Efficacy and Safety of Trastuzumab Biosimilar (CT-P6) Compared With Reference Trastuzumab in Patients With HER2-positive Advanced Gastric Cancer

4059 Background: A combination of S-1 and cisplatin (SP) has been the standard regimen for advanced gastric cancer (AGC) in East Asia. The combination of S-1 and oxaliplatin (SOX100) was demonstrated to be non-inferior to SP in the randomized phase III study. The ToGA study demonstrated that trastuzumab (T-mab) combination therapies with cisplatin and fluoropyrimidines improved the overall survival of patients with HER2-positive AGC. This multicenter study is the first phase II trial to assess the efficacy and safety of T-mab in combination with S-1 and oxaliplatin (HER-SOX130) in HER2-positive AGC. Methods: Patients with HER2-positive AGC or recurrent gastric cancer defined to be IHC 3+ or IHC 2+/FISH positive received 80 mg/m2 S-1 per day orally on days 1–14, 130 mg/m2 oxaliplatin intravenously on day 1, and T-mab (8-mg/kg loading dose and 6 mg/kg thereafter) intravenously on day 1 of a 21-day cycle until one of the criteria for withdrawal of the study treatment occurred. The primary end-point was the response rate (RR). Adverse events were recorded based on the NCI-CTCAE Vers.4.0. The threshold response rate was defined as 50%, and the expected rate was set at 70%, with an 80% power and a 1-sided alpha value of 0.05. The calculated sample size was 37 patients. Results: For this study, 42 patients (median age, 66 years) were enrolled from June 2015 to May 2016. Three patients were excluded owing to ineligibility. Efficacy and safety analyses were conducted in the full analysis set of 39 patients. The proportion of patients with IHC 3+ was 87%. The confirmed RR assessed by the independent review committee was 82.1(32/39) % (95% confidence interval [CI]: 67.3–91.0), and the disease control rate was 87.2(34/39) % (95% CI: 73.3–94.4). The incidence rates of grade 3 or 4 adverse events were as follows: neutropenia, 12.8%; thrombocytopenia, 17.9%; anemia, 10.3%; sensory neuropathy, 5.1%; anorexia, 17.9%; diarrhea, 7.7%; and teary eyes, 2.6%. Conclusions: HER-SOX130 demonstrated encouraging efficacy with a favorable safety profile. The survival benefit of this regimen needs to be validated by conducting further follow-up of patients. Clinical trial information: 000017552.

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A retrospective multicenter study evaluating the efficacy and safety of irinotecan in patients with advanced gastric cancer: Analysis of albumin-bilirubin (ALBI) grade.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.415 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 415-415

Author(s):

Iori Motoo ◽

Yoshito Komatsu ◽

Satoshi Yuki ◽

Shintaro Nakano ◽

Hiroshi Nakatsumi ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Multicenter Study ◽

Performance Status ◽

Efficacy And Safety ◽

Her2 Positive ◽

Prior Therapy ◽

Number Of Patients ◽

Grade 3 ◽

Retrospective Multicenter Study

415 Background: It is important to predict prognosis and risk of adverse events in patients with advanced gastric cancer receiving chemotherapy. Albumin-bilirubin (ALBI) grade is recently used as liver function assessment and prognosticator in hepatocellular carcinoma. Irinotecan is metabolized in the liver, so ALBI score may be useful for predicting irinotecan efficacy and safety. Methods: We conducted a retrospective multicenter study and investigated association between efficacy and ALBI grade in patients who received irinotecan monotherapy between January 2010 and December 2017. All patients had to receive fluoropyrimidine and platinum as prior therapy. The ALBI score is calculated by the equation: ALBI score = (log10 bilirubin [µmol/L] × 0.66) + (albumin [g/L] × −0.0852). As a result, ALBI grades 1, 2, and 3 were developed as follows: ALBI score ≤ −2.60 (ALBI grade 1), > −2.60 to ≤ −1.39 (ALBI grade 2), and > −1.39 (ALBI grade 3). Results: The number of patients with ALBI grade 1/2/3 is 100/68/5. In ALBI 1/2-3 patients, performance status 0/1/≥2 was 37/57/6 and 17/43/14, treatment line 2nd/3rd or later was 58/42 and 21/53, HER2 positive/negative 14/86 and 16/58, respectively. In ALBI 1/2-3 patients, median PFS was 3.3 and 2.3 months (HR = 0.684, P = 0.018) and median OS was 11.7 and 6.7 months (HR = 0.492, P < 0.001), respectively. In ALBI 1/2-3 patients, median treatment cycle which was 6 and 4 ( P = 0.09) and RDI were significantly different was, and RDI was 0.80 vs 0.70( P = 0.027), respectively.Hematological AEs were observed in 88% and 87% ( P = 1.000), severe hematological AEs (≥G3) were 41% and 58%( P = 0.040). Non-hematological AEs were 87% and 86%( P = 1.000), severe non-hematological AEs (≥G3) were 11% and 18% ( P = 0.257), respectively. Severe AEs in more than 5% patients were leukopenia (12% and 18%), neutropenia (23% and 28%), anemia (16% and 31%), and anorexia (2% and 10%).In multivariate analysis, ALBI grade was associated with shorter OS (ALBI 1 and 2-3: HR 1.773 95%C.I. 1.184-2.654, p = 0.005). Conclusions: ALBI grade might be both prognostic factor and risk factor in treatment with irinotecan monotherapy for patients with AGC.

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