Efficacy and safety of trastuzumab (T-mab) and paclitaxel for T-mab naïve patients with HER2 positive previously treated metastatic gastric cancer (JFMC45-1102).

63 Background: The global, randomized, Phase III ToGA study showed that the first-line treatment of trastuzumab (T-mab) combined with capecitabine and cisplatin a survival (OS) benefit for patients (pts) with HER2-positive metastatic gastric cancer (mGC). However, there is no report concerning about the efficacy and safety of T-mab containing second-line treatment for T-mab naïve patients with HER2-positive mGC. Therefore, we planned a phase II study of paclitaxel plus trastuzumab in this setting. Methods: JFMC45-1102 is multicentre Phase II study. Patient (pts) with HER2 positive (IHC3+ or IHC2+/FISH+), histologically confirmed gastric adenocarcinoma, age≥20, received one or more prior chemotherapy but no prior therapy with T-mab, normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Pts received paclitaxel (80 mg/m2on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg for the initial dose, followed by 6 mg/kg q3w) until disease progression, unacceptable toxicity or patient’s refusal. The primary endpoint was overall response rate evaluated according to RECIST ver1.0 (ORR; Threshold and expected ORR would be 15% and 30%), and the secondary endpoints include progression free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. A LVEF assessment was repeated every three months. Results: Between November 2011 to March 2012, 45 pts were enrolled. Pts characteristics were: gender (M/F); 36/9, median age; 69, ECOG PS0/1/2; 34/10/1, advanced/recurrence; 25/20, number of prior treatment (1/2): 40/5. At 16 weeks, 43 pts were ORR and disease control rate (CR+PR+SD) were 37.2% (95% CI; 23.0%-53.3%) and 83.7%(95% CI; 69.3%-93.2%), respectively. The LVEF assessment was performed in 31 patients. More than 10% decrease in LVEF was observed in only one patient, although total incidence of decrease in LVEF was 56% (17/31 pts). Conclusions: Combination chemotherapy of paclitaxel plus trastuzumab is generally well tolerated and showed promising activity for T-mab native patients with HER2-positive previously treated advanced or recurrent gastric cancer. Clinical trial information: UMIN000006223.

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Efficacy and safety result of trastuzumab (T-mab) and paclitaxel for T-mab naive patients with HER2-positive previously treated advanced or recurrent gastric cancer (JFMC45-1102): Final report.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.79 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 79-79 ◽

Cited By ~ 2

Author(s):

Tsunehiro Takahashi ◽

Kazuhiro Nishikawa ◽

Akira Miki ◽

Hirokazu Noshiro ◽

Takaki Yoshikawa ◽

...

Keyword(s):

Gastric Cancer ◽

Phase Ii ◽

Primary Endpoint ◽

Phase Ii Study ◽

Left Ventricular Ejection ◽

Line Treatment ◽

Efficacy And Safety ◽

Her2 Positive ◽

Recurrent Gastric Cancer ◽

Previously Treated

79 Background: The global, randomized, phase III ToGA study showed that the first-line treatment of trastuzumab (T-mab) combined with capecitabine and cisplatin a survival (OS) benefit for patients (pts) with HER2 positive advanced or recurrent gastric cancer. However, there is no report concerning about the efficacy and safety of T-mab containing second-line treatment for T-mab naïve pts with HER2 positive advanced or recurrent gastric cancer. Therefore, we planned a phase II study of paclitaxel plus T-mab in this setting. Methods: JFMC45-1102 is multicentre phase II study. Pts with HER2 positive (IHC3+ or IHC2+/FISH+), histologically confirmed gastric adenocarcinoma, age ≥ 20, received one or more prior chemotherapy but no prior therapy with T-mab, normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Pts received paclitaxel (80 mg/m2 on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg for the initial dose, followed by 6 mg/kg q3w) until disease progression, unacceptable toxicity or patient’s refusal. The primary endpoint was overall response rate (ORR), and the secondary endpoints include progression free survival (PFS), time to treatment failure (TTF), OS and safety. Results: A total of 47 pts were enrolled from September 2011 to March 2012.The primary endpoint ORR was 37.0% (95%CI, 23 to 52).Complete response was observed in 1 case (2.2%).The PFS data was matured, and the median PFS was 5.09 months (95%CI, 3.79 to 6.49), TTF 5.09 months (95%CI, 3.72 to 6.49), OS 16.81 months (95%CI, 13.54 to 18.65). One patient died of lung pulmonary fibrosis during therapy. The most common grade 3-4 adverse events were leucopenia (17.4%), neutropenia (32.6%), anemia (15.2%). Conclusions: Combination chemotherapy of paclitaxel plus T-mab is generally well tolerated and showed promising activity for T-mab naïve patients with HER2 positive previously treated advanced or recurrent gastric cancer. Clinical trial information: UMIN000006223.

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Multicenter, phase II study of trastuzumab and paclitaxel to treat HER2-positive, metastatic gastric cancer patients naive to trastuzumab (JFMC45-1102).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4096 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4096-4096 ◽

Cited By ~ 2

Author(s):

Satoru Iwasa ◽

Kazuhiro Nishikawa ◽

Akira Miki ◽

Hirokazu Noshiro ◽

Akira Tsuburaya ◽

...

Keyword(s):

Gastric Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Metastatic Gastric Cancer ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Line Treatment ◽

Her2 Positive ◽

Ventricular Ejection Fraction ◽

Multicenter Phase

4096 Background: The ToGA study indicated that first-line treatment using trastuzumab (T-mab) combined with capecitabine and cisplatin conferred a survival (OS) benefit to patients with HER2-positive metastatic gastric cancer (mGC). However, no reports have described the efficacy and safety of second-line treatment of HER2-positive mGC patients with T-mab who were naïve to the drug. Methods: JFMC45-1102 was a multicenter, Phase II study. Patients positive for HER2 (IHC3+ or IHC2+/FISH+) with gastric adenocarcinoma confirmed histologically; older than ≥ 20 y; who received one or more prior chemotherapies but no prior therapy with T-mab; and normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Patients received paclitaxel (80 mg/m2on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg initial dose, followed by 6 mg/kg q3w). Treatment continued until their disease progressed; there was unacceptable toxicity or patient’s refused further treatment. The primary endpoint was overall response rate (ORR) evaluated according to RECIST ver. 1.0. Threshold and expected ORR were estimated at 15% and 30%, and secondary endpoints included progression free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. Results: Fourty-six patients were enrolled between September 2011 and March 2012. Patients characteristics were: gender (M/F) 37/9; median age 69; ECOG PS0/1/2, 35/10/1; unresectable/recurrence 25/21; number of prior treatments (1/2), 41/5. The ORR was 37.2% (95% CI: 23.0-53.3%). The median PFS and TTF were 5.2 months (95% CI 3.9-6.6) and 5.2 months (95% CI 3.9-6.6), respectively. The protocol was discontinued for 27 patients (87.1%) for disease progression, and one patient each (3.2%) for severe adverse events, physician’s recommendation, patient refusal, and treatment related death. Conclusions: Combination chemotherapy of paclitaxel plus T-mab showed promising activity and was tolerated well by patients naïve to T-mab who were positive for HER2 and treated previously for mGC. Clinical trial information: UMIN000006223.

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