Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience.

Al-Shamsi HO, Fahmawi Y, Dahbour I, Tabash A, Rogers JE, Mares JE, Blum MA, Estrella J, Matamoros A Jr, Sagebiel T, Devine CE, Badgwell BD, Lin QD, Das P, Ajani JA.
J Gastrointest Oncol. 2016 Aug;7(4):499-505. doi: 10.21037/jgo.2016.06.16.


Background: Despite the wide spread use of trastuzumab in human epidermal growth factor receptor 2
(HER2) overexpressing metastatic gastric cancer patients, its optimal duration of administration beyond
first-line disease progression is unknown. In HER2 overexpressing metastatic breast cancer, trastuzumab
continuation beyond first-line disease progression has shown improvement in time to progression (TTP)
without an increased risk of treatment related toxicity.

Methods: HER2-overexpressing metastatic gastric cancer patients were identified from our database
between January 2010 and December 2014. We retrospectively reviewed the medical records of 43 patients who received trastuzumab in combination with chemotherapy as first-line and continued trastuzumab beyond disease progression.

Results: Forty-three cases were identified, 27 males (62.8%), median age of the patients was 58 years.
Thirty-five (81.4%) presented with stage 4 as their initial presentation. Eighty one percent had 3+ HER2
overexpression by immunohistochemistry (IHC) and 18% had 2+ HER2 overexpression confirmed by fluorescence in situ hybridization (FISH). Thirteen (52%) were moderately differentiated, 16 (37.1%) were
poorly differentiated. The most common sites of metastasis were liver 35 (81.4%) and lung 14 (32.5%). The
most commonly used first-line regimen was oxaliplatin, 5-fluorouracil (5-FU), and trastuzumab in 22 (51.1%) patients. Twenty-five (58.1%) patients received irinotecan, 5-FU and trastuzumab in the second-line. Progression-free survival (PFS) was 5 months (95% CI: 4.01–5.99 months). Five patients are still alive and excluded from calculating the median overall survival (OS) which was 11 months (range, 5–53 months) for the remaining 20 subjects of this second-line group. Trastuzumab was not discontinued due to side effects in any of the study population.

Conclusions: In conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in patients with HER2-overexpressing metastatic gastric cancer is feasible and safe. Randomized studies are warranted.

Keywords: Gastric cancer; human epidermal growth factor receptor 2 (HER2); trastuzumab

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