Action Points
- Explain to interested patients that new drugs used for metastatic colorectal cancer extend survival compared with older agents, but also are more expensive.
The newer agents used against metastatic colorectal cancer are associated with increased survival, and although the costs are substantial, they fall within the range of most willingness-to-pay estimates, researchers said.
Between 1995 and 2005, life expectancy among patients with advanced colorectal cancer increased by 6.8 months and lifetime costs increased by $37,100, with the implied cost per life-year gained being $66,200 (95% CI $48,100 to $84,200), according to David H. Howard, PhD, and colleagues from Emory University in Atlanta.
After adjustment for patients' health utility and out-of-pocket expenses, the incremental cost per quality-adjusted life-year gained was $99,100 (95% CI $72,300 to $125,900), the researchers reported online in the Archives of Internal Medicine.
The newer agents approved for metastatic colorectal cancer, particularly the monoclonal antibodies bevacizumab (Avastin) and cetuximab (Erbitux), have been singled out as examples of high-cost, low-value therapies.
For example, in randomized trials the authors reviewed bevacizumab treatment was associated with a survival increase of only three to five months and a monthly cost in excess of $8,000.
To evaluate the cost-effectiveness of the new drugs in clinical practice, Howard and colleagues compared the change in costs with changes in survival time in a sample of patients drawn from the Surveillance, Epidemiology, and End Results database.
The sample consisted of 12,473 patients ages 66 and older who received a diagnosis of stage IV colorectal cancer.
Patients were divided into five groups according to date of diagnosis, with the first period, January 1995 to May 1996, reflecting life expectancy and cost before the newer drugs were available.
Subsequent time period cutoffs followed the approval of irinotecan (Camptosar) in June 1996, capecitabine (Xeloda) in April 1998, and oxaliplatin (Eloxatin) in August 2002.
The final period followed the licensure of bevacizumab and cetuximab in February 2004.
Among the 4,665 patients (37.4%) who received treatment with chemotherapy or targeted therapy within six months of their diagnosis across all time periods, median survival increased by 4.5 months, and costs in the two-year window after diagnosis increased by $17,800.
Three-year survival rates increased during the 10-year study period, from 11.7% in the first period to 19.1% in the final period.
Median survival time among patients diagnosed in the first period was 11.6 months, compared with 16.1 months in the last period (P<0.001).
Costs incurred in the two years after diagnosis in these patients grew from $56,600 in the first period to $81,000 in the last (P<0.001).
In contrast, among the 7,808 patients who did not receive drug therapy, median survival decreased slightly, from 2.9 months to 2.5 months (P=0.54), and costs increased only slightly, from $38,400 to $39,600 (P=0.13).
The investigators noted that they were unable to measure changes in patient quality of life across the different time periods, but stated that it has probably improved.
"Newer agents delay tumor progression and increase the proportion of remaining survival time spent in a progression-free state," they wrote.
The median survival time of 16.1 months among chemotherapy patients contrasts with median survival times beyond 20 months for regimens containing bevacizumab, as seen in recent clinical trials.
A possible explanation for this discrepancy, according to the investigators, is that not all patients in the last period received the newest drugs.
"Also, it is not uncommon to see a lower magnitude of benefit when clinical trial regimens are applied in real-world settings to a broader patient population," they noted.
Similarly, the lifetime increase in cost of only $37,000 is far less than cost estimates typically cited in the media and in journal commentaries, the investigators said.
Again, not every patient received the costliest drugs. "Our estimates of the change in survival and costs are lower than they would be if all patients treated with chemotherapeutic or targeted agents received the newest agents," they acknowledged.
The authors pointed out that the sample also didn't include patients who initially were diagnosed with nonmetastatic cancer and later received chemotherapy when they metastasized, so the population was not representative of the entire spectrum of patients treated with the newer anti-cancer agents.
They noted that these drugs would probably face close scrutiny if payers such as Medicare were to include cost-effectiveness in decision-making -- even though the cost per quality-adjusted life-year of about $100,000 is within the range of most willingness-to-pay thresholds.
They also offered a cautionary note: "Continuation of Medicare's open-ended coverage policy for new agents and other expensive technologies will prove difficult to sustain as costs for the program continue to rise."