Steroid SWITCHing may benefit mCRPC patients who progress on abiraterone
medwireNews: A phase II proof-of-concept study has shown that clinically stable patients with metastatic castration-resistant prostate cancer (mCRPC) and limited disease progression during treatment with abiraterone acetate plus prednisone can experience biochemical and radiologic responses following a steroid switch to dexamethasone.
The SWITCH trial included 26 men who had biochemical progression (with or without limited radiologic progression) after no less than 12 weeks of treatment with abiraterone 1000 mg once daily plus prednisone 5 mg twice daily. The participants were maintained on the same dose of abiraterone while their steroid was changed to dexamethasone 0.5 mg/day.
At 6 weeks after the switch, 12 (46.2%) men showed a decline in prostate-specific antigen (PSA) levels of at least 30% (PSA30 response), while PSA levels declined by at least 50% (PSA50 response) in eight (34.6%) men after at least 12 weeks.
The median biochemical progression-free survival (PFS) after the steroid switch was 5.3 months, and median radiographic PFS was 11.8 months. Two men achieved a partial radiographic response as per RECIST criteria and median overall survival was 20.9 months.
The researchers highlight that “[t]his extension of time on therapy associated [with] a clinical benefit is a meaningful therapeutic objective.”
Furthermore, 12 patients received at least one taxane (mostly docetaxel) following abiraterone plus dexamethasone, with 50% achieving a PSA50 response after at least 12 weeks of treatment, indicating that the steroid switch “did not compromise subsequent taxane therapy,” the team notes in the British Journal of Cancer.
Importantly, Elena Castro (Spanish National Cancer Research Centre, Madrid) and colleagues found that the switch to dexamethasone did not add any significant toxicities over prednisone. At least one grade 1 or 2 related adverse event was experienced by 31% of men after the switch, but there were no grade 3 or 4 adverse events.
Biomarker studies showed that the positive effects of the switch on outcomes varied by androgen receptor (AR) gene status, with 100% of the six patients with wild-type AR experiencing a PSA30 response and 50% showing a PSA50 response. By contrast, none of the five patients with AR copy number gain had a PSA response, and these patients also had significantly shorter biochemical PFS (median 2.8 vs 8.3 months) and radiographic PFS (median 7.9 vs 19.5 months) than those who were wild-type for AR.
“Confirmation of our results in additional cohorts would allow the selection of patients likely to benefit from the steroid switch,” say Castro and co-investigators.
They conclude that “[this] study provides prospective evidence that a steroid switch is a feasible and safe manoeuvre that can induce responses in clinically stable patients progressing on abiraterone.”
The team continues: “Nonetheless, these findings require further validation, ideally in a prospective randomised clinical trial.”
By Catherine Booth
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