Can Less Costly 9-Week Trastuzumab Match Efficacy of 12-Month Regimen?

A cost-effectiveness analysis found that 9 weeks of trastuzumab therapy is better than the more standard 12 months in patients with HER2-positive breast cancer, without loss of clinical efficacy. The analysis is limited, though, by the need to combine various trials rather than any head-to-head comparisons.

Trastuzumab has been shown to significantly improve survival in women with HER2-positive disease. “The budget impact of trastuzumab is high, mostly due to the drug’s high cost, and the most serious adverse effect observed is cardiac dysfunction,” wrote study authors led by Caroline Clarke, PhD, of University College London in the United Kingdom. Though 12 months is considered the standard duration of therapy, some studies have also found similar results with only 9 or 10 weeks of trastuzumab.

The new analysis incorporated cost and efficacy data from several trials; out of a total of eight randomized adjuvant trastuzumab trials in early breast cancer, a three-arm cost-effectiveness analysis was conducted based on one trial that compared 9 weeks of therapy to none, and another that compared 12 months to none. The results were published online ahead of print in PLoS One.

In terms of efficacy outcomes, the analysis found that the 9-week option was likely best. For distant disease-free survival, the probability that 9 weeks was best was 95.9%, compared with 4.1% for 12 months and 0% for no trastuzumab therapy. For overall survival, these probabilities were 88.9%, 11.1%, and 0%, respectively. For cardiac events, no therapy at all was likely best in terms of reducing risk, with a probability of 47.9%, compared with 47% for 9 weeks and 5.1% for 12-months of trastuzumab therapy.

The researchers also analyzed a four-arm cost-effectiveness analysis where a 6-month option was considered, though the trial involved was not sufficiently similar to the others to allow for a robust conclusion. Still, in that analysis, the 9-week option was still better, with the exception of cardiac dysfunction risk, where 6-months fared best.

The 9-week option also fared best on the cost-effectiveness portion. At a willingness-to-pay of £30,000 per quality-adjusted life-year (QALY) gained, which the researchers noted is toward the high end of a generally accepted threshold, the 9-week trastuzumab option yielded a net monetary benefit of £276,600 per patient. The 12-month regimen yielded a benefit of £228,185, and no treatment at all yielded a benefit of £238,882. The total QALYs gained was 10 for 9 weeks, 9.2 for 12 months, and 8.6 for no treatment.

The analysis is limited by the need to compare trials with differing methodologies, and by small numbers of patients in some trials. Still, these results, the authors wrote, “support further investigations of the hypothesis that shorter regimens may cost less and may potentially result in equivalent, if not better, clinical outcomes than the currently approved 12-month duration.”