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Understanding HER2's Role in Gastric/GEJ Cancer

Insights From: David Ilson, MD PhD, Memorial Sloan Kettering Cancer Center; Minaxi Jhawer, MD, Englewood Hospital and Medical Center
Published: Monday, Aug 06, 2018



Transcript: 

Minaxi Jhawer, MD: HER2 is one of the well-validated biomarkers in patients with gastric cancer. It’s well known in breast cancer, but this is very different from breast cancer, so that’s something that we need to all be aware of. The immunohistochemistry 3+ patients, or patients who are 2+ for HER2 but are clearly amplified by FISH [fluorescence in situ hybridization], are the ones whom we consider positive. Based on the ToGA trial, we saw that patients run around a 10% to 23% chance of being HER2-positive. The tumors that are more proximal, that are more moderately differentiated versus poorly differentiated, and that tend to be intestinal in the Lauren classification, tend to be more HER2 expressive. The ToGA trial showed us that patients who got combination chemotherapy, cisplatin/5-FU [fluorouracil] with trastuzumab, had an improvement in their overall survival. So that became a standard of care in patients who have HER2-positive gastric cancer. They should be given trastuzumab.

Whether you should continue it in second line and beyond is not well known. In fact, there are no compelling studies that show you would want to continue them through it. But that’s probably still evolving. In addition, there have been similar studies in breast cancer looking at lapatinib and pertuzumab seeing whether we can get a better response in patients who are HER2-positive, but we don’t see that unfortunately. It probably has a different biology than breast cancer, but it’s something that we have a strong targeted drug available for. For now, that’s only trastuzumab.

David Ilson, MD, PhD: As we said earlier, the key molecular testing for metastatic esophagogastric cancer is HER2, and perhaps later-line MSI [microsatellite instability] and PD-L1 testing. But about 20% of gastric cancers will be HER2-positive and about 30% of esophagus and GE [gastroesophageal] junction cancers. We would do immunohistochemistry staining as the first test. If they’re strongly HER2-expressing, 3+, they’re declared positive. Equivocal is 2+ with FISH testing. If they’re FISH-positive, then we consider them HER2-positive. If they’re immunohistochemistry 0 to 1+, we declare them negative and don’t do FISH testing. We don’t typically do FISH testing alone.

The subset analysis from the randomized trial of trastuzumab shows that if a patient were only FISH-positive and HER2 immunohistochemistry–negative, they don’t tend to benefit from trastuzumab. First line, we would combine fluorinated pyrimidine and a platinum drug with trastuzumab, although the regimen used in the trial was either capecitabine/cisplatin or 5-day infusion 5-FU with platinum, with trastuzumab every 3 weeks. Nobody uses this. We use FOLFOX [oxaliplatin/fluorouracil/folinic acid] with trastuzumab cycled every 2 weeks as the preferred dose and schedule.

Transcript Edited for Clarity 
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Transcript: 

Minaxi Jhawer, MD: HER2 is one of the well-validated biomarkers in patients with gastric cancer. It’s well known in breast cancer, but this is very different from breast cancer, so that’s something that we need to all be aware of. The immunohistochemistry 3+ patients, or patients who are 2+ for HER2 but are clearly amplified by FISH [fluorescence in situ hybridization], are the ones whom we consider positive. Based on the ToGA trial, we saw that patients run around a 10% to 23% chance of being HER2-positive. The tumors that are more proximal, that are more moderately differentiated versus poorly differentiated, and that tend to be intestinal in the Lauren classification, tend to be more HER2 expressive. The ToGA trial showed us that patients who got combination chemotherapy, cisplatin/5-FU [fluorouracil] with trastuzumab, had an improvement in their overall survival. So that became a standard of care in patients who have HER2-positive gastric cancer. They should be given trastuzumab.

Whether you should continue it in second line and beyond is not well known. In fact, there are no compelling studies that show you would want to continue them through it. But that’s probably still evolving. In addition, there have been similar studies in breast cancer looking at lapatinib and pertuzumab seeing whether we can get a better response in patients who are HER2-positive, but we don’t see that unfortunately. It probably has a different biology than breast cancer, but it’s something that we have a strong targeted drug available for. For now, that’s only trastuzumab.

David Ilson, MD, PhD: As we said earlier, the key molecular testing for metastatic esophagogastric cancer is HER2, and perhaps later-line MSI [microsatellite instability] and PD-L1 testing. But about 20% of gastric cancers will be HER2-positive and about 30% of esophagus and GE [gastroesophageal] junction cancers. We would do immunohistochemistry staining as the first test. If they’re strongly HER2-expressing, 3+, they’re declared positive. Equivocal is 2+ with FISH testing. If they’re FISH-positive, then we consider them HER2-positive. If they’re immunohistochemistry 0 to 1+, we declare them negative and don’t do FISH testing. We don’t typically do FISH testing alone.

The subset analysis from the randomized trial of trastuzumab shows that if a patient were only FISH-positive and HER2 immunohistochemistry–negative, they don’t tend to benefit from trastuzumab. First line, we would combine fluorinated pyrimidine and a platinum drug with trastuzumab, although the regimen used in the trial was either capecitabine/cisplatin or 5-day infusion 5-FU with platinum, with trastuzumab every 3 weeks. Nobody uses this. We use FOLFOX [oxaliplatin/fluorouracil/folinic acid] with trastuzumab cycled every 2 weeks as the preferred dose and schedule.

Transcript Edited for Clarity 
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