Oncology drugs are expensive enough on their own. When they start getting used in succession, the cost per patient can really start to add up, causing companies to feel pushback from payers.

Insurers can't exclude the use of oncology drugs since many states forbid it and as Rhonda Greenapple, CEO of Reimbursement Intelligence, pointed out, "It wouldn't be a good headline in the news."

But insurers can shift the cost onto patients in the form of higher copays, deductibles, and premiums. And they can put obstacles in the way to make it harder for doctors to prescribe multiple treatments.

In a survey of 50 pharmacy and medical directors at national and region plans by Reimbursement Intelligence, 47 percent of respondents indicated that they plan to tightly manage the use of Xtandi (enzalutamide, Astellas Pharma Inc. and Medivation Inc.) and Zytiga (abiraterone, Johnson & Johnson) in prostate cancer patients requiring prior authorization before allowing the drugs to be used.

Only 14 percent of plans had no restrictions on their use, while 10 percent required doctors to follow the compendium listing, which Greenapple classified as "no big deal."

Xtandi is approved for metastatic castration-resistant prostate cancer patients who have previously received docetaxel not after Zytiga, which wasn't approved as a first-line therapy when Medivation was running its pivotal trial. But there's plenty of off label use in the oncology field, facilitated by compendiums such as the National Comprehensive Cancer Network Drugs & Biologics Compendium. "They're the bible for allowing use off label," Greenapple.

Some insurers have instituted their own recommended pathways to establish the order in which drugs should be used, and 14 percent of insurers required doctors follow their pathways to get coverage for Zytiga and Xtandi.

Some insurers outsource the establishment of pathways to a company such as P4 Pathway, part of Cardial Health Inc. Other insurers base their pathways on the American Society of Clinicial Oncology's Quality Oncology Practice Initiative.

However the insurers set up their pathways, Greenapple stressed that doctors are still a key part of the process and therefore a group that drug companies need to focus on when advocating for coverage. "You must engage the oncologists because if you shove it down their throats, it's not going to work," Greenapple told BioWorld Insight.

National insurers were more likely to put up roadblocks to the use of multiple prostate cancer drugs. Most striking, 25 percent of national insurers require failure on Zytiga before prescribing Xtandi, while only 9 percent of the regional insurers had that restriction. Greenapple chocked the difference up to national plans having more ability to control the dispensing of drugs at retail pharmacies.

The restrictions on using Zytiga and Xtandi should give Dendreon Corp. pause. The biotech is running a clinical trial comparing the concurrent use of Provenge (sipuleucel-T) and Zytiga compared to sequential use of the two prostate cancer treatments. The company has indicated plans to run a similar trial combining Provenge with Xtandi.

The buy-and-bill model for doctors to get reimbursed for Provnege makes it harder for insurers to shift the cost onto patients compared to Zytiga and Xtandi, which are oral medications where insurers can institute a high copay at the pharmacy. Companies can counteract that by covering much or all of the patients copay, although that option isn't available for patients on Medicare.