Cost-Effectiveness of Trastuzumab in Gastric Cancer Questioned

Zosia Chustecka

August 20, 2010

August 20, 2010 — Data on trastuzumab (Herceptin, Roche) in gastric cancer — hailed as practice-changing when announced last year — were published online August 20 in The Lancet. But an accompanying editorial asks whether the practice changes suggested by the results are affordable.

The new data, from the manufacturer-sponsored Trastuzumab for Gastric Cancer (ToGA) trial, established that some gastric cancers are HER2-positive, and showed that in these cases adding trastuzumab — which specifically targets HER2 — to chemotherapy significantly improves survival.

When the data were first presented, at the 2009 annual meeting of the American Society for Clinical Oncology (ASCO), the finding was welcomed enthusiastically by gastrointestinal oncologists.

"Until these data came out, we didn't know that we had to consider HER2 in stomach cancer," said outgoing ASCO president Richard Schilsky, MD, professor of medicine at the University of Chicago in Illinois, and a specialist in gastrointestinal cancers.

"These results will quickly have an impact on the management of patients," Dr. Schilsky predicted. He and several other experts agreed with the recommendation from ToGA principal investigator Eric Van Cutsem, MD, from University Hospital Gasthuisberg in Leuven, Belgium, that the HER2 status of all patients with advanced gastric cancer be tested and that those found to be positive be treated with a combination of trastuzumab and chemotherapy.

In the published paper, the researchers conclude that, on the basis of these data, trastuzumab combined with chemotherapy can be considered a new standard option for patients with HER-positive advanced gastric cancer.

However, the accompanying editorial questions the cost-effectiveness of such treatment, and looks at the way the results from ToGA would translate into practice.

Editorialists Alistair Munro, MD, and Paddy Niblock, MD, from the Department of Surgery and Molecular Oncology at Ninewells Hospital in Dundee, Scotland, describe the benefit from trastuzumab as "modest" and highlight the high cost of the drug.

Trastuzumab is so expensive that the cost of using it in 1 gastric cancer patient to extend survival by a few months is equivalent to the total annual healthcare spend of several individuals (how many depends on locale), they point out.

This raises an important moral question. They ask: "What is the justification for introducing a treatment that might enable 1 individual to live a few months longer, but will consume, for each person treated, the total yearly health expenditure for scores of their fellow citizens?"

Absolute Benefit Is Small

The ToGA trial involved 584 patients with HER2-positive advanced gastric or gastroesophageal junction cancer. The results showed a significant improvement in survival in patients who received trastuzumab in addition to chemotherapy; they had a median overall survival of 13.8 months, compared with 11.1 months for those who received chemotherapy alone (hazard ratio, 0.74; P = .0046).

The researchers note that this corresponds to a 26% reduction in the death rate. They also point out, in the introduction to their paper, that the median overall survival for patients with advanced gastric cancer is less than a year.

But the editorialists say that the absolute benefits from adding trastuzumab to chemotherapy in advanced gastric cancer are small; median survival was prolonged by 11 weeks and disease progression was delayed by a median of 5 weeks.

In addition, the survival curves do not indicate that trastuzumab saves lives, they point out; the longer-term survival rates were similar in both groups.

The small benefit gained comes at a very high financial cost, they emphasize. Patients in the ToGA trial were treated with trastuzumab every 3 weeks until disease progression, and the median time to progression was 6.7 months. They estimate that this would work out at an average cost of £13,857 per patient (around $21,598 in current US dollars).

In the 24 countries that contributed patients to the ToGA trial, including Australia, China, India, Korea, South Africa, the United States, as well as European countries, the total annual health expenditure per citizen varies from $40 to $5500 (calculated in 2007 US dollars), the editorialists note.

Hence, they estimate that the cost of treating 1 patient in the ToGA trial is the equivalent to the total annual health spending for 3 people in the United States, for about 5 to 10 people in many European countries, about 120 people in Peru, nearly 200 people in China, and 500 people in India.

Results From Industry-Sponsored Trials

Broadening their arguments further into the field of cancer, the editorialists point out that the modest benefit seen from the addition of trastuzumab to chemotherapy in gastric cancer is similar to that seen for other targeted agents in other cancers, including cetuximab (Erbitux) in head and neck cancer and bevacizumab (Avastin) in colorectal cancer.

All of these results came from industry-sponsored trials, they note, motivated by the opening up of new markets for these drugs.

"For research into cancer treatment, scientifically important questions often remain unasked because no commercial benefit will be gained from answering them," Drs. Munro and Niblock write.

"There is a lot of evidence on the effects of adding expensive new drugs to conventional therapies, but little evidence for when older, less expensive interventions are combined," they write. "The evidence we have might not be the evidence we need, and the evidence we need may never become available."

The ToGA trial was funded by Roche, the manufacturer of trastuzumab. Several of the study authors report acting as consultants to and receiving grants from Roche, and 3 are company employees; other relevant financial relationships, including honoraria received from other pharmaceutical companies, are listed in the paper. Dr. Munro has disclosed no relevant financial relationships. Dr. Niblock reports receiving travel and accommodation expenses from Merck-Serono.

Lancet. Published online August 20, 2010.


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