Summary
Many adenocarcinomas and sqamous cell cancers express HER2 . However, HER2 based therapy is only approved therapy in early and late stage breast cancer. 25% of gastric cancers express HER2. The Toga trial was conducted practically everywhere except the US; indeed there are geographic differences in gastric cancer in regards to risks, location, age of diagnosis, stage at presention, etc.. which are notable. However, the trial appears well powered between arms. The ToGA trial used a somewhat outdated regimen as control (5FU +CDDDP) however for study purposes that was appropriate. Other regimens will be compared to the H+chemo arm across studies (TPF, regimens investigated in REAL, etc..). I would assume minimal toxicity was added with H (aside from cardiac). Although we should all be optimistic (gastric cancer has a 5 yr median survival of 10-15%; incidence of proximal gastric and GE cancer is increasing more than any other cancer) results will need to be scrutinized when available.
Analysis
Roche/Genentech will proceed with regulatory approval for Herceptin in advanced gastric cancer and will wait Phase II data on lapitinib (with or without Taxol) as well as the bevacizumab data (also in phase phase 3 trial). Next order...data dissemination (ASCO '09), etc.. They are of course well positioned in the market and signifcantly ahead of competitors (except makers of Anti-EGFR therapy. Moving this drug or other active compounds into the adjuvant setting is appropriate. However, the design, inclusions, surgical/radiation mandates, regimen chosen as control (CDDP and 5FU maybe outdated although that is still the standard based on the intergroup trial 0116) need careful consideration.
