October 22 2010 — Trastuzumab (Herceptin, Roche) has been approved by the US Food and Drug Administration for use in the treatment of HER2-positive gastric cancer in the United States. This indication was approved in Europe earlier this year.
This is a label extension for trastuzumab, which is already marketed for use in the treatment of HER2-positive breast cancer.
Approval for the gastric cancer indication was based on results from a single clinical trial, the company-sponsored phase 3 ToGA study. The trial of 594 patients with HER2-positive advanced gastric cancer showed that the addition of trastuzumab to chemotherapy significantly improved overall survival, from 11.1 months to 13.8 months (hazard ratio, 0.7, P = .0046).
Although trastuzumab was rapidly accepted in the treatment of breast cancer, this new indication has stirred up controversy over the small benefit for a high cost.
There is also a question about how relevant the data coming out of the ToGA study are for patients with gastric cancer in the United States. The trial was conducted in 24 countries, including those in Europe, Latin America, and South Africa, but the majority of patients were from Asia. "We know that gastric cancer in Asia is a different disease from that seen in Westerners," said John Marshall, MD, chief of the Division of Hematology/Oncology at Georgetown University, Washington, DC. Dr. Marshall, who writes the Marshall on Oncology videoblog on Medscape Medical News, was not involved in the ToGA study.
Hailed as Practice-Changing
These reactions are quite a contrast to the enthusiasm that greeted the ToGA results when they were first presented at the 2009 annual meeting of the American Society of Clinical Oncology (ASCO). Hailed by several experts at the meeting as "practice changing," they were also listed by ASCO as one of the major advances in cancer in 2009.
In discussing the results after their presentation at that meeting, David Cunningham, MD, from the Royal Marsden Hospital, Surrey, United Kingdom, said that the 2.7-month improvement in overall survival seen in ToGA is "modest," but he argued that it "is clinically meaningful in this group of patients with a poor prognosis." As a result, he recommended that trastuzumab plus chemotherapy be considered for all HER2-postive gastric cancer patients, and several experts at the meeting enthusiastically agreed, as reported at the time by Medscape Medical News.
Benefit and Cost-Effectiveness Questioned
However, when the results of the ToGA trial were published in the Lancet earlier this year (2010;376:687-697), the accompanying editorial (Lancet. 2010;376:659-660) was scathing in its questioning of both benefit and cost-effectiveness.
Editorialists Alistair Munro, MD, and Paddy Niblock, MD, from the Department of Surgery and Molecular Oncology at Ninewells Hospital in Dundee, Scotland, also described the benefit as "modest," but they highlighted the high cost of the drug.
The absolute benefits from adding trastuzumab to chemotherapy in advanced gastric cancer are small, they write. 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 works out to an average cost of £13,857 per patient (~US$21,598).
Using 2007 data for total annual healthcare expenditure per citizen, they estimate that the cost of treating 1 patient in the ToGA trial is equivalent to the total annual healthcare spend 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.
This raises an important moral question, they note. "What is the justification for introducing a treatment that might enable 1 gastric cancer patient to live a few months longer, but will consume, for each person treated, the total yearly health expenditure for scores of their fellow citizens?"
The ToGA trial was funded by Roche, the manufacturer of trastuzumab. Several of the study authors report acting as consultants and receiving research grants from Roche, and 3 are company employees. Dr. Munro has disclosed no relevant financial relationships. Dr. Niblock reports receiving travel and accommodation expenses from Merck-Serono. Dr. Marshall reports receiving grants for clinical research and for educational activities, and serving as an advisor or consultant to Roche, Sanofi, Pfizer, Genentech, Bristol-Myers Squibb, and Amgen.
Medscape Medical News © 2010 WebMD, LLC
Send press releases and comments to email@example.com.
Cite this: Trastuzumab for HER2-Positive Gastric Cancer Approved in US, But Should It Be Used? - Medscape - Oct 22, 2010.