FDA approves trastuzumab for HER2-positive gastric cancer

The Food and Drug Administration has approved trastuzumab, along with chemotherapy, to treat metastatic HER2-positive gastric cancers in people who have not been previously treated for metastatic disease.
The agency’s decision, announced late Oct. 20, follows a January move by the European Medicines Agency to grant marketing authorization to trastuzumab (Herceptin, Genentech) for the same patient group. Trastuzumab, already approved in both the United Sates and Europe for the treatment of HER2-overexpressing breast cancers, works by blocking the HER2 (human epidermal growth factor 2) protein on the surface of some cancer cells, possibly interrupting signals that make them grow.
In a phase III, manufacturer-sponsored randomized controlled trial comparing trastuzumab with chemotherapy vs. chemotherapy alone in patients with advanced gastric cancers, 22% of patients (n=594) had tumors expressing HER2 at high levels. (HER2 overexpression has been reported in between 6% and 35% of all stomach and gastroesophageal tumors.)
For these trial subjects trastuzumab added to a dual chemotherapy (capecitabine or 5-fluorouracil and cisplatin) resulted in improved overall survival of 37% over the chemotherapy alone group, with median overall survival of 13.5 vs. 11.0 months.
An updated analysis based on an additional year of follow-up showed a 25% improvement in overall survival, with a median 13.1 months in the trastuzumab arm vs. 11.7 months in the chemotherapy alone arm. (J Clin Oncol 27:18s, 2009 [suppl; abstr LBA4509])

 

The survival benefit of trastuzumab was seen to increase with the level of HER2 expressed in tumors. On September 29, England’s National Institute for Health and Clinical Excellence recommended trastuzumab to the National Health Service only for patients whose gastric tumors express the highest measurable levels of HER-2, who were seen in a subgroup of the same Phase III randomized controlled trial to have had the best survival improvement with trastuzumab. In this subgroup (n=279) overall survival was 18 months in the treatment arm compared with 12.4 months for the chemotherapy alone group, a 5.6 month improvement.