On September 20, Chugai Pharmaceutical (Roche) obtained approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) for HER2-positive inoperable or recurrent breast cancer (rBC), for the HER2 targeted antibody (Ab)-drug conjugate, Kadcyla intravenous (IV) infusion 100 and 160mg (trastuzumab emtansine [T-DM1; genetical recombination]). The approval triggers a US$5mn payment to ImmunoGen.
In January 2013, Chugai filed an NDA for approval for HER2-positive inoperable or rBC based on results from a Japanese Phase II trial and a global Phase III trial (EMILIA). This approval was obtained based on data from these trials. EMILIA is an international Phase III study comparing Kadcyla alone with Tykerb (lapatinib) in combination with Xeloda (capecitabine) in patients with HER2-positive metastatic or unresectable locally advanced BC who had previously been treated with Herceptin (trastuzumab) and a taxane. Patients from Japan were not included in this trial.
Progression-free survival (PFS) was one of its primary endpoints, and patients who received Kadcyla experienced a 35% reduction in the risk of disease progression or death compared with those who received Tykerb plus Xeloda. The median PFS improved by 3.2 months from 6.4 months on Tykerb and Xeloda to 9.6 months on Kadcyla (hazard ratio [HR]=0.65; p<0.0001).
As for overall survival (OS), another primary endpoint, the risk of death was reduced by 32% for patients who received Kadcyla compared with those who received Tykerb plus Xeloda. Patients in the study treated with Kadcyla survived a median time of 5.8 months longer than those who received Tykerb and Xeloda (median OS: 30.9 vs 25.1 months; HR=0.68; p=0.0006).
Regarding safety, 40.8% of the patients who received Kadcyla and 57.0% of the patients who received Tykerb plus Xeloda experienced Grade 3 or higher adverse events (AEs). The most common Grade 3 or higher AEs reported in patients receiving Kadcyla, compared with those receiving Tykerb plus Xeloda, included low platelet count and increase of AST and ALT levels.
The Phase II trial conducted in Japan confirmed the efficacy and the tolerability of Kadcyla in Japanese patients with HER2-positive metastatic or unresectable locally advanced BC.
Kadcyla comprises of the anit-HER2 humanised monoclonal Ab, trastuzumab, and a chemotherapeutic drug, DM1, attached together using a stable linker. Kadcyla is designed to target HER2, inhibit HER2 signalling, induce Ab-dependent cell mediated cytotoxicity, and deliver the chemotherapeutic drug DM1 directly inside HER2-positive cancer cells. Once Kadcyla is taken up by those cancer cells, it is designed to destroy them by the DM1.
Kadcyla was approved for patients with previously treated, HER2-positive metastatic BC in the US in February and an MAA has been submitted to the EMA by Roche.