A Case of Advanced Gastric Cancer with Peritoneal Metastasis Treated Successfully with Nivolumab

Peritoneal metastasis (PM) is detected in 14% of gastric cancers at the time of initial diagnosis, with a median survival time of 4 months. A 66-year-old woman diagnosed with cT4a(SE) N2M1(LYN) cStage IV was treated with three lines of chemotherapy for a year. During the third line of chemotherapy, computed tomography (CT) scan revealed a large amount of ascites, periportal collar sign, and bilateral ureteral stenosis owing to PM. The tumor biomarkers (CEA and CA 19–9) remained elevated similar to the initial levels. The patient was administered 3 mg/kg nivolumab intravenously biweekly as the fourth line of chemotherapy. Three months after the nivolumab treatment, gastroscopy revealed an extreme reduction of the tumor size, while CT scan revealed the absence of ascites and a well-controlled tumor. There was no immune-related adverse event with nivolumab during and after the treatment, and performance status improved to 0. The patient has been alive for about 2.5 years since her first visit with her sixth line of chemotherapy (docetaxel). We report a case of advanced gastric cancer with PM that was treated successfully with nivolumab.

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Treatment outcome and safety of docetaxel as the third-line chemotherapy in advanced gastric cancer after progression or after failure of FOLFOX and FOLFIRI-based sequential chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.133 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 133-133

Author(s):

I. Hwang ◽

J. Kang ◽

B. Park ◽

S. Park ◽

M. Jang ◽

...

Keyword(s):

Gastric Cancer ◽

Disease Progression ◽

Advanced Gastric Cancer ◽

Performance Status ◽

Progression Free Survival ◽

Salvage Chemotherapy ◽

The Third ◽

Third Line ◽

Grade 3 ◽

Line Chemotherapy

133 Background: We performed multicenter retrospective study to evaluate the activity and the safety of a docetaxel as the third-line chemotherapy in advanced gastric cancer (AGC) patients who had undergone oxaliplatin (FOLFOX) and irinotecan (FOLFIRI)-based chemotherapy regimens. Methods: Thirty-eight patients with AGC previously treated were eligible for this study. Patients received docetaxel 30 mg/m2 +/- cisplatin 30 mg/m2 IV on day 1, 8 or docetaxel 60 mg/m2 +/- cisplatin 60 mg/m2 IV on day 1 every 3 weeks until disease progression, and responses were assessed after every two cycles according to RECIST criteria and toxicity was evaluated by NCI-CTC. Results: Thirty-two out of 38 patients were evaluable for response. A total of 95.1 cycles of chemotherapy (median 2, range 0.5–7) were administered. Relative dose intensities of docetaxel and cisplatin were 93.4% and 87.8%, respectively. The overall response rate was 15.6% and the disease control rate was 50%. With a median follow-up duration of 3.1 months (range 0.3-14.3 months), 36 patients had disease progression, and 34 patients had died at the time of analysis. The median progression-free survival was 1.8 months (95% CI, 1.3–2.3 months). The median overall survival was 3.1 months (95% CI, 2.3–3.9 months). Grade 3 or 4 hematologic toxicities included neutropenia in thirteen patients (38.3%), febrile neutropenia in four patients (11.7%). and thrombocytopenia in one patient (2.9%). Other grade 3 or 4 toxicities included neuropathy in three patients (8.8%) and mucositis in two patients (5.9%). There were three treatment-related deaths (8.8%) caused by infection associated with neutropenia. Conclusions: Salvage docetaxel chemotherapy in AGC patients failed in oxaliplatin and irinotecan-based treatment is not recommend routinely. However, selected patients with good performance status and sufficient albumin levels may have derived some survival benefits from salvage chemotherapy. No significant financial relationships to disclose.

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A retrospective analysis of third-line treatment in advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.83 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 83-83

Author(s):

Yasunobu Ishizuka ◽

Tetsuji Terazawa ◽

Hiroki Yukami ◽

Toshifumi Yamaguchi ◽

Shin Kuwakado ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Response Rate ◽

Performance Status ◽

Predictive Biomarker ◽

Line Treatment ◽

The Third ◽

Third Line ◽

Grade 3 ◽

Third Line Treatment

83 Background: As a result of ATTRACTION2, nivolumab was added to the third line treatment in advanced gastric cancer (AGC), but the response rate was about 10%. As there is no predictive biomarker and no comparison with cytotoxic regimen, it is difficult to choice the regimen. Therefore, we examined the treatment outcome of cytotoxic regimen in third line treatment in the real world retrospectively. Methods: We retrospectively evaluated efficacy and safety of cytotoxic regimen as third-line treatment in patients with AGC between July 2015 and December 2017. Results: Among 138 patients received chemotherapy as first line, 29 patients (21%) received third line therapy. The characteristics were as follows; the median age, 70 years old (range 34-80); male/female, 19 (66%)/10 (34%); performance status (PS) 0/1/2, 7/18/4. The overall response rate was 19% and the disease control rate was 38%. The median overall survival (OS) was 6.6 months and the progression free survival was 3.8 months. The most common grade 3/4 hematological toxicities were neutropenia (27%), followed by anemia (27%) and febrile neutropenia (13.7%). Grade 3/4 nonhematological toxicities included anorexia (27.6%), diarrhea (10%), nausea (10%). Conclusions: Cytotoxic regimen as third line showed acceptable activity, but only 21% of patients could received the third line chemotherapy. The further investigation of predictive biomarker of nivolumab is expected.

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

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920942377 ◽

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.

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Optimal criteria of treatment change for advanced gastric cancer patients with nonmeasurable peritoneal metastasis alone.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.103 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 103-103

Author(s):

Hiroko Hasegawa ◽

Kazumasa Fujitani ◽

Shoichi Nakazuru ◽

Motohiro Hirao ◽

Eiji Mita ◽

...

Keyword(s):

Gastric Cancer ◽

Ct Scan ◽

Disease Progression ◽

Advanced Gastric Cancer ◽

Peritoneal Metastasis ◽

Chemotherapy Regimen ◽

Clinical Symptoms ◽

Performance Status ◽

Treatment Change ◽

Gastric Cancer Patients

103 Background: Palliative chemotherapy is the mainstay for the treatment of advanced gastric cancer (AGC) patients with peritoneal metastasis. In general, chemotherapy regimen is changed when patients show disease progression on CT scan. However, nearly 40% of these patients have no measurable lesions. It remains uncertain how clinicians can decide the timing of treatment change for AGC patients with non-measurable peritoneal metastasis alone. Methods: There were 217 patients with primary unresectable or recurrent gastric cancer at our institution between April, 2005 and March, 2012. Among them, 50 patients, who had histologically proven non-measurable peritoneal metastasis alone, were retrospectively identified and investigated in this study. They underwent measurements of tumor markers (TM) every month and abdominal CT scan every 2 months. For these 50 patients, chemotherapy regimen was changed based on the following different 2 criteria; 1. elevated TM and/or aggravated clinical symptoms alone (n=21), 2. radiologically confirmed disease progression (n=29). We assessed whether these two different criteria have any impact on overall survival (OS) by univariate and multivariate analyses. Results: Median survival time of all 50 patients was 604 days. Multivariate analysis identified pre-treatment performance status of 0-1 (hazard ratio (HR) 0.211, 95% confidence interval (CI) 0.045–0.998, P=0.049), initial hemoglobin level of 10 mg/dl or more (HR 0.114, 95% CI 0.014–0.936, P=0.043) and the TM / symptom based treatment change (HR 0.124, 95% CI 0.043–0.360, P=0.001) as significant prognostic factors for favorable OS. Conclusions: Early decision making of treatment change based on elevated TM and/or aggravated clinical symptoms alone might contribute to longer OS in AGC patients with non-measurable peritoneal metastasis alone.

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Analysis of a prospectively randomized comparison of doxorubicin versus 5-fluorouracil, doxorubicin, and BCNU in advanced gastric cancer: implications for future studies.

Journal of Clinical Oncology ◽

10.1200/jco.1986.4.9.1348 ◽

1986 ◽

Vol 4 (9) ◽

pp. 1348-1355 ◽

Cited By ~ 53

Author(s):

J A Levi ◽

R M Fox ◽

M H Tattersall ◽

R L Woods ◽

D Thomson ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Performance Status ◽

Single Agent ◽

Locally Advanced ◽

Poor Performance ◽

Poor Performance Status ◽

Measurable Disease ◽

Duration Of Response ◽

And Performance

A multi-institutional cooperative study of patients with locally advanced, recurrent, or metastatic gastric adenocarcinoma who had not previously received chemotherapy was conducted, prospectively randomizing patients to receive either doxorubicin or the three-drug combination, 5-fluorouracil (5-FU), doxorubicin (Adriamycin; Adria Laboratories, Columbus, Ohio), and BCNU (FAB). The 187 evaluable patients were initially stratified according to the presence of measurable or evaluable disease and performance status. There was a significantly higher response rate observed for FAB (40%) compared with doxorubicin (13%) among the 145 measurable-disease patients. Duration of response and survival were significantly longer for FAB in the measurable-disease group, but for the total patient population an early advantage for FAB in time to disease progression and survival was lost with continued follow-up. Median survival was 33 weeks for patients receiving FAB and 19 weeks for those receiving doxorubicin. Significant pretreatment factors adversely affecting survival included poor performance status, weight loss of greater than 10%, and more than two sites of metastases. Toxicity was not severe in either treatment arm, and only thrombocytopenia occurred significantly more often with FAB. It is contended that in the treatment of advanced gastric cancer, chemotherapy only exerts a relatively short-term and modest beneficial effect, most apparent in patients with intermediate tumor bulk. 5-FU remains the most active single agent, and combination chemotherapy has not yet proven its overall worth. Further studies are indicated comparing the most active combinations with 5-FU using optimal doses and schedules, and consideration must be given to the incorporation of no-treatment controls.

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Clinical effectiveness of apatinib at different doses in patients with advanced gastric cancer as the third-line or further treatment: Results from a post-marketing phase IV study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16037 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16037-e16037

Author(s):

Jin Li ◽

Shukui Qin ◽

Lu Wen ◽

Junsheng Wang ◽

Wenying Deng ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Initial Dose ◽

Performance Status ◽

Duration Of Treatment ◽

Ecog Performance Status ◽

Post Marketing ◽

Third Line ◽

Different Doses ◽

Phase Iv

e16037 Background: Apatinib, a highly selective VEGFR2 inhibitor, has shown a clinical benefit as third-line or further-line treatment in patients with gastric cancer in a randomized phase III study with the initial dose of 850mg. However, the study was conducted in a small scale (n = 267) under standardized conditions. Here, we assessed exposure and effectiveness of apatinib at different doses using data collected from a post-marketing phase IV study that included a broader patient population with a larger sample size. Methods: Patients with advanced or metastatic advanced gastric cancer or gastroesophageal junction adenocarcinoma who were aged 18-75 with ECOG performance status of 0-2 and failed at least two lines of chemotherapy were enrolled. Apatinib was recommended with an initial dose of 850 mg q.d orally, while the initial dose was determined at the discretion of the investigators. Administration of apatinib regarding the initial dose, duration of treatment, dose modification, average daily exposure dose (ADED) and its effect on progression-free survival (PFS) and overall survival (OS) were analyzed. Results: A total of 2004 patients were included in the intention-to-treat population. The median age was 59 (range, 19-85) years, 71.8% of patients were male, 84.2% had ECOG performance status of 0-1; 96.4% had stage IV disease, and 98.8% had metastases, among which 34.2% with more than 2 metastases. Five patients did not receive therapy. Compared to 5.5% of patients with the initial dose > 500mg, 94.1% was given at the initial dose≤500mg; 8.6% had ADED > 500mg and 91.1% had ADED ≤500mg. The median duration of treatment was 56 days. Treatment interruption and discontinuation, and dose reduction occurred in 34.4%, 24.5%, and 13.7% of patients due to adverse events, respectively. Survival analyses in the initial dose ≤500mg/ > 500mg subgroups showed median PFS of 2.6 months (95%CI 2.20-2.79) vs 2.7 months (95% CI 1.91-3.32), median OS of 5.6 months (95% CI 5.26-5.95) vs 5.9 months (95% CI 4.40-6.87). In the ADED ≤500mg/ > 500mg subgroups, the median PFS was 2.6 months (95% CI 2.14-2.76) vs 3.0 months (95% CI 2.27-3.61), and median OS was 5.7 months (95% CI 5.32-6.08) vs 6.1 months (95% CI 5.36-7.72). Conclusions: In conclusion, more than 90% of the patients received a lower dose regimen, which indicate dosage of 500mg or lower is a tolerated exposure. Furthermore, dose at 500mg or lower produced similar efficacy to that more than 500mg. Clinical trial information: NCT02426034.

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Association between UGT1A1 gene polymorphism and safety and efficacy of irinotecan monotherapy as the third-line treatment for advanced gastric cancer

Gastric Cancer ◽

10.1007/s10120-018-00917-5 ◽

2019 ◽

Vol 22 (4) ◽

pp. 778-784 ◽

Cited By ~ 3

Author(s):

Toshifumi Yamaguchi ◽

Satoru Iwasa ◽

Hirokazu Shoji ◽

Yoshitaka Honma ◽

Atsuo Takashima ◽

...

Keyword(s):

Gastric Cancer ◽

Gene Polymorphism ◽

Advanced Gastric Cancer ◽

Line Treatment ◽

Safety And Efficacy ◽

Ugt1a1 Gene ◽

The Third ◽

Third Line ◽

Third Line Treatment

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

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.154 ◽

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.

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