Metastatic CRPC Taxane Response Independent of AR-V7 gene

Patients with metastatic castration-resistant prostate cancer who express AR-V7 in circulating tumour cells may benefit from taxane chemotherapy over enzalutamide or abiraterone treatment

medwireNews: Genotyping castration-resistant prostate cancer (CRPC) for the androgen receptor splice variant 7 gene (AR-V7) could help guide treatment decision-making, suggest US researchers.

Prior research indicated that AR-V7 was associated with a significantly poorer response to the androgen receptor antagonist enzalutamide and the cytochrome P17 inhibitor abiraterone, explain Emmanuel Antonarakis, from Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland, and co-workers.

Now, the team reports in JAMA Oncology that 17 men with measurable levels of AR-V7 in their circulating tumour cells had comparable progression-free survival (PFS) and prostate-specific Antigen (PSA) PFS outcomes to docetaxel or cabazitaxel to 20 men who tested negative for the protein.

A PSA response was noted for 41% and 65% of patients positive and negative for AR-V7, respectively, but this difference was not significant.

“Detection of AR-V7 in [circulating tumour cells] from men with metastatic CRPC is not associated with primary resistance to taxane chemotherapy”, they write.

Of note, 25% of the eight patients who had not previously used enzalutamide or abiraterone were positive for AR-V7 compared with 50% of the 14 men who had used one of these drugs and 55% of the 15 patients who had received both agents.

Combining the original data for the 62 men given enzalutamide or abiraterone with the latest group, the team found that AR-V7-positive patients were significantly more likely to achieve a PSA response on taxanes than on either drug (41 vs 0%).

And both PFS and PSA PFS were significantly longer with taxane chemotherapy than the other agents, with hazard ratios of 0.21 and 0.19, respectively. 

By contrast, clinical outcomes did not differ between the treatment groups for men who were negative for AR-V7.

“If confirmed in larger-scale clinical trials, AR-V7 status could emerge as the first treatment selection Biomarker for CRPC”, the researchers write.

Mary-Ellen Taplin and Steven Balk, from Harvard Medical School in Boston, Massachusetts, emphasise the need for further study for the relationship between AR-V7 and all three treatment options in an accompanying editorial, writing that “this conclusion should be considered hypothesis generating until further studies can confirm that abiraterone and enzalutamide are ineffective in AR-V7-positive tumors.”

They urge caution, noting that, “given the tradeoffs with respect to toxicity, clinicians should await results of ongoing clinical trials before incorporating AR-V7 measurements into their treatment decisions.”

References

Antonarakis ES, Lu C, Luber B, et al. Androgen receptor slice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncol 2015; Advance online publication 4 June. doi:10.1001/jamaoncol.2015.1341

Taplin M-E, Balk SP. Has the time arrived for biomarker-directed therapy in castration-resistant prostate cancer. JAMA Oncol 2015; Advance online publication 4 June. doi:10.1001/jamaoncol.2015.1457

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