High Cost to Managing Colorectal Cancer Toxicities

Caroline Helwick

November/December 2010, Vol 1, No 6 - ESMO 2010 Conference

Milan—Because the toxicity profiles for the 3 monoclonal antibodies used in treating metastatic colorectal cancer (mCRC) differ, there are substantial differences in the cost of treating side effects, according to research presented at the 35th ESMO Congress.

“The cost of treating toxicities can inform the evaluation of the clinical and cost-effectiveness of monoclonal antibodies in managing patients with mCRC,” said lead author Chakkarin Burudpakdee, PharmD, of IMS Health in Philadelphia, a healthcare market intelligence company.

Bevacizumab, cetuximab, and panitumumab have different toxicity profiles but little is known about the direct costs for managing these toxicities. The study aimed to provide this information, he said.

A comprehensive PubMed search identified 23 phase 2 and 3 trials evaluating these agents in mCRC. American Society of Clinical Oncology and ESMO websites were searched for abstracts (years 2008-2010), and package inserts were reviewed for toxicity data.

For the purpose of estimating treatment costs for grade 3-4 toxicities, the identified toxicities were placed into representative groupings based on similarities in event type and treatment approach. For example, the “deep vein thrombosis” group included deep vein thrombophlebitis, venous thrombotic events, and thrombotic events, and “febrile neutropenia” included infection, leukopenia, and neutropenia.

Costs for the toxicities in the inpatient setting (grade 4) were estimated using 2007 Medicare payment schedules. For the outpatient setting (grade 3), in-depth clinical interviews were conducted to obtain resource use, then 2010 Medicare reimbursement rates were applied. All inpatient and outpatient costs were converted to 2010 values.

Substantial Costs for Grade 4 Side Effects
In total, 61 toxicities were identified in the studies. Clinically significant toxicities associated with bevacizumab included hypertension, arterial thrombosis, hemorrhage, gastrointestinal perforation, fistula, and wound healing complications.

Treatment related toxicities associated with cetuximab and panitumumab included skin rash, hypomagnesemia, and infusion reactions.

The inpatient cost per event for gastrointestinal perforation was the highest ($32,443), followed by fistula ($29,062), arterial thrombosis ($20,346), wound healing complications ($13,240), hemorrhage ($12,956), infusion reaction ($10,877), and hypertension ($8453). Other, less common toxicities were also costly (Table), but skin rash and hypomagnesemia—which occurred with cetuximab and panitumumab— were among the least costly inpatient toxicities at $4424 and $6174, respectively, Dr Burudpakdee reported.

For outpatients, costs were minimal, ranging from $185 for hypertension and rash to $585 for wound healing complications.

Dr Burudpakdee acknowledged the study’s limitations. The development of a comprehensive and standardized list of toxicities is limited by the variability among the trials (eg, sample sizes and differences in reporting or defining grade 3-4 adverse events of interest). Outpatient resource use was based on best clinical judgment and may not reflect all clinical practices, nor does it include outpatient drug use.