532 Background: Early mortality is a major problem in colorectal cancer and our understanding of ... more 532 Background: Early mortality is a major problem in colorectal cancer and our understanding of risk factors and predictors is incomplete. A venous thromboembolism (VTE) Risk Score, comprising primary site, baseline hemoglobin, leukocyte and platelet counts, and body mass index [Khorana et al, Blood, 2008], has been shown to be associated with early mortality in solid tumors [Kuderer et al, 2008; Ay et al, 2013]. We evaluated the value of this Risk Score and other key prognostic variables in predicting early mortality for colorectal cancer (CRC) patients. Methods: CANTARISK was a prospective, non-interventional, global cohort study in patients with CRC and lung cancer initiating a new chemotherapy regimen. Clinical data were collected at 0, 2, 4, and 6 months. All data were compiled centrally and analyzed after the study closed. Risk score categories were as defined previously [Blood, 2008]. Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted odds ratios (OR) are presented. Results: A total of 1,789 CRC patients were enrolled from 2011-12; data on 1,533 evaluable patients are presented. Median age was 62 years; 71% were Caucasian. Geographic distribution was Europe 37%, North America 28%; Asia 23%; South America 12%. One-third (33%) had a rectal primary and 65% had metastatic disease. There were 184 deaths (10.3%) on study. For low, intermediate and high Risk Score, there were 8.1%, 11.2%, and 32.5% deaths, respectively. In multivariate analyses, the Risk Score remained an independent predictor of death (OR for high/intermediate vs. low score = 1.70, p = 0.0027), in addition to age (OR for each incremental year = 1.03, p = 0.0014), presence of metastatic disease (OR = 3.28, p < 0.0001), and ECOG performance status ≥2 (OR = 3.85, p < 0.0001). VTE itself was not associated with death. Conclusions: This prospective global cohort study demonstrates that the Risk Score is prognostic of early mortality in CRC patients, in addition to age, stage, and performance status. Intermediate or high-risk patients, as defined by the Risk Score, may benefit from additional interventions aimed at reducing early mortality.
During a 6-year period (1977 to 1982) blood samples from 152 Canadian patients were referred to t... more During a 6-year period (1977 to 1982) blood samples from 152 Canadian patients were referred to the national reference laboratory of the Canadian Red Cross Society because the referring hospitals had not been able to determine the cause of the patients' severe nonhemolytic transfusion reactions. Twenty-one patients were found to be IgA deficient, and 12 of them had strong class-specific anti-IgA antibodies, which were presumed to have been responsible for the reactions. The spectrum of symptoms that accompanied these violent reactions was documented for 10 of the patients. As a probable minimum, the incidence of anti-IgA-mediated reactions averaged 1.3 per million units of blood or blood products transfused during this period.
BACKGROUND: Patients with lung cancer are known to be at increased risk for venous thromboembolis... more BACKGROUND: Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). However, there have been few studies of risk factors for VTE in lung cancer patients undergoing systemic chemotherapy. METHODS: CANTARISK was a prospective, non-interventional, global cohort study including patients with lung cancer initiating a new chemotherapy regimen. Clinical data were collected at baseline and at 2, 4 and 6 months follow-up. The impact of patient-, disease- and treatment-related factors on the occurrence of VTE in the first 6 months was evaluated in univariable and multivariable Cox regression analyses. RESULTS: A total of 1,980 patients with lung cancer were enrolled from 2011-12 of which 84% were diagnosed with non-small cell lung cancer (NSCLC). Median age was 63 years (range, 25-91) and 63% were male while 82% were active or former smokers. Race was white (70%), Asian (22%), or black (4%) with similar numbers from North America, Europe, and other regions including Asia. Metastatic disease was reported in 70% and ECOG PS was ≥2 in 13%. During the first six months, 121 patients developed a VTE (6.1%), of which 47.1% had pulmonary embolism (PE), 45.5% deep venous thrombosis (DVT), 3.3% catheter-associated thrombosis, and 4.1% visceral thrombosis. Among significant factors in univariable analysis, independent predictors for VTE in multivariable Cox regression analysis included female gender, US geographic region, leg immobilization, and presence of a central venous catheter (Table) with a trend toward greater risk for higher grade histology. Although predictive of early all-cause mortality in this study population (Kuderer et al ASCO 2016), the previously validated risk score for VTE in ambulatory cancer patients (Khorana et al: Blood 2008) was not significantly associated with VTE in either univariable or multivariable analysis. CONCLUSIONS: Several demographic, geographic, and clinical factors are significantly associated with an increased risk of VTE in patients with lung cancer receiving systemic chemotherapy. Future analysis will attempt to assess how novel targeted treatment options might impact the Khorana score's predictive ability across all lung cancer patients. Disclosures Kuderer: Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Lyman:Amgen: Research Funding. Khorana:Bayer: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Halozyme: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.
BACKGROUND Venous thromboembolism (VTE) is an important complication among patients with colorect... more BACKGROUND Venous thromboembolism (VTE) is an important complication among patients with colorectal cancer but its prevalence and predictors are incompletely understood. The Khorana Score (KS), comprising primary site, baseline hemoglobin, leukocyte and platelet counts, and body mass index [Khorana et al, Blood, 2008], has been demonstrated to predict VTE in various cancer settings. We evaluated the value of this Score and other key prognostic variables in a global prospective cohort study to define the incidence, predictors and consequences of VTE in patients undergoing adjuvant or palliative chemotherapy for colorectal cancer. METHODS CANTARISK was a prospective, non-interventional, international cohort study in patients with lung and colorectal cancer on chemotherapy; data for the colorectal cohort are presented here. Clinical data were collected at baseline, and at 2, 4 and 6 months. All data were compiled centrally and analyzed after the study had closed. KS categories were as defined previously [Blood, 2008]. Statistically significant univariable associations and a priori variables were tested in multivariable models; adjusted odds ratios (OR) with confidence intervals (CIs) are presented. RESULTS A total of 1,789 patients with colorectal cancer were enrolled from 2011 to 2012. Median age was 62 years; 61% were male; 71% were Caucasian; 18% were Asian; 37% were from Europe, 28% from North America, 23% from Asia, and 12% from South America. During the six-month follow-up period, 92 (5.1%) patients experienced VTE events; 18 patients experienced 2 events each, and 2 patients experienced 3 events each, for a total of 112 VTE events. Of these 112 events, 69 (61.6%) were deep venous thromboses (DVT), 22 (19.6%) were pulmonary emboli (PE), 14 (12.5%) were catheter-associated thrombi, and 7 (6.3%) were visceral thrombi. The majority (n=94, 83.9%) were symptomatic. For low, intermediate, and high KS, there were 4.3% (n=42), 6.8% (n=39), and 12.5% (n=5) VTE events, respectively (N=1596 due to some missing values for KS components). In adjusted multivariable analyses, KS (OR for high/intermediate vs. low = 1.82, 95% CI = 1.15-2.87), ECOG performance score (OR for 2/3/4 vs. 0/1 = 2.17, 95% CI=1.07-4.43), and central venous catheter (OR for yes vs. no = 4.01, 95% CI=2.32-6.94) were independent predictors of VTE. Notably, age, metastatic (vs. non-metastatic) disease, surgery or immobilization within the prior 6 months, current smoking, and history of VTE were not associated with new VTE events. CONCLUSIONS This global prospective study demonstrates that VTE events are prevalent among patients with colorectal cancer receiving systemic chemotherapy. Khorana Score category is a strong predictor of risk. Ongoing clinical trials are focusing on the benefit of prophylactic anticoagulation in high-risk patients in these settings. Disclosures Kuderer: Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Lyman:Amgen: Research Funding. Khorana:Amgen: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.
9078Background: There are few studies of factors associated with early mortality in patients with... more 9078Background: There are few studies of factors associated with early mortality in patients with lung cancer in a real world setting. Preliminary studies of a risk score for venous thromboembolism...
558 Background: Bleeding is an important complication among patients with colorectal cancer but i... more 558 Background: Bleeding is an important complication among patients with colorectal cancer but its prevalence and predictors are incompletely understood. We evaluated data from a global prospective cohort study to define the incidence, predictors and consequences of bleeding in patients undergoing adjuvant or palliative treatment for colorectal cancer. Methods: CANTARISK was a prospective, non-interventional, international cohort study in patients with lung and colorectal cancer on chemotherapy, the patients were not on long term anticoagulation. Clinical data were collected at baseline, and at 2, 4, and 6 months. All data were compiled centrally and analyzed after the study had closed. Statistically significant univariable associations and a priori variables were tested in multivariable models; adjusted odds ratios (OR) with confidence intervals (CIs) are presented. Results: A total of 1,789 patients with colorectal cancer were enrolled from 2011-12. Median age was 62 years; 61% were male; 71% were Caucasian and 18% were Asian; 37% were from Europe, 28% from North America, 23% from Asia, and 12% from South America. Ninety-two (5.14%) patients experienced at least one bleeding episode during antineoplastic treatment, ranging from 1 to 5 episodes each, with a total of 109 episodes. The gastrointestinal tract was the source in 49 (45%) episodes. Approximately one-third of episodes (n=34, 31%) necessitated transfusion, but only 1 (0.9%) was fatal. In multivariate analysis, independent predictors of bleeding included presence of metastases (OR = 2.13, 95% CI=1.25-3.65) and surgery within prior 6 months (OR = 3.66, 95% CI=1.78-7.47) but not intact primary tumor (OR = 1.57, 95% CI=0.99-2.51). Notably, age, baseline blood counts, ECOG performance score, and anticoagulant use during study were not associated with bleeding. Conclusions: Bleeding is prevalent amongst patients with colorectal cancer receiving systemic chemotherapy. Post-surgical patients and those with metastatic disease appear to be at highest risk. Resection of the primary tumor does not appear to significantly alter risk.
Despite high initial response rates, most patients with small cell lung cancer (SCLC) relapse sho... more Despite high initial response rates, most patients with small cell lung cancer (SCLC) relapse shortly after discontinuing therapy, and cure remains an elusive goal, even for patients with limited-stage disease. For this reason, investigators have turned to the evaluation of alternative treatment strategies for patients with this malignancy. Interferon has been evaluated in four trials of adjuvant therapy after response to chemotherapy for SCLC. Different interferon preparations were used, but none of the trials showed a significant prolongation of survival. Tumor vaccines against gangliosides that are expressed on almost all human SCLC cells have been recently developed. An anti-idiotypic monoclonal antibody against the GD3 ganglioside, BEC-2, is being evaluated after chemotherapy in SCLC patients in a European study. In North America, a bivalent ganglioside vaccine, BMS-248967, is under study at the phase II level. If results are promising, a phase III trial will be undertaken. Trials of anticoagulant therapy using heparin, warfarin, and aspirin were undertaken in the 1980s and early 1990s. Although one study of warfarin and another of heparin showed trends in favor of anticoagulant therapy, there has been little research over the past decade evaluating this form of treatment of SCLC. The matrix metalloproteinase inhibitors marimastat and BMS-275291 are under evaluation in SCLC. In all trials, the matrix metalloproteinase inhibitor is administered after chemotherapy and radiotherapy as adjuvant treatment. These trials are not yet mature and survival results are not available. Miscellaneous treatments, including monoclonal antibody therapy, tamoxifen, and growth factor inhibition have not yet been shown to have a role in the treatment of SCLC. Semin Oncol 28 (suppl 4):30-37.
Background Patients with lung cancer are known to be at increased risk for venous thromboembolism... more Background Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). Venous thromboembolism is associated with increased risk for early mortality. However, there have been no studies performing a comprehensive assessment of risk factors for VTE or early mortality in lung cancer patients undergoing systemic chemotherapy in a global real-world setting. Materials and Methods CANTARISK is a prospective, global, noninterventional cohort study including patients with lung cancer initiating a new cancer therapy. Clinical data were collected until 6-month follow-up. The impact of patient-, disease-, and treatment-related factors on the occurrence of VTE and early mortality was evaluated in univariable and multivariable Cox regression analyses. A previously validated VTE risk score (VTE-RS) was also calculated (also known as Khorana score). Results Of 1,980 patients with lung cancer who were enrolled from 2011 to 2012, 84% had non-small cell lung cancer. D...
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jan 22, 2018
Anti-PD1/PD-L1 immunotherapy has demonstrated success in the treatment of advanced non-small cell... more Anti-PD1/PD-L1 immunotherapy has demonstrated success in the treatment of advanced non-small cell lung cancer (NSCLC). Recently, PD1/PD-L1 blockade also has demonstrated interesting results in small trials of neo-adjuvant treatment in Stage IB-IIIA NSCLC. In addition, several clinical trials using anti-PD1/PD-L1 as an adjuvant or neo-adjuvant treatment in resectable stage NSCLC patients are ongoing. However, few analyses of anti-PD1/PD-L1 immunotherapy related biomarkers in early stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early stage SqCLC, providing data for identifying the potential role for anti-PD1/PD-L1 treatment in early stage SqCLC patients. A total of 255 early stage SqCLC patient specimens were identified within the Strategic Partnering to Evaluate Cancer Signatures (SPECS) program participating centers. PD-L1 protein expression by I...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 13, 2017
Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed d... more Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response E...
We investigated the safety and antitumor activity of dalotuzumab, a selective anti-insulin growth... more We investigated the safety and antitumor activity of dalotuzumab, a selective anti-insulin growth factor 1 receptor monoclonal antibody (IGF1R MoAb), plus erlotinib in a sequential phase I/II trial in unselected patients with refractory advanced non-small-cell lung cancer (NSCLC).The phase I trial determined the recommended dose and safety of erlotinib plus dalotuzumab at 5 mg/kg or 10 mg/kg weekly in 20 patients. The phase II trial compared outcomes to erlotinib alone and erlotinib plus dalotuzumab at the mg/kg established in the phase I trial. Erlotinib at 150 mg plus dalotuzumab at 10 mg/kg was safe. The phase II trial included 37 patients in the erlotinib arm and 38 patients in the erlotinib plus dalotuzumab arm. Progression-free survival was 1.6 versus 2.5 months, overall survival was 10.2 and 6.6 months, and the objective response rate was 7.9% and 2.7%, respectively, with no significant differences between the two arms. Grade 3-5 adverse events occurred in 11 (28.9%) versus 1...
532 Background: Early mortality is a major problem in colorectal cancer and our understanding of ... more 532 Background: Early mortality is a major problem in colorectal cancer and our understanding of risk factors and predictors is incomplete. A venous thromboembolism (VTE) Risk Score, comprising primary site, baseline hemoglobin, leukocyte and platelet counts, and body mass index [Khorana et al, Blood, 2008], has been shown to be associated with early mortality in solid tumors [Kuderer et al, 2008; Ay et al, 2013]. We evaluated the value of this Risk Score and other key prognostic variables in predicting early mortality for colorectal cancer (CRC) patients. Methods: CANTARISK was a prospective, non-interventional, global cohort study in patients with CRC and lung cancer initiating a new chemotherapy regimen. Clinical data were collected at 0, 2, 4, and 6 months. All data were compiled centrally and analyzed after the study closed. Risk score categories were as defined previously [Blood, 2008]. Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted odds ratios (OR) are presented. Results: A total of 1,789 CRC patients were enrolled from 2011-12; data on 1,533 evaluable patients are presented. Median age was 62 years; 71% were Caucasian. Geographic distribution was Europe 37%, North America 28%; Asia 23%; South America 12%. One-third (33%) had a rectal primary and 65% had metastatic disease. There were 184 deaths (10.3%) on study. For low, intermediate and high Risk Score, there were 8.1%, 11.2%, and 32.5% deaths, respectively. In multivariate analyses, the Risk Score remained an independent predictor of death (OR for high/intermediate vs. low score = 1.70, p = 0.0027), in addition to age (OR for each incremental year = 1.03, p = 0.0014), presence of metastatic disease (OR = 3.28, p < 0.0001), and ECOG performance status ≥2 (OR = 3.85, p < 0.0001). VTE itself was not associated with death. Conclusions: This prospective global cohort study demonstrates that the Risk Score is prognostic of early mortality in CRC patients, in addition to age, stage, and performance status. Intermediate or high-risk patients, as defined by the Risk Score, may benefit from additional interventions aimed at reducing early mortality.
During a 6-year period (1977 to 1982) blood samples from 152 Canadian patients were referred to t... more During a 6-year period (1977 to 1982) blood samples from 152 Canadian patients were referred to the national reference laboratory of the Canadian Red Cross Society because the referring hospitals had not been able to determine the cause of the patients' severe nonhemolytic transfusion reactions. Twenty-one patients were found to be IgA deficient, and 12 of them had strong class-specific anti-IgA antibodies, which were presumed to have been responsible for the reactions. The spectrum of symptoms that accompanied these violent reactions was documented for 10 of the patients. As a probable minimum, the incidence of anti-IgA-mediated reactions averaged 1.3 per million units of blood or blood products transfused during this period.
BACKGROUND: Patients with lung cancer are known to be at increased risk for venous thromboembolis... more BACKGROUND: Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). However, there have been few studies of risk factors for VTE in lung cancer patients undergoing systemic chemotherapy. METHODS: CANTARISK was a prospective, non-interventional, global cohort study including patients with lung cancer initiating a new chemotherapy regimen. Clinical data were collected at baseline and at 2, 4 and 6 months follow-up. The impact of patient-, disease- and treatment-related factors on the occurrence of VTE in the first 6 months was evaluated in univariable and multivariable Cox regression analyses. RESULTS: A total of 1,980 patients with lung cancer were enrolled from 2011-12 of which 84% were diagnosed with non-small cell lung cancer (NSCLC). Median age was 63 years (range, 25-91) and 63% were male while 82% were active or former smokers. Race was white (70%), Asian (22%), or black (4%) with similar numbers from North America, Europe, and other regions including Asia. Metastatic disease was reported in 70% and ECOG PS was ≥2 in 13%. During the first six months, 121 patients developed a VTE (6.1%), of which 47.1% had pulmonary embolism (PE), 45.5% deep venous thrombosis (DVT), 3.3% catheter-associated thrombosis, and 4.1% visceral thrombosis. Among significant factors in univariable analysis, independent predictors for VTE in multivariable Cox regression analysis included female gender, US geographic region, leg immobilization, and presence of a central venous catheter (Table) with a trend toward greater risk for higher grade histology. Although predictive of early all-cause mortality in this study population (Kuderer et al ASCO 2016), the previously validated risk score for VTE in ambulatory cancer patients (Khorana et al: Blood 2008) was not significantly associated with VTE in either univariable or multivariable analysis. CONCLUSIONS: Several demographic, geographic, and clinical factors are significantly associated with an increased risk of VTE in patients with lung cancer receiving systemic chemotherapy. Future analysis will attempt to assess how novel targeted treatment options might impact the Khorana score's predictive ability across all lung cancer patients. Disclosures Kuderer: Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Lyman:Amgen: Research Funding. Khorana:Bayer: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Halozyme: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.
BACKGROUND Venous thromboembolism (VTE) is an important complication among patients with colorect... more BACKGROUND Venous thromboembolism (VTE) is an important complication among patients with colorectal cancer but its prevalence and predictors are incompletely understood. The Khorana Score (KS), comprising primary site, baseline hemoglobin, leukocyte and platelet counts, and body mass index [Khorana et al, Blood, 2008], has been demonstrated to predict VTE in various cancer settings. We evaluated the value of this Score and other key prognostic variables in a global prospective cohort study to define the incidence, predictors and consequences of VTE in patients undergoing adjuvant or palliative chemotherapy for colorectal cancer. METHODS CANTARISK was a prospective, non-interventional, international cohort study in patients with lung and colorectal cancer on chemotherapy; data for the colorectal cohort are presented here. Clinical data were collected at baseline, and at 2, 4 and 6 months. All data were compiled centrally and analyzed after the study had closed. KS categories were as defined previously [Blood, 2008]. Statistically significant univariable associations and a priori variables were tested in multivariable models; adjusted odds ratios (OR) with confidence intervals (CIs) are presented. RESULTS A total of 1,789 patients with colorectal cancer were enrolled from 2011 to 2012. Median age was 62 years; 61% were male; 71% were Caucasian; 18% were Asian; 37% were from Europe, 28% from North America, 23% from Asia, and 12% from South America. During the six-month follow-up period, 92 (5.1%) patients experienced VTE events; 18 patients experienced 2 events each, and 2 patients experienced 3 events each, for a total of 112 VTE events. Of these 112 events, 69 (61.6%) were deep venous thromboses (DVT), 22 (19.6%) were pulmonary emboli (PE), 14 (12.5%) were catheter-associated thrombi, and 7 (6.3%) were visceral thrombi. The majority (n=94, 83.9%) were symptomatic. For low, intermediate, and high KS, there were 4.3% (n=42), 6.8% (n=39), and 12.5% (n=5) VTE events, respectively (N=1596 due to some missing values for KS components). In adjusted multivariable analyses, KS (OR for high/intermediate vs. low = 1.82, 95% CI = 1.15-2.87), ECOG performance score (OR for 2/3/4 vs. 0/1 = 2.17, 95% CI=1.07-4.43), and central venous catheter (OR for yes vs. no = 4.01, 95% CI=2.32-6.94) were independent predictors of VTE. Notably, age, metastatic (vs. non-metastatic) disease, surgery or immobilization within the prior 6 months, current smoking, and history of VTE were not associated with new VTE events. CONCLUSIONS This global prospective study demonstrates that VTE events are prevalent among patients with colorectal cancer receiving systemic chemotherapy. Khorana Score category is a strong predictor of risk. Ongoing clinical trials are focusing on the benefit of prophylactic anticoagulation in high-risk patients in these settings. Disclosures Kuderer: Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Lyman:Amgen: Research Funding. Khorana:Amgen: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.
9078Background: There are few studies of factors associated with early mortality in patients with... more 9078Background: There are few studies of factors associated with early mortality in patients with lung cancer in a real world setting. Preliminary studies of a risk score for venous thromboembolism...
558 Background: Bleeding is an important complication among patients with colorectal cancer but i... more 558 Background: Bleeding is an important complication among patients with colorectal cancer but its prevalence and predictors are incompletely understood. We evaluated data from a global prospective cohort study to define the incidence, predictors and consequences of bleeding in patients undergoing adjuvant or palliative treatment for colorectal cancer. Methods: CANTARISK was a prospective, non-interventional, international cohort study in patients with lung and colorectal cancer on chemotherapy, the patients were not on long term anticoagulation. Clinical data were collected at baseline, and at 2, 4, and 6 months. All data were compiled centrally and analyzed after the study had closed. Statistically significant univariable associations and a priori variables were tested in multivariable models; adjusted odds ratios (OR) with confidence intervals (CIs) are presented. Results: A total of 1,789 patients with colorectal cancer were enrolled from 2011-12. Median age was 62 years; 61% were male; 71% were Caucasian and 18% were Asian; 37% were from Europe, 28% from North America, 23% from Asia, and 12% from South America. Ninety-two (5.14%) patients experienced at least one bleeding episode during antineoplastic treatment, ranging from 1 to 5 episodes each, with a total of 109 episodes. The gastrointestinal tract was the source in 49 (45%) episodes. Approximately one-third of episodes (n=34, 31%) necessitated transfusion, but only 1 (0.9%) was fatal. In multivariate analysis, independent predictors of bleeding included presence of metastases (OR = 2.13, 95% CI=1.25-3.65) and surgery within prior 6 months (OR = 3.66, 95% CI=1.78-7.47) but not intact primary tumor (OR = 1.57, 95% CI=0.99-2.51). Notably, age, baseline blood counts, ECOG performance score, and anticoagulant use during study were not associated with bleeding. Conclusions: Bleeding is prevalent amongst patients with colorectal cancer receiving systemic chemotherapy. Post-surgical patients and those with metastatic disease appear to be at highest risk. Resection of the primary tumor does not appear to significantly alter risk.
Despite high initial response rates, most patients with small cell lung cancer (SCLC) relapse sho... more Despite high initial response rates, most patients with small cell lung cancer (SCLC) relapse shortly after discontinuing therapy, and cure remains an elusive goal, even for patients with limited-stage disease. For this reason, investigators have turned to the evaluation of alternative treatment strategies for patients with this malignancy. Interferon has been evaluated in four trials of adjuvant therapy after response to chemotherapy for SCLC. Different interferon preparations were used, but none of the trials showed a significant prolongation of survival. Tumor vaccines against gangliosides that are expressed on almost all human SCLC cells have been recently developed. An anti-idiotypic monoclonal antibody against the GD3 ganglioside, BEC-2, is being evaluated after chemotherapy in SCLC patients in a European study. In North America, a bivalent ganglioside vaccine, BMS-248967, is under study at the phase II level. If results are promising, a phase III trial will be undertaken. Trials of anticoagulant therapy using heparin, warfarin, and aspirin were undertaken in the 1980s and early 1990s. Although one study of warfarin and another of heparin showed trends in favor of anticoagulant therapy, there has been little research over the past decade evaluating this form of treatment of SCLC. The matrix metalloproteinase inhibitors marimastat and BMS-275291 are under evaluation in SCLC. In all trials, the matrix metalloproteinase inhibitor is administered after chemotherapy and radiotherapy as adjuvant treatment. These trials are not yet mature and survival results are not available. Miscellaneous treatments, including monoclonal antibody therapy, tamoxifen, and growth factor inhibition have not yet been shown to have a role in the treatment of SCLC. Semin Oncol 28 (suppl 4):30-37.
Background Patients with lung cancer are known to be at increased risk for venous thromboembolism... more Background Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). Venous thromboembolism is associated with increased risk for early mortality. However, there have been no studies performing a comprehensive assessment of risk factors for VTE or early mortality in lung cancer patients undergoing systemic chemotherapy in a global real-world setting. Materials and Methods CANTARISK is a prospective, global, noninterventional cohort study including patients with lung cancer initiating a new cancer therapy. Clinical data were collected until 6-month follow-up. The impact of patient-, disease-, and treatment-related factors on the occurrence of VTE and early mortality was evaluated in univariable and multivariable Cox regression analyses. A previously validated VTE risk score (VTE-RS) was also calculated (also known as Khorana score). Results Of 1,980 patients with lung cancer who were enrolled from 2011 to 2012, 84% had non-small cell lung cancer. D...
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jan 22, 2018
Anti-PD1/PD-L1 immunotherapy has demonstrated success in the treatment of advanced non-small cell... more Anti-PD1/PD-L1 immunotherapy has demonstrated success in the treatment of advanced non-small cell lung cancer (NSCLC). Recently, PD1/PD-L1 blockade also has demonstrated interesting results in small trials of neo-adjuvant treatment in Stage IB-IIIA NSCLC. In addition, several clinical trials using anti-PD1/PD-L1 as an adjuvant or neo-adjuvant treatment in resectable stage NSCLC patients are ongoing. However, few analyses of anti-PD1/PD-L1 immunotherapy related biomarkers in early stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early stage SqCLC, providing data for identifying the potential role for anti-PD1/PD-L1 treatment in early stage SqCLC patients. A total of 255 early stage SqCLC patient specimens were identified within the Strategic Partnering to Evaluate Cancer Signatures (SPECS) program participating centers. PD-L1 protein expression by I...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 13, 2017
Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed d... more Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response E...
We investigated the safety and antitumor activity of dalotuzumab, a selective anti-insulin growth... more We investigated the safety and antitumor activity of dalotuzumab, a selective anti-insulin growth factor 1 receptor monoclonal antibody (IGF1R MoAb), plus erlotinib in a sequential phase I/II trial in unselected patients with refractory advanced non-small-cell lung cancer (NSCLC).The phase I trial determined the recommended dose and safety of erlotinib plus dalotuzumab at 5 mg/kg or 10 mg/kg weekly in 20 patients. The phase II trial compared outcomes to erlotinib alone and erlotinib plus dalotuzumab at the mg/kg established in the phase I trial. Erlotinib at 150 mg plus dalotuzumab at 10 mg/kg was safe. The phase II trial included 37 patients in the erlotinib arm and 38 patients in the erlotinib plus dalotuzumab arm. Progression-free survival was 1.6 versus 2.5 months, overall survival was 10.2 and 6.6 months, and the objective response rate was 7.9% and 2.7%, respectively, with no significant differences between the two arms. Grade 3-5 adverse events occurred in 11 (28.9%) versus 1...
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