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

Abstract

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.

Phase II Study of Continued Trastuzumab Plus Irinotecan in Patients with HER2-positive Gastric Cancer Previously Treated with Trastuzumab (HGCSG 1201)

“…Al-Shamsi et al suggested that the continuation of trastuzumab beyond disease progression in patients with HER2-positive metastatic gastric cancer was feasible and safe in their retrospective analysis. 4 These findings coincided with the absence of cardiac events and other major adverse events (AEs) in our study population.…”

Tailoring second-line or above therapy for patients with advanced or metastatic gastric cancer: A multicenter real-world study

“…Based on the results of phase 3 ToGA study, trastuzumab combined with chemotherapy has become the standard treatment option for human epidermal growth factor receptor-2 (HER2) positive metastatic gastric cancer ( Bang et al, 2010 ). However, the positive rate of HER-2 in Chinese patients is only 12–13%, and simultaneously the value of continuous use of trastuzumab beyond progression (TBP) as second-line therapy is still controversial ( Al-Shamsi et al, 2016 ; Ter Veer et al, 2018 ). Until now, the approved anti-angiogenic drugs for metastatic gastric cancer include ramucirumab and apatinib.…”

Daily practices in chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma: METESTOMAC French prospective cohort

“… 26 , 27 Platinum and taxanes were used in 18% and 14% of cases, respectively, as in the Russian cohort (19% and 14%), and more often than in the South Korean cohort (13% and 8%). 26 , 27 Trastuzumab was continued as the second line in 28.6% of patients who had it in the first line, even though this was outside the marketing authorization: a randomised phase‐2 study showed the lack of benefit of continuing trastuzumab in the second line after failure of a first line combining 5FU, platinum and trastuzumab, 25 while retrospective series suggest that maintaining HER2 blockade is feasible 32 , 33 and would lead to increased survival.…”