Re-evaluation of HER2 status in patients with HER2-positive advanced or recurrent gastric cancer refractory to trastuzumab (KSCC1604)

Saeki, Hiroshi; Oki, Eiji; Kashiwada, Tomomi; Arigami, Takaaki; Makiyama, Akitaka; Iwatsuki, Masaaki; Narita, Yuji; Satake, Hironaga; Matsuda, Yoshiko; Sonoda, Hideto; Shimokawa, Mototsugu; Maehara, Yoshihiko

doi:10.1016/j.ejca.2018.09.024

Cited by 66 publications

(60 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we demonstrated that in three out of seven patients (42.9%), HER2-positive tumor cells in resected specimens disappeared after trastuzumab-based chemotherapy. To date, several investigators have reported the loss of HER2 positivity in 29%-61% of biopsied tumors and 21%-42% of surgical specimens obtained from patients with gastric cancer, after trastuzumab-based chemotherapy (16)(17)(18)(19)(20). Consequently, these results are consistent with our findings showing loss of HER2 positivity (42.9%).…”

Section: Discussionsupporting

confidence: 92%

“…The third key issue is the effect of formalin fixation conditions. Saeki et al reported that the use of fixatives other than 10% neutral buffered-formalin significantly reduce the HER2 overexpression rate (18). In the present study, neutral buffered-formalin at 10% and 20% was used for HER2 IHC in six and one out of seven patients, respectively.…”

Section: Discussionmentioning

confidence: 65%

See 1 more Smart Citation

Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background/Aim: The aim of the present study was to compare human epidermal growth factor receptor 2 (HER2) expression before and after trastuzumab-based chemotherapy in patients with advanced HER2-positive gastric cancer. Materials and Methods: We assessed HER2 expression using immunohistochemistry and/or fluorescence in situ hybridization in pre-treatment biopsied specimens and post-treatment resected specimens obtained from seven patients with advanced HER2-positive gastric cancer receiving trastuzumab-based chemotherapy. Results: Four patients maintained the HER2-positive status and three patients had a change in HER2 expression from positive to negative. In patients showing the loss of HER2 expression after treatments, HER2-positive tumor cells with a dominant histological type disappeared, and HER2-negative tumor cells with another dominant histological type were identified. Conclusion: HER2 expression can change after trastuzumabbased chemotherapy in patients with advanced HER2positive gastric cancer. Continuous monitoring of HER2 expression after treatments may be utilized to determine whether the continued use of trastuzumab is advisable.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 65%

Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Studies that evaluated changes in HER2 protein expression in AGC patients receiving trastuzumab-containing regimens by comparison of matched pre-and post-treatment samples have demonstrated a loss of HER2 [33,34]. In the aforementioned T-ACT study [21], given that collection of new tumor biopsy samples at the time of study enrollment (after progression on prior trastuzumab therapy) was not mandatory, reassessment of HER2 positivity was performed for only 16 out of 44 patients.…”

Section: Loss Of Her2 Protein Expressionmentioning

confidence: 99%

Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Mitani

Kawakami

2020

Cancers

View full text Add to dashboard Cite

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody-drug conjugates that are under development and have shown promising antitumor activity in early studies. basis of these results, trastuzumab was approved for AGC with a high HER2 expression level, and trastuzumab-containing regimens are now a standard option for the first-line treatment of such patients, who accounted for 7% to 17% of all individuals with gastric cancer [3-5]. Derivatives of the ToGA Regimen in the First-Line SettingThe ToGA trial adopted a regimen of cisplatin combined with either 5-fluorouracil (5-FU) or capecitabine, whereas subsequent prospective studies found similar treatment outcomes with regimens containing oxaliplatin or tegafur-gimeracil-oteracil (S-1). In a single-arm, nonrandomized phase II trial (HER2-based strategy in stomach cancer (HERBIS)-1) performed in Japan [6], trastuzumab in combination with S-1 plus cisplatin yielded a confirmed ORR of 68%, with a median OS and a median PFS of 16.0 and 7.8 months, respectively, in HER2-positive AGC patients with measurable lesions, with these results being similar to those of the ToGA trial [2]. Similar efficacy was also apparent in AGC patients without measurable lesions (HERBIS-1B study) [7]. Three phase II studies that assessed the combination of trastuzumab with capecitabine plus oxaliplatin reported a median OS, a median PFS, and an ORR of 13.8 to 21.0 months, 7.1 to 9.8 months, and 46.7% to 67.3%, respectively [8][9][10]. Trastuzumab in combination with S-1 plus oxaliplatin was also shown to provide a similar treatment outcome in a phase II study, with a median OS, a median PFS, and an ORR of 18.1 months, 8.8 months, and 70.7%, respectively [11]. A meta-analysis of data from these trials revealed that S-1 or oxaliplatin can substitute effectively for capecitabine or 5-FU or for cisplatin, respectively [12].Immune checkpoint inhibitors such as antibodies to programmed cell death-1 (PD-1) have recently revolutionized treatment strategies for advanced cancer. Given that trastuzumab was found to stimulate T cell responses [13], the combination of trastuzumab-containing regimens with antibodies to PD-1 is receiving attention. A phase II study including 37 patients with HER2-positive AGC treated in the first-line setting with capecitabine, oxaliplatin, and trastuzumab in combination with the anti-PD-1 antibody pembrolizumab reported an ORR of 83%, with a median PFS of 11.4 months and a median ...

show abstract

“…Results of a phase II study comparing the combination of paclitaxel with beyond progression trastuzumab versus paclitaxel alone in Her2 positive patients, who already received first line antibody/chemotherapy combination therapy, showed that there was no benefit of combination therapy concerning the overall survival (9.95 months with paclitaxel versus 10.2 months in the paclitaxel + trastuzumab arm; HR = 1.23; 95% CI 0.75-1.99; p = 0.20) [64]. It is surmised that this effect might be due to the loss of HER2 after first line treatment, since almost 2/3 of patients lost their Her2 positivity, which was evaluated in an additional biopsy at the time of progression under trastuzumab [64,65]. However, some new retrospective analyses suggest that although there is no improvement of the OS, patients might still have a clinical benefit from the continuation of Trastuzumab beyond first-line progression [66,67].…”

Section: Her2 Positive Gastroesophageal Tumoursmentioning

confidence: 99%

New Treatment Options for Advanced Gastroesophageal Tumours: Mature for the Current Practice?

Puhr

Preusser

Prager

2020

Cancers

View full text Add to dashboard Cite

Several clinical trials attempted to identify novel treatment options for advanced gastroesophageal tumours in first, second and further lines. Although results of targeted therapy regimens were mainly disappointing, novel immunotherapy agents showed promising activity, which led to their approval in second and third lines in many countries. This review focuses on the results of recent clinical trials investigating novel agents including targeted therapies, immunotherapy components and chemotherapies and discuss their current impact as well as current approval status on the treatment armamentarium of advanced gastroesophageal tumours.

show abstract

Re-evaluation of HER2 status in patients with HER2-positive advanced or recurrent gastric cancer refractory to trastuzumab (KSCC1604)

Cited by 66 publications

References 24 publications

Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer

Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer

Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

New Treatment Options for Advanced Gastroesophageal Tumours: Mature for the Current Practice?

Contact Info

Product

Resources

About