Glioblastoma–We Need Better Treatments, but can we afford them?

Our non-system of care’s great virtue, we’re told, is that the profit motive encourages development of new approaches. The problem is that the profit and costs in our cost plus system of reimbursement are so great that the system and individuals can’t afford the new “advances”–which by the way are mostly of marginal benefit.

For the past thirty years in oncology we’ve been combining therapies to improve outcomes. When each of the drugs in combination cost under $1000/month, such combinations were doable. While expensive for the time, their cost does not compare with the current situation of drugs costing $10,000/month and more.

One example of what’s happening is in the treatment of glioblastom multiforme, the most malignant tumor of the brain, the disease from which Teddy Kennedy succumbed. Standard treatment used to be radiation with or without chemotherapy. Until recently the chemo was older agents that were moderately priced. With the advent of Temodar a few years ago costs have spiraled.

He will need to take 140 mg of temozolomide (75 mg/m2 per day) for 42 consecutive days. Each 140-mg capsule of temozolomide costs $283.32 ($1416.59 for 5 capsules) and the total for 42 capsules is $11,899.44. For the first cycle of metronomic temozolomide (5 days at 150 mg/m2 per day), the patient will need to take 2 of the 140-mg capsules daily for a total cost of $2833.20. For subsequent cycles of metronomic temozolomide (200 mg/m2 per day), the patient will need to take one 250-mg capsule, one 100-mg capsule, and one 20-mg capsule each day for 5 days. The prices for 5 each of the 250-mg, 100-mg, and 20-mg capsules, respectively, are $2334.29, $933.70, and $186.71. The total cost for each 5-day cycle of metronomic temozolomide at 200 mg/m2per day is therefore $3454.70.

If the same patient experiences GBM recurrence, his chemotherapy may be changed to bevacizumab and irinotecan. He will need 10 mg/kg of bevacizumab every 2 weeks. At 155 pounds, he is roughly 70 kg, so he will need 700 mg of bevacizumab. The cost of bevacizumab is $687.50 per 100 mg, so the cost of each infusion will be $4812.50.

Medicynical Note: Remember, each of these costs is for the drug alone. Additional expenses include physician’s fees, imaging costs (MRI’s, etc), other medications and nursing support.

Temozolomide has limited benefits:

Median survival in the radiation-plus-temozolomide group was 14.6 months, compared with 12.1 months in the radiation-only group. After two years, 26.5 percent of patients in the radiation-plus-temozolomide group were alive, compared with 10.4 percent of those who received radiation only. After 5 years, 9.8 percent of patients in the radiation-plus-temozolomide group and 1.9 percent of those in the radiation-only group were still alive.

And in Lancet 2009:

278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 (Medicynical note: patients who died over 5 years)

Regarding bevacizumab in glioblastoma, its use is based on small non randomized studies:

One of the trials (known as AVF3708g, or BRAIN) involved 167 patients with glioblastoma who had progressed on radiation and temozolomide (Temodar, Schering) and who then received bevacizumab either alone or in combination with irinotecan. According to an FDA analysis of the study, tumor responses were observed in 22 of 85 patients (26%) treated with bevacizumab alone, and the median duration of response was 4.2 months. (note: that’s a response in just 22 patients. The others were treated, 63 patients and had no benefit whatever)

In another trial (NCI 06-C-0064E), 56 patients with recurrent glioblastoma were treated with bevacizumab alone. Responses were observed in 11 patients (20%), and the median duration of response was 3.9 months. (Note: that’s a response of 3.9 months in the 11 patients who responded. None of the 45 other patients benefited)

There are no data so far from randomized trials for overall survival.

Medicynical Note: The question is can any system afford drugs costing tens of thousands of dollars/month? Can it afford such drugs in non curative situations? Can it afford using two such drugs simultaneously or in sequence if they provide temporary benefit for just a few of the patients treated?

Should we revisit how we develop new drugs? Revise patent law to encourage efficiency and affordability? Factor in cost efficiency when approving drugs? Consider whether our current system of granting generation long monopolies on new drugs is in the best interest of patients? Or the system?

It’s amazing but we have developed a system of drug development that is unaffordable, inefficient, and doomed.