T-cell–inflamed gene expression profile (GEP) and PD-L1 expression in patients (pts) with esophageal cancer (EC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 26-26
Author(s):  
Torben Steiniche ◽  
Sun Young Rha ◽  
Hyun Cheol Chung ◽  
Jeanette Bæhr Georgsen ◽  
Morten Ladekarl ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Proportional Hazards ◽  
Performance Status ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
University Hospital ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Tissue Samples

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.

Retrospective multicenter cohort of nab-paclitaxel plus gemcitabine (NG) after FOLFIRINOX failure in advanced pancreatic cancer (APC): Effectiveness, tolerability, and response markers.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15743-e15743
Author(s):  
Ines Vendrell ◽  
Arlindo Rebelo Ferreira ◽  
Catarina Pulido ◽  
Anuraj Parmanande ◽  
Filipa Ferreira Da Silva ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Line Treatment ◽  
Ecog Performance Status ◽  
Ca 19.9

e15743 Background: NG is a standard 1st line treatment for APC. Although recommended in 2nd line after FOLFIRINOX, there is little evidence of its efficacy, tolerability and of markers of efficacy. Methods: We performed a multicenter retrospective cohort study, including patients (pts) with APC from 5 centers in Portugal treated with 2nd line NG after 1st line FOLFIRINOX from 01/2013-12/2016. We collected demographic, clinicopathological characteristics and treatment data. We used descriptive statistics, Kaplan-Meier methods and Cox proportional hazards analysis. Results: 30 pts were included; median age was 64 years (range 45–78); the majority had stage IV (90%) disease, an ECOG Performance Status of 0 (76.7%) and had received a median of 8.5 cycles of FOLFIRINOX (range 1–18). A median of 6 cycles of NG were administered (range 1–13). Median progression free survival (PFS) and overall survival (OS) were 6.4 months (CI 95% 3.0-8.5) and 11.4 months (CI 95% 8.4–16.5), respectively, and did not differ by age < 65 or ≥65 (p = 0.87; p = 0.57 respectively). The most frequent toxicity was fatigue (66.6%, any grade). Grade 3-4 events occurred in 40% of pts – thrombocytopenia in 16.7%, neutropenia in 10.0%; anemia, sensorial neuropathy, fatigue and diarrhea each occurred in 3.3% of patients. No febrile neutropenia events or toxic deaths occurred. Median CA 19.9 at the beginning of NG was 1254U/mL (IQR: 207–6775); the median decrease of CA19.9 at 3 months was 45U/mL (IQR:-1373– +174). CA 19.9 variation at 3 months did not correlate with PFS (p = 0.53) or OS (p = 0.09) in multivariate analysis (adjusted for age and stage at diagnosis). Neutrophil to Lymphocyte ratio (NLR) was high ( > 3.0) in 37.5% of patients before 1st line treatment and in 27.6% at the beginning of NG. In multivariate analysis NLR before 1st or 2nd chemotherapy lines were not associated with PFS (p = 0.39; p = 0.14 respectively) or OS (p = 0.44; p = 0.12, respectively). Conclusions: In this cohort of pts with APC, NG was an effective and well tolerated 2nd line regimen after FOLFIRINOX failure, even in pts ≥65 years. Neither CA19.9 variation at 3 months nor NLR were markers of NG clinical benefit.

scholarly journals Exploring the prognostic value of the neutrophil-to-lymphocyte ratio in cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rachel Howard ◽  
Peter A. Kanetsky ◽  
Kathleen M. Egan
Keyword(s):  
Prognostic Value ◽  
Clinical Characteristics ◽  
Proportional Hazards ◽  
Area Under The Curve ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Neutrophil To Lymphocyte Ratio ◽  
Cancer Center ◽  
Lymphocyte Ratio ◽  
Patient Subgroups

AbstractIn cancer patients, a high pre-treatment neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival outcomes. Significant variation in the magnitude of this association has been observed between studies, but sources of this variation are poorly understood. Here, we explore differences in the prognostic potential of NLR between patient subgroups stratified by demographic and clinical characteristics using a retrospective cohort of 5,363 patients treated at Moffitt Cancer Center (Tampa, FL). We identify patients for whom NLR has maximum prognostic potential via adjusted hazard ratios (HRs) calculated using multivariable Cox proportional hazards models and area under the curve analysis. NLR demonstrates stronger associations (HRs > 2) with survival among African-American patients, patients receiving radiation therapy, stage IV patients, and melanoma patients when compared with the overall study population (HR = 1.58). Sensitivity and specificity of NLR as a prognostic marker are also higher in these patient subgroups, and increase further with combinations of multiple “high-risk” demographic or clinical characteristics. In summary, NLR may have greater prognostic value in patients with certain demographic and clinical features. Future prospective studies could validate this hypothesis, after further characterization of populations in which NLR has maximum prognostic potential and the identification of meaningful thresholds for risk stratification.

Patterns of referral to palliative care in clinical practice in patients with stage IV non-small cell lung cancer.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 39-39
Author(s):  
Safiya Karim ◽  
Shahid Ahmed
Keyword(s):  
Palliative Care ◽  
Clinical Practice ◽  
Cox Regression ◽  
Smoking Status ◽  
Performance Status ◽  
Stage Iv ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Logistic Regression Models ◽  
Symptomatic Disease

39 Background: Recent evidence has shown that patients with stage IV NSCLC benefit from early referral to palliative care (PC). In August 2010, a landmark randomized control trial revealed that patients with advanced NSCLC, who received early PC, had better quality of life, mood and survival (NEJM 2010; 363:733-42). Our study aimed to determine pattern of PC referral in clinical practice, in patients with stage IV NSCLC before and after the publication of the trial, and to assess factors correlated with PC referral. Methods: The study population was comprised of a cohort of patients with stage IV NSCLC, diagnosed between 2009 and 2011, and referred to the Saskatoon Cancer Center. Logistic regression models were used to assess factors correlated with PC referral. Kaplan Meier method was used to estimate survival. Cox regression analyses were used to determine factors correlated with survival. Results: 215 patients with median age of 68 yrs (range: 40-92) and M:F of 108:107 were identified. 101 (47%) patients had comorbid illness, 100 (47%) had ECOG performance status <2, 136 (63%) were married/common law and 161 (75%) had symptomatic disease. 126/251 (58%) were referred to PC. 70/118 (59%) diagnosed before Sep 2010 were referred to PC compared with 56/97 (58%) diagnosed after Sep 2010 (p=NS). The median time to PC referral from date of diagnosis was 51 days (inter-quartile range: 19-155). 33% patients were referred within 4 wks of diagnosis. Symptomatic disease (odd ratio [OR]=3.7, 95% CI =1.8-7.5), bone metastasis (OR = 3.0, 95% CI = 1.6-5.6), and brain metastasis (OR=2.2, 95% CI =1.1-4.5) were correlated with referral to PC. Median survival of whole cohort was 4 months (95% CI: 3.1-4.8). 2nd or 3rd line therapy (Hazard ratio [HR]= 0.54, 95% CI:0.34-0.87), non-smoking status (HR= 0.58, 95% CI:0.38-0.87), chemotherapy (HR 0.64, 95% CI:0.46-0.89), and lack of symptoms (HR=0.68, 95%CI:0.48-0.96) were correlated with better survival. Conclusions: Our study shows that publication of the landmark trial did not influence the pattern of referral to PC at our center. Symptomatic patients and those with metastasis to brain or bone were more often referred to PC. No survival benefit was seen in patients who were referred to PC.

Outcomes for patients ≥75 years with localized gastroesophageal cancer: Experience from the Princess Margaret Cancer Centre.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 189-189
Author(s):  
Akina Natori ◽  
Bryan Chan ◽  
Hao-Wen Sim ◽  
Eric Xueyu Chen ◽  
Geoffrey Liu ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Significant Survival ◽  
Comorbidity Index ◽  
Cancer Experience

189 Background: The optimal treatment and outcome for elderly patients (pts) with localized gastroesophageal (GE) cancer remains unclear as they are underrepresented in clinical trials. We aimed to assess survival in pts ≥ 75 years according to treatment received. Methods: A retrospective analysis was performed for all pts aged ≥ 75 years with GE cancer treated in 2012 and 2013. Frailty was measured using the Charlson comorbidity index (CCI) and ECOG performance status (PS). Overall survival (OS) and disease-free survival (DFS) were assessed via uni- and multivariable Cox proportional hazards regression, adjusting for demographics. Logistic regression analyses were used to examine factors impacting treatment choices. Results: Of 70 pts, median age was 82 years (range: 75-98), primary sites were esophageal (40%, with 61% squamous histology), GE junction (24%) and gastric (36%). Baseline characteristics included: PS: 0 (40%), 1 (39%), 2 (14%), 3 (7%); and CCI: 0 (36%), 1 (20%), 2 (21%), ≥ 3 (23%). Treatment received included surgery (33%), radiotherapy (RT) (31%); surgery plus adjuvant chemotherapy (chemo) and/or RT (9%); chemoradiation alone (7%) and 20% had no active treatment. In univariable analysis; age < 85 (p = 0.007) and surgery (p = 0.022) were associated with improved OS. Chemo and RT, either alone or in combination, did not significantly improve OS. In multivariable analysis; age < 85 (HR 0.46, 95% CI: 0.23-0.94, p = 0.034), surgery (HR 0.32, 95% CI: 0.14-0.74, p = 0.008) and CCI < 2 (HR 0.52, 95% CI: 0.27-0.99, p = 0.048) were identified as independent predictors for improved OS. Age ≥ 85 was significantly associated with omission of surgery (OR 3.61, 95% CI: 1.13-14.01, p = 0.041) but in contrast, PS ≥ 2 (p = 0.475) and CCI ≥ 2 (p = 0.939) were not predictive. Conclusions: At our institution, very few pts ≥ 75 years received multimodality therapy for localized GE cancers. Surgery was the only treatment modality associated with a significant survival advantage, and additional chemo and/or RT did not further improve OS. The only predictor for having surgery was age. Consequently, future studies should consider comprehensive assessment for surgery so that eligible elderly pts can benefit.

Survival outcomes for de novo versus relapsed stage IV gastric and gastroesophageal junction (GEJ) adenocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 148-148
Author(s):  
Bryan Anthony Chan ◽  
Hao-Wen Sim ◽  
Akina Natori ◽  
Stephanie Moignard ◽  
Daniel Yokom ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
De Novo ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Tumor Biology ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Survival Outcomes ◽  
Primary Therapy ◽  
Metastatic Relapse

148 Background: In gastric/GEJ cancer, 40% of patients (pts) are metastatic at diagnosis ( de novo stage IV) and up to 70% with locoregional disease recur (relapsed stage IV). We compared survival outcomes between de novo vs relapsed stage IV. Methods: A retrospective observational study of stage IV gastric/GEJ pts was conducted (2012-2015). Overall survival (OS) was from date of stage IV diagnosis. PFS1 defined the period from stage IV diagnosis to first progression. PFS2 was from first to second progression. For relapsed stage IV pts, disease-free interval (DFI) was the period from initial diagnosis to metastatic relapse. Cox proportional hazards models compared OS, PFS1 and PFS2 between de novo vs relapsed stage IV pts, stratified by DFI [ < 6, 6-12 and > 12 months (mo)] and controlled for baseline patient characteristics. Results: Of 198 pts, 62% were male and median age was 64 years (26-93), with 64% gastric and 36% GEJ adenocarcinomas. Primary therapy for locoregional pts included surgery (75%), perioperative chemotherapy (42%) and radiotherapy (42%). De novo and relapsed stage IV pts represented 68% and 32% of the cohort respectively. Median follow-up was 13 mo. Controlled for age, performance status and Charlson comorbidity index, there were no significant differences in OS (median OS 12.5 ( de novo) vs 12.2 mo (relapsed); HR 1.22, 95% CI 0.83-1.77, p = 0.31), PFS1 (6.8 vs 7.4 mo; HR 1.00, 95% CI 0.65-1.56, p = 0.98) or PFS2 (3.8 vs 3.0 mo; HR 1.03, 95% CI 0.44-2.41, p = 0.95). Median OS for relapsed stage IV patients were different by DFI groups (log-rank p = 0.02): 22.9 mo (for DFI > 12mo; n = 31), 11.2 mo (DFI 6-12; n = 19) and 7.5 mo (DFI < 6; n = 14). Additionally, OS was significantly better if the DFI was greater than 12 mo, compared with de novo stage IV (HR 0.50, 95% CI 0.28-0.88, p = 0.02). Conclusions: There was no observed difference in the natural history of de novo vs relapsed stage IV gastric/GEJ pts. DFI was strongly prognostic with median OS (from date of relapse) approaching 2 years for relapsed pts with DFI > 12 mo. In addition to implications for treatment strategy, tumor biology within subgroups should be examined to identify novel biomarkers and potential therapeutic targets.

Does up-front definitive surgical resection with delayed chemotherapy in patients with stage IV rectal cancer compromise overall survival?

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 586-586
Author(s):  
Bindu V. Manyam ◽  
Shlomo A. Koyfman ◽  
Davendra Sohal ◽  
Ismail Mallick ◽  
Chandana A. Reddy ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Surgical Resection ◽  
Proportional Hazards ◽  
Performance Status ◽  
Rectal Adenocarcinoma ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Significant Difference ◽  
Poorly Differentiated

586 Background: Definitive resection of the primary is frequently part of the management of patients (pts) with stage IV rectal cancer with good performance status and low volume of systemic metastases. It is unclear whether delaying systemic therapy for up front surgical management of the primary compromises overall survival (OS). Methods: Pts with metastatic rectal adenocarcinoma who received definitive surgical resection between 1998-2011 were identified in an IRB approved registry. The sequencing of CT and surgery, and the use of perioperative radiation therapy (RT), was at the discretion of treating physicians. Preoperative chemotherapy (Pre-CT) regimens included 5-fluorouracil (5-FU) +/- leukovorin (LV), capecitabine, 5-FU/LV/oxaliplatin +/- avastin, or 5-FU/LV/irinocetan. RT dose was typically 50.4 Gy. OS was measured from the date of diagnosis. Baseline variables were compared using the Chi-square and unpaired t-tests. OS was calculated using the Kaplan Meier method. Univariate (UVA) and multivariate analysis (MVA) were performed using Cox proportional hazards regression to identify variables associated with OS. Results: In this study of 115 pts, 75 (65%) were treated with pre-CT, while 40 (35%) were treated with up front surgery. Of the pts who received surgery up front, 3 (8%) received RT and of the pts who received pre-CT, 62 (83%) received RT. The cohort was predominantly male (70%) with a median age of 57, median KPS of 80, and median follow-up of 24.1 months. 94% of pts had T3/T4 tumors, 80% had N+ disease, and 33% had poorly differentiated tumors. Liver directed therapy (LDT) was performed in 61% of pts. There was no significant difference in OS (32.3 vs. 32 months; p = 0.24) between pts treated with pre-CT and those who received surgery up front, respectively. UVA demonstrated that pre-CT was not associated with OS (HR 1.26; p = 0.544). MVA demonstrated that pts with poorly differentiated tumors (HR 2.04; p = 0.007) and those that did not undergo LDT (HR 2.45; p = 0.001) had inferior survival. Conclusions: Delaying systemic chemotherapy in order to achieve local control with surgical resection up front does not appear to impact OS in pts with stage IV rectal cancer.

Outcomes for patients ≥75 years with localized gastroesophageal cancer: Experience from the Princess Margaret Cancer Centre.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10037-10037
Author(s):  
Akina Natori ◽  
Bryan Anthony Chan ◽  
Hao-Wen Sim ◽  
Lucy Xiaolu Ma ◽  
Daniel Yokom ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Optimal Treatment ◽  
Gastric Disease ◽  
Ecog Performance Status ◽  
Disease Site ◽  
Radiotherapy Alone ◽  
Cancer Experience

10037 Background: The optimal treatment and outcome for elderly patients (pts) with localized gastroesophageal (GE) cancer remains unclear as they are underrepresented in clinical trials. We aimed to assess survival in pts ≥75 years according to treatment received. Methods: A retrospective analysis was performed for all pts aged ≥75 years with GE cancer treated in 2012-2014. Frailty was measured using the Charlson comorbidity index (CCI) and ECOG performance status (PS). Overall survival (OS) and disease-free survival (DFS) were assessed via uni- and multivariable Cox proportional hazards regression, adjusting for demographics. Logistic regression analyses were used to examine factors impacting treatment choices. Results: Of 105 pts, median age was 81 years (range: 75-99), primary sites were esophageal (55%, with 43% squamous histology) and gastric (45%). Baseline characteristics included: PS: 0 (31%), 1 (42%), 2 (16%), 3 (10%), 4 (1%); and CCI: 0 (34%), 1 (25%), 2 (19%), ≥3 (22%). Treatment received included radiotherapy alone (RT) (31%); surgery alone (29%); surgery plus adjuvant chemotherapy (chemo) and/or RT (14%); chemoradiation alone (7%) and supportive care (18%). In univariable analyses; age < 85 (p = 0.003), PS < 2 (p = 0.03) and surgery (p < 0.001) were associated with improved OS. Chemo and RT, either alone or in combination, did not significantly improve OS. In multivariable analyses; surgery (HR 0.38, 95% CI 0.21-0.70, p = 0.002) was the only independent predictor for improved OS. Patients with good PS (p = 0.01), gastric disease site (p = 0.01) and adenocarcinoma histology (p = 0.02) were more likely to undergo surgery. Conclusions: At our institution, relatively few pts ≥75 years received multimodality therapy for localized GE cancers. Those pts ≥75 years who underwent surgery had excellent outcomes, but they were well-selected. Comprehensive assessment should be considered for pts ≥75 years with localized GE cancer to ensure optimal treatment selection, particularly given the potential benefit of surgery.

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 ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
South Korea ◽  
Tumor Cells ◽  
Performance Status ◽  
Metastatic Gastric Cancer ◽  
Rank Test ◽  
Cancer Center ◽  
Immune Gene ◽  
Ecog Performance Status ◽  
Percentage Survival

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.

Comparison of outcomes with pembrolizumab monotherapy (P) versus combination with chemotherapy (P+C) in advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21579-e21579
Author(s):  
Kartik Sehgal ◽  
Ritu R. Gill ◽  
Poorva Bindal ◽  
Anita Geevarghese Koshy ◽  
Danielle C McDonald ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Advanced Nsclc ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Performance Status ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Ecog Performance Status

e21579 Background: P and P+C are standard-of-care (SOC) treatment options for advanced NSCLC. However, they have not yet been directly compared in clinical trials. Methods: We conducted a retrospective cohort study of patients with advanced NSCLC who initiated treatment with SOC P±C at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. All radiographic scans were independently evaluated by a thoracic radiologist using iRECIST. Survival time was defined from the start of P±C. Kaplan-Meier and Cox proportional hazards model were utilized. Results: Of 103 patients with median follow up of 17.7 months, 74 (71.8%) had received P, while 29 (28.2%) had received P+C. In PD-L1 tumor proportion score (TPS) unselected population, there were no significant differences in age, sex, smoking status, driver mutation, tumor mutational burden (TMB), line of therapy, ECOG performance status (PS) or immune-related adverse events (irAE) between P and P+C groups. 71.6% in P vs 13.8% in P+C had PD-L1 TPS ≥50% (p < 0.001). There were no significant differences between the two groups in objective response rate (ORR), disease control rate (DCR), unadjusted progression-free survival (PFS) or unadjusted overall survival (OS) (Table). Multivariable adjustment for confounding factors between P+C vs P revealed no differences in OS [hazard ratio (HR) for death, 1.53, 95% CI 0.55 – 4.25] or PFS [HR for progression/death, 1.75, 95% CI 0.63 – 4.91]. Further stratification into PD-L1 TPS ≥50% and < 50% showed no significant differences between P+C vs. P in adjusted OS [HR for death, TPS < 50%- 1.54 (95% CI 0.59 – 4.03); TPS ≥50%- 0.71 (95% CI 0.11 – 4.52)] or PFS [HR for progression/death, TPS < 50%- 1.58 (95% CI 0.72 – 3.48); TPS ≥50%- 0.64 (95% CI 0.06 – 6.93)]. ECOG PS and development of irAE influenced OS in all groups, while TMB was relevant in PD-L1 ≥50% only. Conclusions: Our study shows no significant differences in outcomes with P vs P+C in advanced NSCLC in a real-world setting, albeit with limitations of single-center design, limited sample size, different line settings and lack of disease burden stratification. Ongoing phase III trials comparing front line P vs P+C will definitively address the long-term clinical benefits -if any- of combining cytotoxic chemotherapy with anti-PD-1 drugs. [Table: see text]

Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 507-507 ◽  
Author(s):  
Kimmie Ng ◽  
Alan P. Venook ◽  
Kaori Sato ◽  
Bruce W. Hollis ◽  
Donna Niedzwiecki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Prognostic Factors ◽  
Proportional Hazards ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Blood Draw ◽  
Ecog Performance Status

507 Background: Prospective epidemiologic data suggest that higher levels of 25-hydroxyvitamin D [25(OH)D] are associated with improved survival in patients with colorectal cancer (CRC), however, the relationship between 25(OH)D and outcome in metastatic CRC, specifically, is unknown. Methods: We prospectively assessed the association between plasma 25(OH)D and overall survival (OS) in previously untreated metastatic CRC patients enrolled in CALGB 80405, a randomized phase III trial of chemotherapy + bevacizumab, cetuximab, or both, prior to the KRAS WT amendment. Progression-free survival (PFS) was a secondary endpoint. Plasma 25(OH)D levels were measured at baseline by radioimmunoassay, and dietary and lifestyle behaviors collected from self-administered questionnaires. Cox proportional hazards models were used to calculate hazard ratios adjusted for other prognostic factors. In sensitivity analyses, patients who died within 3 or 6 months of blood draw were excluded to address the possibility of reverse causation. Results: Among 1,043 patients, median plasma 25(OH)D was 17.2 ng/mL (range 2.2-72.7). Older and black patients, those with lower dietary and supplemental vitamin D intake, ECOG performance status 1 (vs. 0), higher body-mass index, lower physical activity, and blood draws during the winter and spring had significantly lower levels of 25(OH)D. Patients in the highest quintile of 25(OH)D had significantly improved OS compared to those in the lowest after adjusting for pathologic and clinical prognostic factors (median 32.6 vs. 24.5 months; HR 0.67, 95% CI, 0.53-0.86; p trend 0.002). Increasing concentrations of 25(OH)D were also associated with improved PFS (median 12.2 vs. 10.1 months; HR 0.80, 95% CI, 0.64-1.01; p trend = 0.02). The results were consistent across subgroups of patient characteristics, including KRAS status, and remained unchanged after excluding patients who died within 3 or 6 months of blood draw. Conclusions: Higher concentrations of plasma 25(OH)D are associated with significantly improved survival in metastatic CRC patients treated with chemotherapy + biologics. Randomized trials of vitamin D supplementation are warranted and are currently underway.

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