2.8 vs 1.4 months; P < 0.0001). Tumor response (14.4% vs 4.4%; P = 0.0005) and PSA response (39.2% vs 17.8%; P = 0.0002) also significantly favored cabazitaxel, as did median time to tumor progression (8.8 vs 5.4 months; P < 0.0001) and median time to PSA progression (6.4 vs 3.1 months; P = 0.001). Pain response and time to pain progression were similar between the treatment groups [
10]. Hematologic toxicities (neutropenia, leukopenia, anemia) were the predominant grade 3 or higher AEs associated with cabazitaxel in the study; the most common clinical grade 3 or higher AEs were febrile neutropenia and diarrhea. Grade 3 neuropathy was uncommon (1% for cabazitaxel). The findings of TROPIC established cabazitaxel as the first agent to prolong survival in the post-docetaxel space, with a 30% reduction in death over mitoxantrone [
10]. On the basis of these data, cabazitaxel has been approved by the US Food and Drug Administration for use in patients with mCRPC who have progressed after docetaxel [
34]. Results of subgroup analysis in TROPIC also should be mentioned, as these showed a benefit of cabazitaxel over mitoxantrone in patients progressing during docetaxel treatment and in those receiving more prolonged dosing with docetaxel [
10]. In the TROPIC trial, the median time from last docetaxel dose to progression was less than one month; also, these patients were heavily pretreated with a median of 7 cycles of docetaxel pre-TROPIC enrollment. Still, it should be noted that cabazitaxel can be associated with substantial toxicity, and deaths within 30 days of the last dose were reported in 4.9% of patients. This toxicity was primarily related to myelosuppression, but diarrhea could also be severe. First cycle monitoring with weekly CBC is recommended and primary prophylaxis with G-CSF is recommended for men over the age 65 and for those with a poor performance status, previous episodes of febrile neutropenia, extensive prior radiation ports, poor nutritional status, or other serious comorbidities [
35].
Table 1
Currently proven treatment options for mCRPC patients in the post-docetaxel space [
9,
10]
Abiraterone acetate + prednisone (COU-AA-301)
| Antiandrogen (prednisone/placebo) | Median OS = 14.8 vs 10.9 mo (HR = 0.65) | 0.54-0.77 | < 0.0001 |
| | Median TTPP = 10.2 vs 6.6 mo (HR = 0.58) | 0.46-0.73 | < 0.0001 |
| | Median rPFS = 5.6 vs 3.6 mo (HR = 0.67) | 0.58-0.78 | < 0.0001 |
| | PSA response: 38% vs 10% | - | < 0.0001 |
Cabazitaxel + prednisone (TROPIC)
| Chemotherapy (mitoxantrone/pred-nisone) | Median OS = 15.1 vs 12.7 mo (HR = 0.70) | 0.59-0.83 | < 0.0001 |
| | Median PFS = 2.8 vs 1.4 mo (HR = 0.74) | 0.64-0.86 | < 0.0001 |
| | Tumor response = 14.4% vs 4.4% | - | 0.0005 |
| | PSA response = 39.2% vs 17.8% | - | 0.0002 |