Genentech yesterday confirmed that FDA has cleared Herceptin® (trastuzumab) used in combination with chemotherapy for the treatment of Her2-positive metastatic stomach or gastroesophageal junction cancer in patients who have not previously received treatment for metastatic disease. Use of a Herceptin-chemotherapy combination for treating metastatic gastric cancer was sanctioned by the European regulatory authorities back in January.
The latest U.S. approval was based on data from the pivotal ToGA trial involving 594 patients with locally advanced or metastatic Her2-positive stomach cancer. Patients received either Herceptin and chemotherapy (cisplatin plus either capecitabine or 5-FU), or chemotherapy alone. The data showed Herceptin combination therapy boosted overall survival by 37% compared with chemotherapy alone. An updated overall survival analysis based on an additional year of follow-up showed a 25% improvement among Herceptin-treated patients.
Herceptin has previously been approved in a number of countries for the treatment of early-stage Her2-positive breast cancer in combination with specific chemotherapy regimens. It has also been approved as monotherapy against early-stage Her2-positive breast cancer after multiple other treatment regimens have been carried out. The humanized mAb has separately been cleared for the first-line treatment of metastatic Her2-positive breast cancer in combination with paclitaxel, and as monotherapy for treating metastatic disease in patients who have previously received one or more types of chemotherapy.
Genentech and parent company Roche are separately developing an antibody-drug conjugate (ADC), trastuzumab-DM1 (T-DM1), for the treatment of breast cancer. The ADC is composed of Herceptin with the cytotoxic agent DM1. In July the firms filed a BLA for accelerated approval of T-DM1 in the treatment of patients with advanced Her2-positive breast cancer whose disease continues to progress despite previous treatment using multiple Her2-targeted medicines and chemotherapies.
In August, however, they received a Refuse to File letter from the FDA. It stated that the trial on which the application was based did not meet the standard for accelerated approval because all available treatment choices approved for metastatic breast cancer, regardless of Her2 status, had not been exhausted in the study population. The application was based on data from a single-arm Phase II trial demonstrating that T-DM1 therapy shrank tumors in one-third of women, who had received an average of seven prior medicines including two Her2-targeted therapies.
Genentech plans on submiting data from a Phase III randomized study (EMILIA) to support a new T-DM1 BLA in mid-2012. The EMILIA study compares T-DM1 to lapatinib in combination with capecitabine in people with advanced Her2-positive breast cancer whose disease has worsened after receiving initial treatment.
Roche says that, in addition, several Phase II and III trials of T–DM1 either alone or in combination with other medicines are planned or ongoing.
Roche reported global sales of Herceptin of SwFr 2.8 billion (about $2.9 billion) in the first half of 2010, up 8% on the same period in 2009.