Roche wish to announce that the European Commission has approved Herceptin (trastuzumab) in combination with capecitabine or 5-fluorouracil and cisplatin for use in patients with HER2-positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction who have not received prior anti-cancer treatment for their metastatic disease. The approval is based on the strong results from the ToGA trial, which showed that treatment with Herceptin significantly prolongs the lives of patients with this aggressive cancer. The submission for the label extension was reviewed in an accelerated process by the European Health Authorities, allowing patients to benefit sooner from this life-extending treatment.
Stomach cancer is the second most common cause of cancer-related death in the world and is the fourth most commonly diagnosed cancer, with over 1,000,000 cases of stomach cancer diagnosed each year.(1) Metastatic stomach cancer is associated with a poor prognosis; the median survival time after diagnosis is approximately 10-11 months with currently available therapies. Approximately 15- 18% of stomach tumours show high levels of HER2.(2)
Herceptin is a humanised antibody, designed to target and block the function of HER2. The mode of action of Herceptin is unique in that it activates the body’s immune system and suppresses HER2 to target and destroy the tumour. Herceptin has demonstrated unprecedented efficacy in treating both early and metastatic HER2- positive breast cancer. Given in combination with or following standard chemotherapy, Herceptin has been shown to improve response rates, disease-free survival and overall survival while maintaining quality of life in women with HER2-positive breast cancer.(3-8)
The ToGA Study (9)
The ToGA study is the first randomised Phase III trial investigating the use of Herceptin in patients with inoperable locally advanced, recurrent and/or metastatic HER2-positive gastric cancer. The rationale for conducting this trial was based on the knowledge that targeted therapy with Herceptin has demonstrated unprecedented efficacy in the treatment of HER2-positive breast cancer. In addition, the overexpression of HER2 was also observed in stomach cancer.
Study Design
Approximately 3,800 patients were tested for HER2-positive tumours and 594 patients with HER2-positive disease were enrolled into the study. Patients were randomised to receive one of the following regimens as their first line of treatment:
• A fluoropyrimidine (Xeloda or intravenous 5-FU) and cisplatin every 3 weeks for 6 cycles. Most patients were receiving Xeloda and cisplatin as chemotherapy.
• Herceptin 6mg/kg every 3 weeks until progression in combination with a fluoropyrimidine and cisplatin for 6 cycles.
The primary objective of the study was to demonstrate superiority in overall survival of the Herceptin-containing treatment arm compared to the chemotherapy alone arm. The pre-planned interim analysis was triggered by the occurrence of 347 events.
Secondary endpoints for the study included progression-free survival, overall response rate, duration of response, safety and quality of life.
Herceptin Significantly Increases Survival
The overall results of the ToGA study were as follows:
• For overall survival, the Hazard Ratio was 0.74 (CI 0.60-0.91) with a highly significant p-value of p=0.0046. Herceptin increased the median overall survival time by 2.7 months to 13.8 months.
• The response rate was increased with Herceptin from 34.5% to 47.3%.
• For patients with tumours exhibiting high levels of HER2, overall survival in the study was 16 months on average vs. 11.8 months for patients receiving chemotherapy alone.
• No new or unexpected side effects were observed.
Conclusion
“Herceptin is the first targeted biological therapy to show a survival benefit in metastatic gastric cancer and represents a significant advance in the treatment of this devastating disease”, said Pascal Soriot, Chief Operating Officer (COO), Roche Pharmaceutical Division. “We believe that Herceptin will help patients with HER2-positive metastastic gastric cancer, as much as it has helped so many women with HER2-positive breast cancer.”
Commenting on the approval of the label extension of Herceptin for HER2-positive metastatic gastric cancer, one of the lead investigators of the ToGA trial, Professor Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium, said: “I am delighted that the approval will make Herceptin available to patients with HER2-positive metastatic stomach cancer across Europe. The approval of Herceptin for HER2-positive metastatic stomach cancer represents an important advance for the treatment of these patients. Clinicians will need to ensure that patients with metastatic stomach cancer are accurately tested for HER2 overexpression.”
References: 1- American Cancer Society. Global Cancer Facts & Figures. 2007.
2- Hofmann M. et al. Histopathology 2008. 52(7):797-805.
3- Slamon DJ et al. N Engl J Med. 2001. 344(11):783-92.
4- Marty M et al. J Clin Oncol. 2005. 23(19):4265-74.
5- Vogel CL et al. Oncology. 2001. 61 Suppl 2:37-42.
6- Piccart-Gebhart M et al. N Engl J Med. 2005. 353(16):1659-72.
7- Romond, E et al. N Engl J Med. 2005. 353(16):1673-84.
8- Osoba, D et al. J Clin Oncol. 2002. 20(14):3106-13.
9- Van Cutsem et al. J Clin Oncol. 2009. 27:18s (suppl:abstr
LBA4509).
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