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The HER2 Pathway in GI Cancer
Andrea Sartore Bianchi, MD, Grande Ospedale Metropolitano Niguarda and Università degli Studi di Milano, Italy, discusses the HER2 Pathway in gastrointestinal cancer at the 2019 ESMO World Congress on Gastrointestinal Cancer.
Dr. Andrea Sartore Bianchi: Hello, my name is Andrea Sartore Bianchi. I'm medical oncologist at the Niguarda Ca' Granda Hospital in Milano and University of Milano. I will talk to you about HER2 in gastrointestinal cancer.
Speaking about gastrointestinal cancer, we know that HER2 is already an established target in gastric cancer. We have a validated treatment in gastric cancer with trastuzumab and chemotherapy in first line, based on positive results of the ToGA study.
Now we have data about other histologies among GI tumors. In colorectal cancer, for example, we know that HER2 is altered, either mutated or amplified, in about five percent of tumors. Amplification is likely more prevalent. I would say three percent of amplification and two percent of mutation. There is an enrichment in tumors that are KRAS wild-type.
Now we have also a clinical rationale for identifying HER2 as a target in colorectal cancer. Based on the data in pre-clinical PDX models of efficacy of the combination of trastuzumab and lapatinib, it was launched a few years ago, the HERACLES initiative in Italy.
In the HERACLES trial, we demonstrated that the combination of trastuzumab and lapatinib is effective in HER2-amplified KRAS wild-type tumors. Now we have some new data. The CRC cohort of the MyPathway study, conducted in the US, provided also positive results with the combination of pertuzumab and trastuzumab.
It's based on the HERACLES data and also on the MyPathway data that now the HER2-targeted treatment with trastuzumab, plus either lapatinib or pertuzumab, is in the more updated version of NCCN Guidelines for colorectal cancer.
It's important to test colorectal cancer for HER2 because this is a potential target for treatment with HER2-targeted treatment. The studies are ongoing also testing HER2-targeted treatment in other settings, in other histologies.
Also in colorectal cancer, there are studies ongoing, evaluating if it's possible to enhance the therapeutic effect of a HER2-targeted treatment. For example, there is a trial ongoing with tucatinib and trastuzumab. Also, newer agents targeting HER2, like DS-8201, are ongoing also in colorectal cancer, together with other strategies with more innovative immunotherapies.
Now Speaking about other histologies, we have that in biliary tract cancer you can find HER2 amplification in percentage as high as 10 to 15 percent of patients. Also in this tumor, we have positive data with the combination of pertuzumab and trastuzumab in the biliary tract cohort of the MyPathway studies. I think that also in this histology, we have a strong rationale for pursuing research with this targeted treatment.
In conclusion, we have data of the value of HER2 as a biomarker and as a target for treatment in GI tumors. Especially, we have, of course data for gastric cancer as for amplification, but now emerging data for colorectal cancer and biliary tract cancer.
As for mutation, though, we have data indicating there is a tissue dependency on the response to HER2 treatment. Therefore, as for mutation, I think we need some more mature data with combination [therapy] possibly rather than monotherapy.
