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Phase II study of the effectiveness and safety of trastuzumab and paclitaxel for taxane- and trastuzumab-naïve patients with HER2-positive, previously treated, advanced or recurrent gastric cancer (JFMC45-1102)

Nishikawa K, Takahashi T, Takaishi H, Miki A, Noshiro H, Yoshikawa T, et al.

Int J Cancer 2016 Aug 13. [Epub ahead of print]

Professor David Cunningham’s Editorial Comment

In this study, Japanese investigators examined the efficacy of 2nd line trastuzumab plus paclitaxel in gastric cancer patients with HER2 positive tumours. Of note, although patients had received prior chemotherapy, they were trastuzumab naïve. The objective radiological response rate was 37% and progression free and overall survival in this trial were survival were 5.1 (95% CI 3.8–6.5) and 17.1 (95% CI 13.5–18.6) months, respectively. These results are encouraging but there are several important caveats which must be considered.

Firstly, as patients were not previously treated with trastuzumab these results cannot be extrapolated to patients who have been treated with trastuzumab in first line chemotherapy and have developed acquired resistance. In particular, it is not possible to compare these results with the GATSBY trial (taxane vs TDM1, Kang ASCO GI 2016) as most (77%) patients in that study had previously received trastuzumab.

Secondly, as patients in this trial have an oncogenic addiction to HER2 signalling and are treated with an anti-HER2 targeted agent the results cannot  be compared directly with second line paclitaxel chemotherapy in non-HER2 addicted patients.    Therefore although these results are very good this trial population does not exist in routine clinical practice.

For patients with HER2 positive breast cancer, second and third line chemotherapy plus anti-HER2 directed treatment results in significant overall survival benefits, however, this is not the case for patients with HER2 positive oesophagogastric cancer. There are several potential reasons for this including heterogeneity of HER2 expression and relative short median overall survival due to disease related morbidity. More research is needed in order to exploit the HER2 axis for patients with oesophagastric cancer in order to improve survival for these patients. For now, the only evidence based HER2 directed treatment remains trastuzumab in combination with platinum/fluoropyrimidine based chemotherapy in the first line setting.


Paclitaxel is a standard second-line gastric cancer treatment in Japan. Trastuzumab could be active as second-line chemotherapy for taxane/trastuzumab-naïve patients with epidermal growth factor 2 (HER2)-positive advanced gastric cancer. Patients aged ≥20 years with HER2-positive, previously treated (except for trastuzumab and taxane), unresectable or recurrent gastric adenocarcinoma underwent combined trastuzumab (first and subsequent doses of 8 and 6 mg/kg, respectively, every 3 weeks) and paclitaxel (days 1, 8, 15, every 4 weeks) treatment. Study endpoints were best overall response, progression-free survival, overall survival, and safety. From September 2011 to March 2012, 47 Japanese patients were enrolled. Forty patients discontinued treatment after a median of 128.5 (range 4-486) days. Complete and partial responses were obtained in one and 16 patients (response rate of 37% [95% CI 23-52]), respectively. Median progression-free survival and overall survival were 5.1 (95% CI 3.8-6.5) and 17.1 (95% CI 13.5-18.6) months, respectively. Grade 3/4 adverse events were neutropenia (32.6%), leukopenia (17.4%), anemia (15.2%), and hypoalbuminemia (8.7%). There was no clinically significant cardiotoxicity or cumulative toxicity. Three (disturbed consciousness, pulmonary fibrosis, and rapid disease progression) grade 5 events occurred. In conclusion, trastuzumab combined with paclitaxel was well tolerated and was a promising regimen for patients with HER2-positive, previously treated, advanced or recurrent gastric cancer. This article is protected by copyright.

All rights reserved © 2016 UICC.

KEYWORDS: Human epidermal growth factor receptor; Paclitaxel; Recurrence; Stomach neoplasms; Trastuzumab

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