Efficacy and safety of nivolumab and irinotecan as third-line chemotherapy for advanced gastric cancer: A multi-institutional retrospective study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 396-396
Author(s):  
Ryosuke Kumanishi ◽  
Seiichiro Mitani ◽  
Shigenori Kadowaki ◽  
TOMOHIRO MATSUSHIMA ◽  
Naoki Takahashi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Group Performance ◽  
Interaction Analysis ◽  
Eastern Cooperative Oncology Group ◽  
Lower Grade ◽  
Efficacy And Safety ◽  
Clinical Factors ◽  
Ecog Ps

396 Background: Although nivolumab (NIVO) and irinotecan (IRI) are currently used as third- or later-line therapy for advanced gastric cancer (AGC), few direct comparisons between them have been available. The present study therefore aims to compare the efficacy and safety of NIVO with IRI and explore clinical factors that predict efficacy. Methods: Patients with AGC who underwent NIVO or IRI treatment between November 2016 and June 2018 at three institution were retrospectively examined, subsequently evaluating response rates (RR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). The main inclusion criteria were patients pretreated with fluoropyrimidines and taxanes, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0–2, and no previous NIVO or IRI treatment. Results: A total of 71 and 61 patients received NIVO and IRI, respectively, with both groups having similar baseline characteristics, except for gender. Efficacies were as follows (NIVO/IRI): RR, 20%/6% (p = 0.17); median PFS, 1.6 months (m)/1.8 m (HR 0.93, p = 0.67); median OS, 6.4 m/6.4 m (HR 0.91, p = 0.61); 1-year survival rate, 24.9%/19.3% (p = 0.61), respectively. Interaction analysis found no significant interaction between drugs and various factors such as ECOG PS (p = 0.59) and neutrophile/lymphocyte ratio (p = 0.33) related to OS. Subsequent chemotherapy agents were administered to 32 patients (45%) in the NIVO group (17 patients out of them received IRI) and 36 patients (59%) in the IRI group (23 patients out of them received NIVO) (p = 0.12). NIVO tended to have lower grade 3 or more AEs than IRI, especially neutropenia (3% vs. 28%, respectively; p < 0.01) and febrile neutropenia (1% vs. 8%, respectively; p = 0.09), as well as neutropenia, nausea, diarrhea, constipation, fatigue, and anorexia of any grade. Five patients developed immune-related adverse events in the NIVO group: pneumonitis (n = 1) and rash (n = 4). Conclusions: Although no remarkable differences in efficacy were found between NIVO and IRI for AGC, NIVO had a better safety profile compared to IRI. This study found no clinical factors that predicted efficacy.

Prognostic factors for survival in patients with advanced gastric cancer treated with chemotherapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 142-142
Author(s):  
Montserrat Mangas ◽  
Alberto Carmona Bayonas ◽  
Maria Luisa Sanchez Lorenzo ◽  
Avinash Ramchandani ◽  
Teresa Garcia ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Advanced Gastric Cancer ◽  
Group Performance ◽  
Gastroesophageal Junction ◽  
Cox Proportional Hazards Model ◽  
Her2 Status ◽  
Her2 Positive ◽  
Ecog Ps

142 Background: A prognostic model in advanced gastric cancer that integrates the Her2 status,histopathological classifications and other patient’s or treatment-dependent parameters is lacking. The aim is to identify clinicopathological factors for overall survival in a cohort of patients with advanced gastric cancer. Methods: 526 consecutive patients with advanced adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach were analyzed. All patients were treated with poly-chemotherapy ( ≥ 2 drugs) at 19 Spanish and one Chilean centers between 2012 and 2015. Characteristics of patients, tumors, therapies and pathological factors, were analyzed by a Cox proportional hazards model. Results: The median overall survival was 10.3 months [95% confidence interval (CI), 9.5-11.1], and the time to progression was 6.7 months (95% CI, 6.1-7.2). Independent prognostic factors associated with overall survival were: distal non-diffuse histopathological subtype (hazard ratio, (HR) 0.73), Her2 positive 3+ (HR 0.54), Her2 positive 2+ with FISH + (HR 0.68), surgery of metastases (HR 0.34), Eastern Cooperative Group performance status (ECOG PS) 2 (HR 2.5), ECOG PS 3 (HR 7.37), and only distant lymph node metastases (HR 0.63) (Table 1). Conclusions: We have identified clinicopathological prognostic factors that could be important to stratify advanced gastric cancer, with potential implications in research and treatment. [Table: see text]

Prognostic impact of immune-related adverse events with nivolumab in patients with advanced gastric cancer: A multicenter retrospective analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 347-347
Author(s):  
Yuno Ohya ◽  
Takayuki Ando ◽  
Akira Ueda ◽  
Kohei Ogawa ◽  
Iori Motoo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Practice ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Retrospective Analysis ◽  
Prognostic Impact ◽  
Significant Difference ◽  
Metastatic Sites ◽  
Practice Methods ◽  
Ecog Ps

347 Background: Nivolumab was established as one of the standard treatments for previously treated advanced gastric cancer (AGC). The aim of this study is to evaluate the frequency of immune-related adverse events (irAEs) with Nivolumab and its impact on treatment efficacy in clinical practice. Methods: We performed multicenter retrospective analysis, which included 90 patients with advanced gastric cancer who received Nivolumab treatment between October 2017 and September 2019. The frequency of irAEs and its treatment outcome were evaluated, and survival was compared during Nivolumab treatment. Results: The characteristics of 90 patients in this analysis were as follows: median age (range), 68 (36-85); male/female, 56/34; ECOG PS 0-1/≥2, 62/28; number of metastatic sites 1/≥2, 36/56; treatment line 3/≥4, 63/27. Median treatment cycle of nivolumab treatment was 3 (range 1-26). The overall response in 68 patients with target lesions was 6.3% (4/68), and the median PFS and OS was 1.5 and 4.3 months, respectively. IrAEs were observed in 8 patients (8.8%), including grade 4 pneumonitis, grade 2 or 3 adrenal insufficiency, and grade 2 hypothyroidism, encephalitis, and immune thrombocytopenia. Median time to onset of irAEs was 1.3 (range 0.6-10.5) months. Six were treated with systemic corticosteroid therapy, and all irAEs were relieved. The median PFS and OS were 4.7 months (95%CI, 1.2-9.3) and 12.2 months (95% CI, 3.2-not reached) in patient with irAEs, and 1.4 months (95%CI, 1.1-1.9) and 4.1 months (95%CI, 2.6-6.6) in those without, respectively. There was significant difference in the PFS (p=0.005) and OS (p=0.03). Conclusions: Nivolumab was effective and well tolerated even in clinical practice. Development of irAEs may be associated with better outcome of Nivolumab in patients with AGC.

Phase II Trial of Biweekly Infusional Fluorouracil, Folinic Acid, and Oxaliplatin in Patients With Advanced Gastric Cancer

2004 ◽  
Vol 22 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Salah-Eddin Al-Batran ◽  
Akin Atmaca ◽  
Susanna Hegewisch-Becker ◽  
Dirk Jaeger ◽  
Sabine Hahnfeld ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Folinic Acid ◽  
Advanced Gastric Cancer ◽  
Intravenous Infusion ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Who Grade ◽  
Grade 3

Purpose To evaluate the toxicity and activity of infusional fluorouracil (FU), folinic acid (FA), and oxaliplatin, administered every 2 weeks in patients with metastatic gastric cancer. Patients and Methods Forty-one previously untreated patients with measurable adenocarcinoma of the stomach were eligible for the study. Patients received FU 2.6 g/m2 (24-hour continuous infusion), FA 500 mg/m2 (2-hour intravenous infusion), and oxaliplatin 85 mg/m2 (2-hour intravenous infusion) every 2 weeks for 6 weeks. Treatment was continued until progression of disease was observed. Results All patients were assessable for toxicity and 37 of 41 patients were assessable for response. Patient characteristics were: sex (male, 28; female,13), median age 60 years (range, 20 to 77 years), and median Eastern Cooperative Oncology Group performance status of 1. Response was evaluated every 6 weeks. Of 37 assessable patients, one complete and 15 partial remissions were observed (overall response rate, 43%). Stable disease was observed in 12 patients (32%) and progressive disease in nine patients (24%). The median overall survival was 9.6 months. WHO grade 3 or 4 hematologic toxicities included neutropenia in two patients (4.9%) and thrombocytopenia in one patient (2.4%). Other WHO grade 3 or 4 toxicities included diarrhea in three patients (7.3%) and vomiting in two patients (4.9%). There were no cases of grade 3 peripheral neuropathy and no treatment-related deaths. Conclusion Biweekly fluorouracil, folinic acid, and oxaliplatin is active and well-tolerated in patients with advanced gastric cancer. Response rates, time to progression, and overall survival were comparable to those achieved with other combination chemotherapy regimens, including FOLFOX6, with significantly less toxicity.

Efficacy and safety of taxane-monotherapy in advanced gastric cancer refractory to triplet chemotherapy with docetaxel, cisplatin, and S-1: A multicenter retrospective study.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 154-154
Author(s):  
Sadayuki Kawai ◽  
Sakura Iizumi ◽  
Atsuo Takashima ◽  
Yukiya Narita ◽  
Masahiro Tajika ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
The Third ◽  
Third Line ◽  
Ecog Ps ◽  
Third Line Treatment

154 Background: While taxane-monotherapy following fluoropyrimidine plus platinum is recognized as the standard treatment strategy for advanced gastric cancer, triplet chemotherapy with docetaxel, cisplatin and S-1 (DCS) is another option for first-line therapy in Japan. However, efficacy of taxane after DCS therapy has not been sufficiently evaluated. Methods: We retrospectively evaluated the efficacy and safety of taxane-monotherapy after DCS between January 2010 and April 2015 for advanced gastric cancer. The taxane-monotherapy included weekly paclitaxel (PTX) (80 mg/m2, day 1, 8 and 15 of a 28-day cycle) and triweekly nab-PTX (260 mg/m2, day 1). Other selection criteria were: ECOG PS < 2; adequate organ function; no severe ascites; HER2-negative. Results: Thirty of 92 patients who had been treated with DCS received taxane-monotherapy. Fifteen and 15 patients received taxane-monotherapy as the second and third-line treatment, respectively. Patients characteristics of each group (2nd/3rd) were; median age: 64/62 (range 27-75/42-75); ECOG PS ≤ 1: 14/13; number of metastatic sites ≥ 2: 9/12; median taxane-free interval from first-line treatment: 1.6/3.4 (range 0.9-2.3/2.2-8.3) months; median total dose of prior DTX: 349/208 (range 39-844/141-685) mg/m2. Number of patients who received PTX/nab-PTX were 10/5 and 13/2 in the second and third line treatment. Median relative dose intensity of taxane was 96.4% (range 57.6-172.9%) in the second-line, 98.5% (44.0-166.8%) in the third-line group. Response rate and disease control rate were 0% and 37.5% in the second-line, and 0% and 38.5% in the third-line group. Median progression free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line. Grade 3 or 4 neutropenia, anemia, and anorexia, occurred in 33%, 13% and 13% in the second-line group, and 6.7%, 13% and 6.7% in the third–line group, associated with no treatment related death. Conclusions: It is suggested that taxane-monotherapy has acceptable toxicities but insufficient efficacy in advanced gastric cancer patients after DCS therapy.

Efficacy and safety of nab-paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment for patients with advanced gastric cancer: A single institutional experience.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 322-322
Author(s):  
Mashiro Okunaka ◽  
Daisuke Kotani ◽  
Ken Demachi ◽  
Akihito Kawazoe ◽  
Takayuki Yoshino ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Peritoneal Metastasis ◽  
Objective Response ◽  
Randomised Trial ◽  
Rank Test ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety

322 Background: Nanoparticle albumin-bound (nab)- paclitaxel (PTX) was non-inferiority to solvent-based paclitaxel as second-line for advanced gastric cancer (AGC) with fewer infusion-related reactions and a trend toward improved overall survival (OS) in patients (pts) with peritoneal metastasis (PM) or ascites in ABSOLUTE trial (Shitara K et al. Lancet Gastroenterol Hepatol. 2017). Furthermore, safety and efficacies of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial (Bando H, et al. EJC 2018), although no randomised trial with PTX plus RAM is reported so far. Methods: We retrospectively reviewed consecutive pts with AGC receiving nab-PTX plus RAM or PTX plus RAM as second-line chemotherapy from June 2015 to January 2019 at the National Cancer Center Hospital East. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Progression-free survival (PFS) was calculated using the Kaplan-Meier method, and the differences were evaluated using the log-rank test. Results: A total of 257 pts were included for analysis with 118 pts treated with nab-PTX plus RAM and 139 pts with PTX plus RAM. 151 pts (59%) had peritoneal metastasis and 76 pts (30%) were associated with moderate or massive amounts of ascites. Objective response rates were similar between two groups (nab-PTX plus RAM 34.1% vs. PTX plus RAM 28.0%, p = 0.36). There were no significant differences in PFS (median 3.9 vs. 3.9 months, log-rank p = 0.34; hazard ratio [HR] = 1.14). HR of PFS was 0.96 in pts with PM and 0.79 in pts with moderate or massive ascites. The major grade 3 or higher adverse events were neutropenia (nab-PTX plus RAM 55.1% vs. PTX plus RAM 55.4%), leucopenia (28.8 vs. 35.3%), thrombocytopenia (5.1 vs. 2.9%), and febrile neutropenia (5.1 vs 9.4%). Conclusions: Efficacy and safety of nab-PTX plus RAM were comparable to those of PTX plus RAM in pts with AGC in clinical practice. nab-PTX plus RAM is a treatment option as second-line treatment in pts with AGC.

scholarly journals Clinical features as potential prognostic factors in patients treated with nivolumab for highly pretreated metastatic gastric cancer: a multicenter retrospective study

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Akihiko Sano ◽  
Makoto Sohda ◽  
Nobuhiro Nakazawa ◽  
Yasunari Ubukata ◽  
Kengo Kuriyama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Retrospective Study ◽  
Adverse Events ◽  
Clinical Features ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
To Receive

Abstract Background Although nivolumab (anti-programmed cell death-1 antibody) is a promising approach for advanced gastric cancer (AGC), the response rate remains limited. The aim of this multicenter retrospective study was to determine if clinical features could serve as prognostic factors of the efficacy of nivolumab in patients with AGC. Methods Fifty-eight patients with AGC who were treated with nivolumab as a third or later line from October 2017 to December 2018 at any of five clinical sites were enrolled in the study. The correlation between the best overall response and clinical features was investigated. Overall survival and progression-free survival after initiation of nivolumab were calculated and clinical features that could be predictors of the prognosis were sought. Results The disease control rate (DCR) for nivolumab was 36.2% and was significantly correlated with performance status (p = 0.021), metastasis to one organ (p = 0.006), and grade 2 or higher immune-related adverse events (p = 0.027). There was also a significant association between response to nivolumab and ability to receive subsequent chemotherapy (p = 0.022). In the analysis of overall survival, the following variables were identified as being significantly associated with a poor outcome: Eastern Cooperative Oncology Group performance status ≥1, prior treatment with trastuzumab, no immune-related adverse events, lack of a response to nivolumab, and inability to receive subsequent chemotherapy. Conclusion The findings of this study suggest that nivolumab may be ineffective for AGC in patients with poor performance status and those with a history of treatment with trastuzumab.

scholarly journals Meta-Enrichment Analyses to Identify Advanced Gastric Cancer Patients Who Achieve a Higher Response to S-1/Cisplatin

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 871
Author(s):  
Takeuchi ◽  
Jaffer A ◽  
Fang ◽  
Pfeiffer ◽  
Takeuchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Enrichment Analysis ◽  
High Response ◽  
Phase Iii ◽  
P Value ◽  
Data Set ◽  
Specific Patient

The Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study (FLAGS) and the Diffuse Gastric and Esophagogastric Junction Cancer S-1 Trial (DIGEST) have shown that patients with advanced gastric cancer treated with S-1/Cisplatin (CS) have similar overall survival (OS) compared to 5-fluorouracil/cisplatin (CF). The purpose of this analysis was to identify patients who may specifically benefit from CS using meta-enrichment analysis of the combined two datasets. Eleven clinico-pathological factors were selected and a high response enrichable population was determined. The efficacy of CS in the combined data set of 1365 patients (n = 1019 from FLAGS and n = 346 from DIGEST) was analyzed. We identified 683 patients (n = 374 from CS, n = 309 from CF) as the high response enrichable population who were classified as those with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1, more than two metastatic sites and low neutrophil-lymphocyte ratio (log(NL ratio)). In the high response enrichable population, the median OS in the CS group was 241 days compared to 210 days in the CF group (hazard ratio 0.776; 95% confidence interval 0.658 to 0.915; p-value 0.004). Through meta-enrichment analysis, the high response enrichable population to CS was identified. Our findings show the clinical importance of selecting the appropriate treatment based on specific patient characteristics.

Systemic chemotherapy for gastric cancer with early recurrence after adjuvant S-1 monotherapy: A multicenter retrospective study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 154-154
Author(s):  
Hiroko Hasegawa ◽  
Seiichiro Mitani ◽  
Takeru Wakatsuki ◽  
Hiroki Hara ◽  
Motohiro Hirao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Therapy ◽  
Poor Prognosis ◽  
Systemic Chemotherapy ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Early Recurrence ◽  
Her2 Status ◽  
Survival Outcomes ◽  
Ecog Ps

154 Background: S-1 monotherapy is one of the standard adjuvant treatments for stage II or III gastric cancer patients (pts). Early recurrence after adjuvant therapy has a poor prognosis and the optimal regimen remains to be established. This study aimed to clarify the treatment outcomes of systemic chemotherapy and explore encouraging regimens for gastric cancer pts with early recurrence. Methods: We retrospectively reviewed gastric cancer pts at four institutions who underwent curative gastrectomy followed by adjuvant S-1 monotherapy and identified pts who developed recurrence during the adjuvant therapy or within 6 months after completion between 2005 and 2015. Other main eligibility criteria were Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2, adequate organ function and no massive ascites. The Cox proportional hazards model was used to evaluate the survival outcomes, adjusting for relevant factors. Results: A total of 112 pts were included. Pts characteristics were as follows: median age (range), 62 (29-83) years; male/female, 84/28; ECOG-PS 0/1/2, 39/63/10; diffuse/intestinal, 73/39; HER2 status positive/negative/unknown, 17/46/49; metastatic site liver/peritoneum, 32/44; and number of metastatic sites 1/≥2, 94/18. The taxane-based regimens were as follows: weekly paclitaxel (PTX) (38), nab-PTX (4), trastuzumab (Tmab) + PTX (4), S-1 + PTX (3), and the others (4). The platinum-based regimens were irinotecan + cisplatin (IP) (31), capecitabine + cisplatin (XP) (7), S-1 + cisplatin (5), Tmab + XP (4), and the others (2). For all pts, the median PFS and OS were 3.7 months (M) and 11.4 M, respectively. After excluding HER2-positive pts, there were no statistically significant differences between the taxane-based and platinum-based regimens in survival outcomes (median OS, 7.6 M vs. 12.2 M; adjusted HR = 0.93, 95% CI 0.58-1.49), nor between IP and the other platinum-based regimens (median OS, 11.8 M vs. 13.3 M; adjusted HR = 0.64, 95% CI 0.28-1.46). Multivariate analysis showed treatment regimen was not a prognostic factor. Conclusions: The regimens so far selected for gastric cancer with early recurrence resulted in similar, poor prognosis.

scholarly journals Clinical and molecular factors for selection of nivolumab or irinotecan as third-line treatment for advanced gastric cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592094237
Author(s):  
Takahiro Ishii ◽  
Akihito Kawazoe ◽  
Akinori Sasaki ◽  
Saori Mishima ◽  
Sawada Kentaro ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Line Treatment ◽  
Her2 Positive ◽  
The Third ◽  
Third Line ◽  
Third Line Treatment

Background: The use of nivolumab or irinotecan as the third-line treatment for patients with advanced gastric cancer (AGC) remains controversial. Methods: This study analyzed patients with AGC treated with nivolumab or irinotecan (nivolumab group or irinotecan group, respectively) from May 2016 to April 2019 following two or more previous lines of chemotherapy. Univariate survival analysis was conducted to identify the clinical and molecular factors associated with progression-free survival (PFS). Results: A total of 156 patients (74 treated with nivolumab and 82 treated with irinotecan) were analyzed. The median PFS was 1.9 months in both treatment groups. The median overall survival (OS) was 7.2 and 6.2 months in the nivolumab and irinotecan groups, respectively. Eastern Cooperative Oncology Group performance status of 1 or more, liver metastasis, a large tumor size at baseline, and HER2-positive status were associated with a worse PFS in the nivolumab group compared with the irinotecan group. The nivolumab group showed a significantly longer PFS (median 3.1 versus 2.0 months) and OS (median 12.9 versus 7.8 months) than the irinotecan group in patients with 0 or 1 of these factors, whereas the irinotecan group showed a significantly longer PFS (median 1.0 versus 1.8 months) and a trend of longer OS (median 3.9 versus 6.1 months) in patients with ⩾2 of these factors. Conclusions: Some clinical and molecular factors were associated with outcomes following nivolumab or irinotecan as the third- or later-line treatment in patients with AGC. These factors must be considered while selecting an optimal treatment option.

A phase II study (KSCC/HGCSG/CCOG/PerSeUS1501B) of trastuzumab plus S-1 and oxaliplatin for HER2-positive advanced gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4059-4059 ◽  
Author(s):  
Katsunori Shinozaki ◽  
Satoshi Yuki ◽  
Tomomi Kashiwada ◽  
Tetsuya Kusumoto ◽  
Masaaki Iwatsuki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Incidence Rates ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Standard Regimen

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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