On August 13, 2013 I wrote an important post about the terrible practice beginning to rear its head called step therapy. Step therapy is the practice of insurance companies requiring less expensive drugs be prescribed prior to more expensive ones despite the comparative efficacy of the drugs and their different mechanisms of action. This practice allows insurance companies to prescribe what medications we are given despite the medical opinion of our doctors.

The specific situation I described in the August 13th post spoke specifically about some insurance company’s current practice of requiring Zytiga (Abiraterone Acetate) prior to Xtandi (Enzalutamide) despite the recommendation of our doctor’s best medical judgment.

A recent but small study (size being one of the major limiting factors of this study) was released in the Journal European Urology that examined the sequencing of Zytiga before Xtandi. For 35% of the men the sequencing made their eventual treatment with Xtandi ineffectual!

In the study thirty-five patients were identified as having received sequential therapy with abiraterone followed by enzalutamide. All patients had undergone prior docetaxel chemotherapy, and no patient had received ketoconazole.

The researchers used post treatment changes in prostate-specific antigen (PSA) we to determine the activity of enzalutamide in the men who had received prior abiraterone.

The median duration of abiraterone treatment was 9.0 month (range: 2.0–19.0 month).

Of the 35 patients, 16 (45.7%) achieved a >50% decline in PSA, and 14 (40%) had a rising PSA as the best response.

The median duration of subsequent enzalutamide treatment was 4.9 month (Kaplan-Meier estimate; 95% confidence interval

[CI], 2.4–7.4).

Seven of 16 CRPC patients who were initially abiraterone-sensitive (43.8%) and 3 of 19 CRPC patients who were initially abiraterone-insensitive (15.8%) showed a >50% PSA decline while taking enzalutamide.

Of the 35 patients, 17 (48.6%) were primarily enzalutamide-resistant and showed a rising PSA as the best response.

Median time to progression was 4.0 months (95% CI, 2.0–6.0) for 18 of 35 patients with at least one declining PSA value while taking enzalutamide (51.4%).

Of the 17 patients who were assessable radiologically, only 1 (2.9%) attained a confirmed partial response.

In this study Xtandi treatment achieved only a modest response rate in patients progressing after having received Zytiga. Although cross-resistance between abiraterone and enzalutamide was a common phenomenon, it was not inevitable, and a small but significant number of patients showed significant benefit from sequential treatment.

This study suggests that step therapy is inappropriate for 1/3 of men who have mCRPC and have also progressed after treatment with docetaxel-based chemotherapy. When you add on the fact that for some men the use of prednisone (which is required to be used along with Zytiga) is also inappropriate we have to conclude that step therapy without good scientific understanding could actually harm us.

We would not be in this situation if pharma would concurrently develop reliable biomarkers for efficacy in their treatments so we could begin to accurately predict what drugs would best be suited for what man. U

The insurance companies and the pharmaceutical (pharma) companies that use step therapy or promote their drug and the cheapest drugs are just being greedy at our expense.

I do think that when pricing the newly approved drug treatments pharma must also put their feet back on the ground and realize that they are exploiting us and the insurance companies. If a drug is over priced or if an insurance company institutes inappropriate step therapy requirements it’s the patients who pay the price, both with our health and with our pocketbooks.

Joel T. Nowak, M.A., M.S.W.