Clinical efficacy and safety in gastric cancer patients treated with apatinib: A retrospective real-world study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15522-e15522
Author(s):  
Ning Li ◽  
Yali Du ◽  
Wenying Deng ◽  
Yijie Ma ◽  
Xinyi Yang ◽  
...  

e15522 Background: This study aimed to explore the efficacy, safety of apatinib and analyze the effects of HER2 mutation status and treatment lines on gastric cancer (GC) patients (pts) treated with apatinib in real-world clinical practice. Methods: We retrospectively analyzed the study data from Linkdoc database with 270 pts who were pathologically or cytologically diagnosed GC and treated with apatinib during January 2015 to November 2018 in Henan Cancer Hospital. Survival was estimated by Kaplan-Meier method. Results: In this study, there were 180 (66.7%) male, with median age of 59 years. The vast majority of pts (259/95.9%) had adenocarcinoma and 86.3% of pts were in stage IV. HER2 was positive in 33.0% of 100 treated pts undergoing HER2 mutation testing. Apatinib was mainly used as second-line treatment (122/45.2%), followed by third-line (82/30.4%), first-line (56/20.7%), fourth- and further-line (22/8.1%), adjuvant (12/4.4%) and neoadjuvant treatment (1/0.4%). Pts received apatinib alone or combined with chemotherapy were 175 (64.8%) and 119 (44.1%), with 53.6% administered at an initial dose of 500 mg. Of all the 270 enrolled pts, the median progression free survival (mPFS) and median overall survival (mOS) were 4.3 months (95% CI: 3.5-5.0) and 6.1 months (95% CI: 5.1-8.4), respectively. For treatment lines subgroup, the mOS was 12.6 months (95% CI: 3.5-NE) in adjuvant treatment; 8.9 months (95% CI: 4.3-12.6) in first-line; 7.3 months (95% CI: 5.0-9.7) in second-line; 6.2 months (95% CI: 5.1-9.9) in third-line; 4.0 months (95% CI: 1.6-6.9) in fourth- and further-line treatment. For HER2-negative pts, the mOS was slightly longer than those of HER2-positive pts (5.7 months vs. 4.5 months), however, the difference was not statistically significant ( p = 0.5185). The most common adverse events were fatigue (25.9%), anemia (24.8%), hypertension (9.3%) and vomiting (9.3%). Conclusions: This real world study revealed that the clinical efficacy of apatinib in GC pts was satisfying and the toxicity was tolerable and controllable. Pts received apatinib in ≤ second-line treatment may gain better survival benefits, and little difference was found in survival outcomes between pts with or without HER2 mutations.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 94-94 ◽  
Author(s):  
Juliette Palle ◽  
David Tougeron ◽  
Astrid Pozet ◽  
Emilie Soularue ◽  
Pascal Artru ◽  
...  

94 Background: Trastuzumab in combination with platinum-based chemotherapy is the standard first line regimen in HER2 positive advanced gastric cancer. However, there is no data concerning continuation of trastuzumab beyond first line progression. Methods: This retrospective multicenter study include all consecutive patients with HER2 + advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received after progression of trastuzumab plus platinum-based chemotherapy, a second line chemotherapy with irinotecan, taxane or platinum salt, with or without trastuzumab. The prognostic variables with P values ≤0.10 in univariate analysis were eligible for the Cox multivariable regression model. Results: From August 2007 to March 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; PS 0-1, 71.2%) with advanced (metastatic : 99%) gastric (45.2%) or GEJ (54.8%) cancer. All patients had received first line treatment based on trastuzumab plus fluoropyrimidine and cisplatin (n=54; 51.9%) or oxaliplatin (n=50; 48.1%). As second line chemotherapy, 67 patients (64.4%) received FOLFIRI regimen, including 19 who have continued trastuzumab; 23 patients (22.1%) received a taxane regimen (paclitaxel or docetaxel), including 12 with trastuzumab; and 14 patients (13.5%) received a platinum-based chemotherapy (different from that used in first-line), including 8 with trastuzumab. When considering all regimens of second-line chemotherapy, continuation (n=39) versus discontinuation (n=65) of trastuzumab was significantly associated with an increase on PFS (4.4 vs 2.3 months; p=0.002) and OS (12.6 vs 6.1 months; p=0.001). In multivariate Cox model (including ECOG PS, tumor grade, number of metastatic site, and second-line treatment), continuation of trastuzumab was significantly associated with longer PFS (HR=0.56; 95%CI [0.35-0.89]; p=0.01) and OS (HR=0.47; 95%CI [0.28-0.79]; p=0.004). Conclusions: This study suggests that maintenance of trastuzumab plus second line chemotherapy beyond disease progression has clinical benefit in patients with HER2 positive advanced gastric cancer. These results deserve a prospective randomized validation.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 154-154
Author(s):  
Sadayuki Kawai ◽  
Sakura Iizumi ◽  
Atsuo Takashima ◽  
Yukiya Narita ◽  
Masahiro Tajika ◽  
...  

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.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 113-113 ◽  
Author(s):  
Yang Chen ◽  
Guanghai Dai

113 Background: Although the clinical trial WJOG7112G was failed to prove weekly paclitaxel with trastuzumab in patients with HER2-positive gastric or gastro-esophageal junction (GEJ) cancer refractory to trastuzumab is better than paclitaxel alone, there are limited data concerning efficacy of continuing trastuzumab beyond first-line progression in the real world. Methods: This retrospective study included all consecutive patients with HER2-positive advanced gastric or GEJ adenocarcinoma who received a chemotherapy with trastuzumab in first-line, or second-line, or third-line therapy between 2010 and 2016 in Chinese People’s Liberation Army General Hospital. Progression-free survival (PFS) and overall survival (OS) were estimated from the initial chemotherapy. Results: A total of 67 patients (median age, 59 years; male, 71.6%) with HER-2 positive advanced gastric or GEJ adenocarcinoma treated with chemotherapy plus trastuzumab initially in first (n = 50), second (n = 13), or third (n = 4) line of therapy were included. The median OS of trastuzumab for initial first-line, second-line, or third-line treatment was 16.7 months, 14.2 months, and 13.2 months, respectively (P = 0.83). In patients initially using trastuzumab in first-line therapy, the continuation (n = 19) versus discontinuation (n = 31) of trastuzumab beyond first-line progression was significantly associated with an improvement of median PFS (3.4 versus 1.9 months; P = 0.02), but not OS (19.0 versus 16.4 months; P = 0.13). In the multivariate analysis including the ECOG PS, number of metastatic sites and chemotherapy regimen, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.77; 95% CI, 0.41-0.93; P = 0.04), but not OS (HR, 0.85; 95% CI, 0.56-1.22; P = 0.24). Conclusions: This study suggests that HER-2 positive advanced gastric or GEJ adenocarcinoma patients could benefit from trastuzumab no matter when they start receiving trastuzumab. The continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer for PFS, but not for OS. Large scale prospective randomized validation is warranted.


2019 ◽  
Vol 10 (4) ◽  
pp. 591-597 ◽  
Author(s):  
Valentina Fanotto ◽  
Lorenzo Fornaro ◽  
Roberto Bordonaro ◽  
Gerardo Rosati ◽  
Lorenza Rimassa ◽  
...  

2019 ◽  
Vol 11 ◽  
pp. 175883591986752 ◽  
Author(s):  
Elizabeth C. Smyth ◽  
Markus Moehler

Survival for patients with unresectable advanced or recurrent gastric cancer (GC) remains poor and the historical lack of evidence-based therapeutic options after second-line therapy is reflected in current clinical guidelines for this condition. Despite uncertainty about optimal therapeutic strategies, further treatment is appropriate for some patients after failure of second line and may prolong survival. This approach has been reported in clinical trials and is becoming more common in real-world clinical settings. Several prognostic factors may increase the likelihood that a patient will be eligible for treatment in the third-line setting, including geographic location, status at diagnosis and response to treatment. There has been little progress over the last decade until the results from two large phase III randomized controlled trials completed in the last year: the ATTRACTION-2 trial with the programmed cell death-1 (PD-1) inhibitor, nivolumab, in an Asian population; and the TAGS trial with the oral chemotherapy trifluridine/tipiracil in a global population. Both ATTRACTION-2 and TAGS reported positive results in third-line treatment in advanced GC in specific patient groups. A further recently reported study, KEYNOTE-059, which was a single-arm phase II trial of the PD-1 inhibitor pembrolizumab in a mainly non-Asian population, has provided evidence supporting the use of this immunotherapy in patients with advanced GC. As further third-line options become available, more GC patients are expected to benefit from an individualized evidence-based approach to later-line therapy, with a common goal of extending survival and improving outcomes for their refractory disease.


2014 ◽  
Vol 25 ◽  
pp. v53
Author(s):  
Yukiya Narita ◽  
Shigenori Kadowaki ◽  
Hiroya Taniguchi ◽  
Daisuke Takahari ◽  
Takashi Ura ◽  
...  

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