PD-L1 expression in patients with metastatic gastric cancer in South Korea.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1571-1571
Author(s):  
Hyo Song Kim ◽  
Ting Wu ◽  
Hyunki Kim ◽  
Hyun Cheol Chung ◽  
Jaffer A. Ajani ◽  
...  

1571 Background: Data are limited and conflicting regarding programmed death ligand 1 (PD-L1) expression as prognostic of clinical outcomes in patients (pts) with metastatic gastric cancer (mGC) treated with standard of care (SOC). Factors affecting the association between PD-L1 expression and outcomes include type of assay and antibody, scoring system for PD-L1 expression, and method of tissue collection. We analyzed the association between tumor PD-L1 expression and clinical parameters in Korean pts with inoperable mGC. Methods: A retrospective study was performed in 201 pts with inoperable mGC from Yonsei Cancer Center in Seoul, South Korea. Biopsy samples were collected at diagnosis. Tumor PD-L1 expression was measured by IHC using the 22C3 PD-L1 antibody pharmDx kit (Dako North America, Carpinteria, CA, USA). PD-L1 positivity was defined as a combined positive score (CPS) of ≥1%, where CPS is PD-L1+ cells (tumor cells, macrophages, lymphocytes) over the total number of tumor cells, expressed as a percentage. Survival was analyzed using Kaplan-Meier methods, log-rank test, and Cox proportional hazards models, adjusting for age, sex, and ECOG performance status. Results: A total of 189/201 (94%) pts received chemotherapy as SOC and were included in this analysis. Median age was 56 years (range, 21-82), 37% of pts were women, and 28% had a BMI ≥24. All pts had stage IV metastatic disease and 27%, 49%, and 24% had well to moderately differentiated, poorly differentiated, and signet ring cell tumors, respectively. Prevalence of PD-L1 positivity was 72.5%. PD-L1 positivity was not associated with age, BMI, or histologic grade. Median overall survival (OS) for the PD-L1+ and PD-L1– groups was 10.9 and 10.2 months, respectively ( P= 0.92). The hazard ratio for the PD-L1+ vs the PD-L1–group was 1.02 (95% CI, 0.74-1.39) before adjusting for age, sex, and ECOG performance status and 1.08 (95% CI, 0.77-1.51) after adjusting. Conclusions: Based on this preliminary assay and cutoff, results suggest that PD-L1 expression is not a prognostic factor for mGC. Additional biomarker analyses (eg, immune gene expression profile and microsatellite instability) are planned.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4571-4571
Author(s):  
J. Ocvirk ◽  
M. Rebersek ◽  
E. Skof

4571 Background: In phase II studies ECF with 5- FU inf. resulted in response rates (RR) > 50 %. Despite high responses the potential drawback of ECF may be the poor patient’s (pts) acceptability of the indwelling catheter and external infusion pump and related complications: sepsis, catheter-related infections, shoulder pain, thrombosis and pneumothorax. Capecitabin can maintain a constant level of 5- FU without complications and inconvenience associated with central venous access. The aim was to compare the efficacy and safety ECF versus ECX. Secondary endpoint was overall survival. Methods: Pts with histological proven, previously untreated advanced or metastatic gastric cancer, >18 years, ECOG performance status 0- 2 and adequate organ and hematological function were randomized to ECF or ECX. In ECF epidoxorubicin 50 mg/m2 and cisplatin 60 mg/m2 were administrated on day 1 by i.v., 5- FU 200 mg/m2/day was administrated by cont. inf. day 1- 14 of each cycle. Cycle was repeated every 3 weeks. In ECX epidoxorubicin 50 mg/m2 and cisplatin 60 mg/m2 were administrated on day 1 by i.v., capecitabin 825 mg/m2 twd was administrated orally day 1- 14. Cycle was repeated every 3 weeks. Results: Seventy- one pts were enrolled in this study between Jan 03 to Dec 05. Male 80 %, median age 56 yrs (40- 77). Thirty pts received ECF and 41 pts received ECX . All pts were assessable for responses and toxicity. The overall clinical RR were 45 % including 12.9 % partial responses (PR) and 6.4 % complete responses (CR) in ECF group and 69 % including 21.4 % PR and 4.7 % CR in ECX group. Median OS and TTP were 8.8 months (mos) ± 7.8 and 6.0 mos ± 4.4 in ECF group and 10.5 mos ± 7.2 and 7.0 mos ± 4.6 in ECX group respectively. The most frequent grade ¾ side effects graded according to CTCAE - 3 were fatigue - 20 % in ECF group and 19.5 % in ECX group, hematological (neutropenia) - 16 % in ECF group and 4.8 % in ECX group, nausea - 10 % in ECF group and 7.3 % in ECX group, diarrhea - 2.4 % in ECX group, hand- foot syndrome - 2.4 % in ECX group. Conclusions: ECX is at least effective as ECF with less toxic pattern and more convenient for pts and could replace ECF in first- line therapy in pts with advanced or metastatic gastric cancer. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16009-e16009 ◽  
Author(s):  
Prakash Peddi ◽  
Runhua Shi ◽  
Lori Panu ◽  
Fred Ampil ◽  
Cherie-Ann Nathan ◽  
...  

e16009 Background: SCHNC is a common malignancy and approximately 60% of patients present with locally advanced disease. There is paucity of data directly comparing Cx and CDDP with concurrent radiation in locally advanced SCHNC. We retrospectively reviewed charts of patients treated with CDDP and/or Cx along with radiation in locally advanced SCHNC comparing efficacy and outcomes in an academic cancer center. Methods: Ninety-five patients with locally advanced SCHNC were treated with concurrent CDDP (100 mg/m2 day 1, 22, 43) or Cx (400mg/m2 on day -7 and 250mg/m2 weekly) at our institution between January 2006 and June 2011. Forty-four patients were treated with CDDP (group A), 24 with Cx (group B) and 27 were initially started on CDDP but were switched to Cx secondary to toxicity (group C). All patients received concurrent radiation treatments (66-70 Gy, 2.0 Gy/fraction). The selection of CDDP versus Cx was largely based on ECOG performance status (PS) and baseline renal function of the patients. Chi-square test, analysis of variance, and log-rank test was used for analysis. The three groups had similar baseline characteristics except for mean age of 61, 56 and 55 years in group A, B and C respectively; T4 tumors consisted of 44%, 75% and 41% in groups A, B and C respectively. Groups A, B and C had a combined ECOG 0 and I (PS) of 93%, 75% and 92%. Patients with ECOG III PS were excluded. Results: Oropharynx was the most common treated site (38%) followed by Larynx (35%). Complete response (CR) was seen in 77%, 17% and 67% in groups A, B and C respectively (P<0.001). Median progression free survival (PFS) was 16.6, 4.3 and 22.8 in groups A, B and C respectively (P<0.001) and median overall survival (OS) was >35, 11.6 and >32 months in groups A, B and C respectively (P<0.0001). Conclusions: Concurrent CDDP with radiation leads to better response rate PFS and OS as opposed to Cx though many patients treated with CDDP could not complete treatment due to toxicity. Randomized trial comparing the two should be considered.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 26-26
Author(s):  
Torben Steiniche ◽  
Sun Young Rha ◽  
Hyun Cheol Chung ◽  
Jeanette Bæhr Georgsen ◽  
Morten Ladekarl ◽  
...  

26 Background: GEP and PD-L1 expression have been associated with anti–PD-1/PD-L1 therapy. In this retrospective observational study we explored the prognostic value of GEP and PD-L1 expression in pts with EC receiving standard-of-care therapy (SOC). Methods: Tumor tissue samples collected from 2005 to 2017 were procured from Yonsei Cancer Center (South Korea), Memorial Sloan Kettering Cancer Center (USA) and Aarhus University Hospital (Denmark). GEP score was derived from an 18-gene signature using extracted tumor RNA analyzed by NanoString nCounter; GEP high/intermediate (GEP-H/I) and low were defined by a cutoff of –1.540, consistent with pembrolizumab clinical trials. PD-L1 expression was assessed by PD-L1 IHC 22C3 pharmDx assay (Agilent); positive was defined as combined positive score (CPS) ≥ 10, where CPS is the the number of PD-L1–positive cells (tumor cells, lymphocytes and macrophages) divided by the total number of viable tumor cells, multiplied by 100. Associations of GEP score and PD-L1 expression with clinicopathologic variables were analyzed by chi-square test and multiple logistic regression models. Overall survival (OS) from diagnosis date to death date/last follow-up was analyzed using Cox proportional hazards models adjusting for age, sex, stage, region and ECOG performance status (PS). Results: 294 samples with both PD-L1 and GEP data were analyzed. Median age was 65 y (range 33-88); 85% were from men, 58% were stage IV, 63% were esophageal adenocarcinoma (EAC) and 37% were esophageal squamous cell carcinoma (ESCC). Overall 36% of tumors were GEP-H/I: 46% in EAC vs 18% in ESCC. GEP was not associated with OS overall (adjusted hazard ratio [aHR] –0.90; 95% CI 0.68-1.18) or in pts with EAC (aHR 0.93; 95% CI 0.68-1.27) or ESCC (aHR 0.76; 95% CI 0.40-1.44). 21% of tumors were PD-L1-CPS ≥ 10: 18% in EAC and 26% in ESCC. PD-L1 expression was associated with ECOG PS (adjusted odds ratio 0.520; 95% CI 0.309-0.875; P = 0.014) but was not associated with OS overall (aHR 0.89; 95% CI 0.64-1.24) or in pts with EAC (aHR 0.97; 95% CI 0.63-1.49) or ESCC (aHR 1.31; 95% CI 0.73-2.34). Conclusions: Our results suggest that T-cell–inflamed GEP and PD-L1 expression may not be prognostic in pts with EC who received SOC.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15599-e15599
Author(s):  
J. Yoon ◽  
S. Cho ◽  
W. Bae ◽  
J. Hwang ◽  
H. Shim ◽  
...  

e15599 Background: The role of the second line chemotherapy in advanced gastric cancer was not clear, but possibility of prolongation of survival is open question. Irinotecan is promising agents in gastric cancer and this phase II study evaluated the efficacy and safety of combination chemotherapy with irinotecan, high dose of 5-fluorouracil (5-FU) and leucovorin in taxane and cisplatin based chemotherapy refractory metastatic gastric cancer. Methods: Eligible criteria were as followed; histologic confirmed adenocarcinoma of stomach, previously treated with taxane and cisplatin, age≥18, Eastern Clinical Oncology Group (ECOG) performance status of 1 or less, adequate organ function. Irinotecan (150 mg/m2) as a 30-min infusion and leucovorin (200 mg/m2) as a 15-min infusion were given on day 1, followed by 5-FU 400 mg/m2bolus infusion then 5-FU 2,400 mg/m2 as a 48-hour continuous infusion. This cycle was repeated every 2 weeks until disease progression or unacceptable toxicities. Results: Thirty-four patients were enrolled. The median age was 57 years (range 27–73 years), and the ECOG performance status of all patients was 1. All patients were evaluable for safety and survival and twenty seven patients (79.4%) were evaluable for tumor response. The overall response rate was 18.5% (95% CI: 3.9–33.1). The median progression free survival and overall survival were 4.6 (95% CI: 2.4–6.9) and 9.3 months (95% CI: 5.2–13.4), respectively. Greater than grade 3 haematological toxicities were neutropenia in nine (26.5%), febrile neutropenia in one (2.9%) and thrombocytopenia in one patient (2.9%). The major non-haematological toxicity was asthenia, but most of patients showed grade 1 or 2. Greater than grade 3 non- haematological toxicities were elevated AST/ALT in four (11.8%), hyperbilirubinemia in two (5.9%), nausea in two patients (5.9%). Conclusions: This results showed that the combination chemotherapy with irinotecan, 5-FU and leucovorin was well tolerated and active in taxane and cisplatin refractory patients. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3051-3051 ◽  
Author(s):  
Yukiya Narita ◽  
Keiji Sugiyama ◽  
Seiichiro Mitani ◽  
Kazunori Honda ◽  
Toshiki Masuishi ◽  
...  

3051 Background: Anti-PD-1 monotherapy has proven effective for the patients (pts) with MGC. However, the identification of biomarkers for predicting clinical outcomes remain as critical needs. We aimed to identify baseline characteristics associated with time to treatment failure (TTF) or overall survival (OS) for anti-PD-1/PD-L1 monotherapy as second- or later-line therapy in MGC. Methods: Routine blood count parameters and clinical characteristics at baseline were retrospectively investigated in 31 pts with MGC in Aichi Cancer Center Hospital. Endpoints were TTF and OS following anti-PD-1/PD-L1 monotherapy. Kaplan-Meiyer and Cox regression analysis were applied for survival analyses. Results: Patient characteristics were as follows: median age (range), 68 (47–83); ECOG performance status (PS) 0/1, 21/10; PM +ve/-ve, 12/19; No. of metastatic sites 1–2/≥3, 18/13; No. of prior chemotherapy regimens 1–2/≥3, 11/20; and absolute eosinophil count (AEC) <150/≥150 /μl, 14/17. Objective response rate and disease control rate (RECIST ver. 1.1) were 26% vs. 0% (odds ratio [OR], 3.76; P = 0.12) and 79% vs. 50% (OR, 3.58; P = 0.12) in the PM -ve group (Cohort A) and the PM +ve group (Cohort B), respectively. On univariate analysis, the pts with poor PS, PM +ve, and high AEC were significantly poor TTF; and poor PS and PM +ve were significantly identified as prognostic factors of poor OS. On multivariate analysis, only PM +ve was independent negative impact not only for TTF but also for OS. Median TTF and OS were 5.4 vs. 1.3 months (M) (adjusted hazard ratio [HR], 4.29; 95%CI, 1.60–11.5; P < 0.01) and 28.2 vs. 7.5 M (adjusted HR, 3.68; 95%CI, 1.25–10.8; P = 0.02) in Cohort A and Cohort B. Six-months TTF probabilities of 42% vs. 0% ( P = 0.03) and one-year OS probabilities of 58% vs. 8% ( P< 0.01) were observed in Cohort A compared to in Cohort B. Conclusions: PM -ve in the pts treated with anti-PD-1/PD-L1 monotherapy was associated with better efficacy. In the pts with PM -ve, anti-PD-1/PD-L1 monotherapy could be adapted in first-line therapy. [Table: see text]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16034-e16034
Author(s):  
Jin Li ◽  
Shukui Qin ◽  
Lu Wen ◽  
Junsheng Wang ◽  
Wenying Deng ◽  
...  

e16034 Background: Apatinib, a small molecule multi-target tyrosine kinase inhibitor with high selectivity for VEGFR-2, has been approved for the treatment of advanced gastric cancer or gastroesophageal adenocarcinoma in China by significantly improving progression-free survival (PFS) and overall survival (OS). Here, we report safety and efficacy data from an open-label, single-arm, multicenter, phase IV trial of apatinib as a third-line or later line treatment for advanced gastric cancer. Methods: Eligible patients had histologically or cytologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma; and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; and adequate haematological and hepatic function; and failure of at least two lines of chemotherapy. Patients received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety, and secondary endpoints included PFS and OS. Results: The intention-to-treat population (ITT) included 2004 patients. At baseline, the median age was 59 (range, 19-85) years, ECOG performance status of 0/1/2 (%) was 15.4/68.8/15.1, and stage III/IV was 3.5/96.4; 98.8% had metastases, and among which metastatic foci≤2/ > 2 was 64.5/34.2 (%), respectively. 89.6% of the patients were given apatinib 500mg as the initial does and the median treatment duration was 56 days. After a median follow-up of 126.5 days, adverse events (AEs) occurred in 95.1% of the patients and 70.3% were grade ≥3. 87.9% of the patients experienced treatment-related AEs (TRAEs), of which 51% had grade ≥3, 12.3% and 16.8% reduced dose and discontinued the treatment, respectively. 57 (2.9%) TRAEs-related deaths were reported, mainly because of gastrointestinal bleeding (16 cases), upper gastrointestinal haemorrhage (7), cerebral haemorrhage (2), and gastric perforation (1). The incidence of TRAEs of special interest was 74.3%; 38.1% of patients developed grade≥3, mainly including hypertension (26.3%), bleeding (5.1%), proteinuria (4.5%), and hand-foot syndrome (3.1%). In an ITT population, median PFS was 2.7 months (95%CI 2.23-2.79) and median OS was 5.8 months (95% CI 5.42-6.11). Conclusions: This study confirms that apatinib has a well-established and manageable safety profile and survival benefit as third or later line therapy for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma. Clinical trial information: NCT02426034.


2020 ◽  
Author(s):  
Yongming Chen ◽  
Shuhang Xu ◽  
Chunyu Huang ◽  
Yihong Ling ◽  
Chengcai Liang ◽  
...  

Abstract Background: The relationship between gastric bare area adipose tissues invasion (GBAI) confirmed pathologically and the prognosis of gastric cancer (GC) patients is undefined. Till present, there hasn’t been literature investigating this phenomenon. Here, we aimed at analyzing the implication of GBAI in GC. Methods: The data of 1822 patients who underwent radical surgery between January 2000 and December 2013 at the Sun Yat-sen University Cancer Center were retrieved. Pathologically, tumor deposits (TDs) located >5mm from the leading edge of the primary tumor and the lymph nodes (LNs) station number 1, 2, 7, and 9 were considered as GBAI. Kaplan-Meier method, log-rank test and Cox’s proportional hazards model were employed to analyze. Results: 205 (11.3%) patients were pathologically diagnosed with GBAI, which was more commonly found in proximal or linitis lastica than distal GC (P<0.001). There was significant difference in 5-year survival between patients with and without GBAI for stages IIB, IIIA, IIIB, IIIC, respectively (P<0.009 for IIB, IIIA and IIIB, P=0.021 for IIIC). Among the 205 GBAI patients, 61 had detailed radiological follow-up data in which 26 (34.7%) were found to have retroperitoneal infiltration, 27 (36.0%) had peritoneal metastasis, 10 (13.3%) had hematogenous metastasis, 16 (21.3%) had lymphatic metastasis, and 16 (21.3%) had others. Conclusions: GBAI was identified as a predictor of unfavourable prognosis for GC and was more commonly found in the proximal or linitis plastica of the stomach than in distal stomach. Retroperitoneal infiltration was one of the most commonly identified metastatic route for GC associated with GBAI after radical surgery.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18646-e18646
Author(s):  
Laurence Vigouret-Viant ◽  
Clemence Legoupil ◽  
Aurelie Bardet ◽  
Celine Laurent ◽  
Michel Ducreux ◽  
...  

e18646 Background: For cancer patients, life-threatening complications may be difficult to anticipate, leading to complex medical decision-making processes. Since 2015, the Gustave Roussy Cancer Center has implemented a major institutional program including a Decision-Aid Form (ADF), outlining the anticipation of appropriate care for patient in case of worsening evolution. Methods: Between January and May 2017, all patients transferred from Site 1 to Site 2 of the hospital were prospectively included. In this study, we assessed the acceptability of the ADF, its using and its impact on the patient’s becoming. Results: Out of 206 patients included, 89.3% had an ADF. The planned stratification of care was notified in practically all cases. Conversely, the involvement of the palliative care team was notified in only 29% of the ADF. The value of the WHO/ECOG Performance Status was limited, varying between physicians. Finally, the field “information for patients and relatives” was insufficiently completed. Although a possible transfer to Intensive Care Unit was initially proposed in two-thirds of the patients, the majority (76%) of the 35 patients experiencing an acute event received exclusive medical or palliative care. The level of therapeutic commitment suggested by the ADF was never upgraded, and often revised towards less aggressive care, and especially without excess mortality for the patients who were initially designated to be eligible for intensive care. Moreover, the patient's survival at 6 months seems to be correlated with the anticipated level of care recorded on the FAD (Log-rank P value < 0,0001). Conclusions: The results of our study suggest that setting up a care stratification file in advance is possible in a French cultural setting and it could be helpful for clarifying prognosis assessment. To achieve complete acculturation, our extensive institutional program remains a cornerstone for the development of advance care planning. Since 2017, this program has widely spreaded ADF which is now integrated into the electronic medical record. Each physician can complete and modify the patient's ADF at any stage of the patient's disease course.


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