Choosing Second-Line Therapy for HER2+ Gastric Cancer


Bassel El-Rayes, MD, discusses how he approaches second-line therapy for patients with HER2-positive gastric cancer.

Bassel El-Rayes, MD, director of the division of hematology and oncology, vice chair of clinical research, and professor of hematology and medical oncology at the University of Alabama at Birmingham, discusses how he approaches second-line therapy for patients with HER2-positive gastric cancer.

According to El-Rayes, the choice of second-line therapy for gastric cancer depends on the first-line therapy given, as well as whether the patient is HER2-positive. Other considerations include performance status, organ function, and other patient characteristics.

If a patient is HER2-positive, El-Rayes would use trastuzumab (Herceptin) plus a platinum-based agent such as cisplatin, 5FU [fluorouracil], or FOLFOX [leucovorin calcium, fluorouracil, and oxaliplatin] as frontline therapy. Following progression, the antibody-drug conjugate trastuzumab deruxtecan (Enhertu) may be given in the second line for patients who have previously received trastuzumab.

El-Rayes says trastuzumab deruxtecan may offer advantages in disease control and survival over second-line chemotherapy options due to being an HER2-targeted agent. In the DESTINY-Gastric01 study (NCT03329690), it demonstrated improved efficacy and median overall survival benefit of 12.5 versus 8.4 months for physician’s choice of irinotecan or paclitaxel chemotherapy for patients with HER2-positive advanced gastric cancer.


0:08 | The things that affect the second-line therapy in patients with gastric cancer that are HER2-positive, as of course the choice of therapy in the front line, and the overall medical condition of the patient performance status, organ function, things of that nature.

0:29 | In my practice, when I approach patients with gastric cancer, one of the first things I look at is if they are HER2-positive. If they are HER2-positive, then [in the] frontline setting, I'm using trastuzumab plus a platinum-based tablet, like cisplatin, 5FU, or FOLFOX, or something of that nature. At the time of progression, I'm usually shifting over to trastuzumab deruxtecan, rather than going to another second-line chemotherapy like [paclitaxel] or ramicirumab. I feel like targeting the HER2 in the second-line setting provides advantage in terms of disease control and survivorship.

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