Docetaxel Becomes the First Treatment Choice Post-Abiraterone in 50% of Patients with mCRPC

Docetaxel First Treatment mCRPC

Thomas W. Flaig, MD

A post hoc analysis of the phase III COU-AA-302 clinical trial suggests docetaxel can produce antitumor activity as the first subsequent therapy following disease progression with abiraterone acetate in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC).

“This observation suggests that docetaxel may be considered for mCRPC patients who progress with abiraterone acetate,” said Thomas W. Flaig, MD, associate professor, University of Colorado Cancer Center, who presented his data at the 2016 Genitourinary Cancers Symposium.

COU-AA-302 was a phase III, randomized, double-blind study where chemotherapy-na&iuml;ve men with mCRPC showcased significantly improved radiographic progression-free survival (HR, 0.52; P <.0001) and overall survival (34.7 months vs 30.3 months; P = .0033) when treated with abiraterone acetate plus prednisone compared with placebo/prednisone. An analysis of treatment patterns showed docetaxel was the first subsequent therapy in about half of men in both the abiraterone acetate and placebo arms of COU-AA-302.

Despite frequent use of sequential therapy in practice, information is limited on subsequent therapy following treatment with abiraterone acetate, prompting this retrospective analysis, said Flaig.

&ldquo;For about 10 years, everyone was using docetaxel first and then trying out things after. Abiraterone acetate was initially approved post-docetaxel,&rdquo; he said. &ldquo;This was a trial [COU-AA-302] that gave it pre-chemotherapy, but what happens next? The whole paradigm has shifted. For the most part, it&rsquo;s docetaxel. Roughly half the patients, after abiraterone, go on to docetaxel.&rdquo;

Data for the current analyses were collected at the final overall survival analysis.

Sixty-seven percent of patients in the abiraterone arm and 80% in the placebo arm received any subsequent therapy. Docetaxel was the most common first subsequent therapy in either arm, used in 48% of the abiraterone arm and 50% of the placebo arm. The median duration of docetaxel following abiraterone treatment was 3 months.

Progression of PSA level was cited by investigators as the most common reason for discontinuation of docetaxel (29%). An adverse event was cited by only 16% as the reason for stopping docetaxel. &ldquo;There was some concern whether there would be a toxicity issue, but toxicity was not an issue,&rdquo; said Flaig. &ldquo;Toxicity was not a reason that patients came off this.&rdquo;

Efficacy analysis was performed among the 100 patients from the abiraterone acetate arm who had available baseline PSA levels within 30 days of docetaxel as first subsequent therapy and at least one post-baseline PSA value. Among these 100 patients, 40% had a &ge;50% reduction in PSA with first subsequent docetaxel therapy, with 27% having a confirmed &ge;50% reduction in PSA.

&ldquo;We see that the PSA responses are fairly robust with docetaxel,&rdquo; said Flaig. One of the issues is that this is a retrospective collection of data, which was prescribed and planned, but it&rsquo;s not part of the trial so there&rsquo;s a good chance we couldn&rsquo;t confirm some of those responses just because we weren&rsquo;t able to get the data points.&rdquo;

Flaig and colleagues also looked at treatment patterns among older (&ge;75 years) and younger (<75 years) patient subgroups who progressed on abiraterone.

While docetaxel was the most common first subsequent therapy for both younger and older men in each treatment arm, the older men in each arm were less likely to receive it. In the abiraterone arm, 55% of the younger group received docetaxel as first subsequent therapy compared with 35% of those &ge;75 years. In the placebo arm, these percentages were 56% and 38%, respectively. In the group of patients &ge;75 years, 43% who progressed on abiraterone acetate did not receive subsequent therapy for mCRPC following discontinuation of the protocol-specified study drug.

The researchers noted that their findings, although retrospective, support further investigation of subsequent therapy options for patients with mCRPC after treatment with abiraterone acetate.

References

1. Flaig TW, Smith MR, Saad F, et al. Treatment patterns after abiraterone acetate in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): post hoc analysis of COU-AA-302. Presented at: 2016 Genitourinary Cancers Symposium; January 7-9, 2016; San Francisco, CA. Abstract 168.