First- and Second-Line Treatment Options for HER2+ Gastric Cancer


A broad overview of the treatment armamentarium for patients receiving first- or second-line therapy for HER2+ gastric cancer.


Sarah Donahue, MPH, NP, AOCNP: What are the front-line treatment options for patients with HER2-positive gastric cancer? Liz, do you know? I think we went over this earlier. Do you mind going over it again with us?

Elizabeth Prechtel Dunphy, DNP, CRNP, AOCN: Yes. Per the NCCN [National Comprehensive Cancer Network] guidelines, a fluoropyrimidine, such as fluorouracil, and capecitabine with oxaliplatin and trastuzumab. FOLFOX [folinic acid, fluorouracil, and oxaliplatin] or CAPOX [capecitabine and oxaliplatin] with trastuzumab or fluoropyrimidine, again, the 5-FU [fluorouracil] or capecitabine, with cisplatin and trastuzumab. And with both of those, depending on their PD-L1 status, pembrolizumab could be added.

Other regimens that could be considered are fluorouracil and irinotecan. Paclitaxel, with or without cisplatin, or in combination with carboplatin. Docetaxel, with or without cisplatin. 5-FU or capecitabine alone. Docetaxel, cisplatin, or oxaliplatin and fluorouracil, or docetaxel, carboplatin and fluorouracil. The last ones, from fluorouracil with irinotecan, are other recommended regimens. The primary regimens usually recommended are FOLFOX or CAPOX with trastuzumab, or fluorouracil with cisplatin or trastuzumab, plus or minus pembrolizumab.

Sarah Donahue, MPH, NP, AOCNP: After progression on that first-line regimen, whichever one is chosen, what is the recommended treatment approach in a second-line setting, and what are the data available to support it?

Elizabeth Prechtel Dunphy, DNP, CRNP, AOCN: As Theresa mentioned earlier, treatment for our patients with gastric cancer depends on their prior therapies, performance status, and their comorbidities. The NCCN preferred regimens are: ramucirumab and paclitaxel, trastuzumab deruxtecan, docetaxel, single-agent paclitaxel, single-agent irinotecan, single-agent combination of fluorouracil and irinotecan. And then possibly in the third line, Lonsurf, or trifluridine and tipiracil, which is an oral agent.

Some of the data that can be provided for the second-line therapy particular to trastuzumab deruxtecan come from the DESTINY-Gastric01 study, where 187 patients were treated. Approximately 125 of the patients received trastuzumab deruxtecan and 62 were on a physician’s choice chemotherapy, and that was either irinotecan or paclitaxel. The breakdown was 55 patients had irinotecan and 7 had paclitaxel. The overall survival was 12.5 vs 8.9 months in the trastuzumab deruxtecan arm compared to the physician’s choice chemotherapy arm. The overall responses were 51.3% vs 14.3%, respectively. Disease-control rate was also improved in the trastuzumab deruxtecan arm, being 85.7% vs 62.5%. And the duration of response was also improved, with the trastuzumab deruxtecan arm being 12.5 vs 3.9 months. The median progression-free survival was 5.6 vs 3.5 months. So, each of those end points was improved in the patients who were on the trastuzumab deruxtecan arm of the study.

Transcript edited for clarity.

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