scholarly journals Absolute Eosinophil Count May be an Optimal Peripheral Blood Marker to Identify Risk of Immune-Related Adverse Events in Advanced Malignant Tumors Treated with PD-1/PD-L1 Inhibitors: A Retrospective Analysis.

2021 ◽  
Author(s):  
Yan Ma ◽  
Xiao Ma ◽  
Jingting Wang ◽  
Shanshan Shan Wu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Eosinophil Count ◽  
Malignant Tumors ◽  
Performance Status ◽  
Serum Biomarkers ◽  
Ecog Performance Status ◽  
Predictive Values ◽  
Lymphocyte Ratio ◽  
Logistic Analysis ◽  
Inhibitor Treatment

Abstract Background This study aimed to investigate the predictive values of serum biomarkers including absolute eosinophil count (AEC), neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR) with respect to immune-related adverse events (irAEs) during anti-PD-1/PD-L1 inhibitor treatment in patients with advanced malignant tumors.Methods We retrospectively analyzed 95 patients with advanced cancer who were treated with anti-PD-1/PD-L1 inhibitors from January 1, 2017 to May 1, 2020, in our cancer center. We then analyzed associations between irAEs and anti-PD-1/PD-L1 inhibitor responses and evaluated the predictive values of serum biomarkers with respect to risk of irAEs.Results The incidence of irAEs was 55.8%. There were no statistically significant differences between the irAEs and no-irAEs groups in objective response rate (ORR) or disease control rate (DCR). However, landmark analysis showed that the irAEs group had better survival after 120 days following the initiation of anti-PD-1/PD-L1 inhibitor treatment, compared with the no-irAEs group. The incidences of irAEs were greater in the high-AEC and low-NLR groups than in the low-AEC and high-NLR groups. Univariate logistic analysis showed that low NLR, ECOG performance status (0–1), and high AEC were risk factors for irAEs. Multivariate logistic analysis showed that high AEC and good ECOG performance status were independent predictors for irAEs.Conclusions irAEs may be associated with a survival benefit. Baseline AEC is a strong predictor of irAEs in patients undergoing treatment with anti-PD-1/PD-L1 inhibitors.

Update results from ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC-A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
Jin Yan ◽  
Yunwei Han ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Multicenter Phase ◽  
First Line Treatment

e15550 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial. Here we report an update on the effectiveness and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 53 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: By the data analysis cutoff date of January 22, 2021, a total of 18 patients were enrolled, of which 12 patients were available for efficacy assessment. In best overall response assessment, there were 50.0% PR (6/12), 33.3% SD (4/12) and 16.7% PD (2/12). The ORR was 50.0% (95% CI, 21.1-78.9%) and DCR was 83.3% (95% CI, 51.5-97.9%). The longest duration of treatment was 8.8 months and the response was still ongoing. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥20%) were leukopenia, hypertension, neutropenia, diarrhea, fatigue, hypertriglyceridemia. Grade 3/4 TRAEs included hypertension (22.2%), hypertriglyceridemia (11.1%), lipase elevated (11.1%) and neutropenia (5.6%). No grade 5 AEs occurred. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417.

Imfirst: A phase IIIb, safety, single arm study of carboplatin (CB) or cisplatin (CP) plus etoposide (ET) with atezolizumab (ATZ) in patients with untreated extensive-stage small cell lung cancer (ES-SCLC) in Spain—Primary safety results of the induction phase.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8567-8567
Author(s):  
Maria Rosario García Campelo ◽  
Manuel Domine ◽  
Javier De Castro ◽  
Alberto Moreno ◽  
Santiago Ponce Aix ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
Performance Status ◽  
Maintenance Phase ◽  
Tumor Biomarker ◽  
Induction Phase ◽  
Ecog Performance Status ◽  
Serious Adverse Events ◽  
Biomarker Analysis ◽  
Significant Clinical Improvement

8567 Background: Clinical trial (CT) IMpower133 met both primary endpoints and is the first CT to show significant clinical improvement over standard chemotherapy (C) with a good safety profile in first line (1L) ES-SCLC. The addition of ATZ to CB + ET resulted in an OS landmark of 34% and 22% compared to 21% and 16.8% of patients alive at 18 and 24 months respectively versus C. IMfirst evaluates ATZ + CB or CP + ET in a broader patient population than the pivotal study. ECOG Performance status (PS) 2, asymptomatic untreated brain metastases, underlying stable autoimmune diseases and HIV+ pts are eligible. IMfirst also includes the possibility of 6 C induction cycles according to investigator´s choice and consolidation radiotherapy. Methods: To evaluate the safety and efficacy of ATZ added to CB or CP + ET as 1L treatment in an interventional real world setting of ES-SCLC. Exploratory endpoints include tumor biomarker analysis related to ATZ. Results: As of Oct 2020, 117 pts had been enrolled, 105 treated with ATZ + CB + ET and 12 with ATZ + CP + ET. The median age was 65 years (Y) (range 35-89); 84 males; 14 pts (12%) had CNS metastases and 66 pts were current smokers and 50 former smokers, one had never smoked. The PS was 0 in 28 pts (24%), 1 in 75 (64%) and 2 in 14 (12%). The median of cycles of ATZ received was 4 for all the pts (range 1-12) and 2 for the pts (40) in maintenance phase (range 1-8). Number of pts with adverse events (AEs) was 109, 36 with Serious Adverse Events (SAEs) and 63 with AEs. 8 pts had SAEs related to treatment, 4 had adverse events of special interest and 13 pts discontinued the treatment due to AEs: 6 to ATZ, 12 to CB or CP and 10 to ET, 1 patient discontinued ATZ due to a related AE. Table shows the treatment related AEs (TRAEs). No grade 5 TRAEs were reported. Conclusions: IMfirst induction phase analysis confirms the safety profile of ATZ plus C in a broader population of patients. Efficacy, biomarker and further safety analyses will be presented in the future with longer follow up.[Table: see text]

A randomized, double-blind phase II study of the oral tyrosine kinase inhibitor (TKI) axitinib (AG-013736) in combination with docetaxel (DOC) compared to DOC plus placebo (PL) in metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1003-1003 ◽  
Author(s):  
H. S. Rugo ◽  
A. Stopeck ◽  
A. A. Joy ◽  
S. Chan ◽  
S. Verma ◽  
...  
Keyword(s):  
Adverse Events ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Hazard Ratio ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Grade 3

1003 Background: Single-agent DOC is commonly used to treat MBC. Axitinib (AG) is a potent TKI of VEGFRs. A phase I lead-in study identified 80 mg/m2 q3wks of DOC in combination with 5 mg BID of AG as the recommended phase 2 dose. The primary objective was to determine whether the time to progression (TTP) of AG+DOC arm is superior to DOC+PL. Methods: Pts with no prior chemotherapy for MBC and =12 mos from adjuvant chemotherapy (aCT), measurable disease, ECOG performance status (PS) of 0–2, and no uncontrolled brain metastases were randomly assigned (2:1) to receive treatment with either DOC+AG or DOC+PL without prophylactic growth factor in cycle 1. Tumor measurements were performed q9wks. Pts were stratified according to estrogen receptor (ER) status, prior aCT and PS (0–1 or 2). Results: A total of 168 pts were randomized. 92 pts had received prior aCT, 27 of whom received a prior taxane. Treatment arms were well balanced for prior adjuvant and taxane therapy. A median of 7 cycles of AG+DOC (range: 1–18) and 7 cycles of DOC+PL (range: 1–23) were administered. The most common non-hematologic adverse events observed in the AG+DOC arm included diarrhea (60%), nausea (53%), alopecia (51%), fatigue (49%), stomatitis (44%) and vomiting (40%). Grade 3/4 adverse events that were increased with AG+DOC vs DOC included febrile neutropenia (16 vs 7%), fatigue (13 vs 5%), stomatitis (13 vs 2%), diarrhea (11 vs 0%) and hypertension (5 vs 2%). Other grade 3/4 hematologic toxicities were similar in both arms. The median TTP (by RECIST) was 8.2 mo with AG+DOC arm and 7 mo with DOC+PL arm with a hazard ratio of 0.73 (prespecified, one-sided p=0.052). The overall response rate (ORR) was 40% for AG+DOC arm and 23% for DOC+PL arm (p=0.038). In a hypothesis-generating subgroup analysis, the median TTP in patients receiving prior aCT was 9.0 mo with AG+DOC arm and 6.3 mo with DOC+PL arm with a hazard ratio of 0.54 (p=0.012). Within this stratum, ORR was 45% for AG+DOC arm and 13% for DOC+PL arm (p=0.003). Conclusions: The anti-angiogenic TKI AG combined with DOC (80 mg/m2 q3wks) as first line therapy for MBC has an acceptable safety profile and promising anti-tumor activity. No significant financial relationships to disclose.

FDA analysis of ECOG performance status and safety outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12024-12024 ◽  
Author(s):  
Harpreet Singh ◽  
Yutao Gong ◽  
Pourab Roy ◽  
Bellinda King-Kallimanis ◽  
Vishal Bhatnagar ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Cumulative Incidence ◽  
Performance Status ◽  
Poor Performance ◽  
Treatment Discontinuation ◽  
Dropout Rates ◽  
Poor Performance Status ◽  
Ecog Performance Status ◽  
Eligibility Criteria

12024 Background: Patients with poor performance status are often excluded from clinical trials. The FDA has published several guidances on modernizing oncology clinical trial eligibility criteria to more accurately reflect the patient population. Many patients receiving novel oncology therapeutics are heavily pretreated, and often have comorbidities, organ dysfunction, and frailty syndromes. Little is known about the safety of novel therapeutics in patients with poor performance status. Methods: Data from six randomized trials (n=4465) leading to registration for several solid tumor and malignant hematologic cancers, including multiple therapeutic mechanisms of action, such as EGFR TKI’s, immune checkpoint inhibitors (ICI), and chemotherapy, were pooled. Cumulative incidence of Grade 3-5 adverse events and serious adverse events at Days 30, 90, and 180 were evaluated based on ECOG 0-2. Rates of treatment discontinuation by ECOG was also examined. Results: Cumulative incidence of toxicity events at days 30, 90, and 180 are shown in Table. Patient dropout rates due to death were 3.9%, 6.7%, and 10.9%; dropout rates due to disease progression were 66.5%, 66.6% and 56.9%; and dropout rates due to reasons other than progression or death were 29.7%, 26.7% and 32.1% for ECOG PS 0, 1 and 2, respectively. Conclusions: This FDA exploratory analysis of safety outcomes in registration trials based on ECOG suggests increasing rates of adverse events and rates of treatment discontinuation due to death with worsening performance status. Discontinuation rates due to disease progression and other reasons did not appear to be worse for ECOG 2 compared to 0-1. These findings were consistent across therapies (targeted therapy, ICI, chemotherapy). All trials in the analysis led to FDA approval, thus inclusion of patients with ECOG 2 did not adversely affect the trial outcome for this set of FDA approved agents. ECOG performance status eligibility criteria should be evaluated and modified on a frequent basis during drug development. Additional analysis of trials which enroll patients with ECOG 2 is needed. [Table: see text]

Comparative trial of BBR 2778 (pixantrone) + rituximab vs single agent rituximab in the treatment of relapsed/refractory indolent non-Hodgkin’s lymphoma (NHL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7578-7578 ◽  
Author(s):  
A. Santoro ◽  
J. Voglova ◽  
N. Gabrail ◽  
T. Ciuleanu ◽  
M. Liberati ◽  
...  
Keyword(s):  
Adverse Events ◽  
Response Rate ◽  
International Workshop ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Time To Progression ◽  
Open Label ◽  
Ecog Performance Status ◽  
Serious Adverse Events

7578 Background: BBR 2778 is a novel aza-anthracenedione that shows structural similarities to the anthracyclines, demonstrates single agent activity in patients with NHL, and does not exhibit cardiotoxic effects in animal models. This phase III open-label study was designed to compare the efficacy and tolerability of combination rituximab and BBR 2778, with that of single agent rituximab, in patients (pts) with relapsed or refractory indolent NHL. Methods: Pts were randomly assigned to receive both rituximab and BBR 2778 (experimental arm), or rituximab alone (control arm). In the experimental arm, pts received 375 mg/m2 rituximab IV on days 1 and 8 of cycles 1 and 2 only, and 90 mg/m2 BBR 2778 IV on days 2 and 8 of cycle 1, and on days 1 and 8 of all subsequent cycles. Pts could receive six 21-day cycles of BBR 2778. In the control arm, pts received 375 mg/m2 rituximab IV on days 1, 8 and 15 of cycle 1 and day 1 of cycle 2 only. Disease response was assessed every other cycle according to International Workshop to Standardize Response Criteria for NHL. Toxicities were assessed throughout the study using NCI-CTC criteria. Study was closed early due to poor enrollment. Results: 38 pts (20 experimental, 18 control) were enrolled. Mean age was 66 and 59 years in the experimental and control arm, respectively. Most patients were males and most had ECOG performance status 0 or 1. Efficacy is summarized in the table. Response rate (75 vs 33%) and time to progression (13.2 vs 8.1 months) were better in the BBR 2778 arm. Only pts in the experimental arm had study drug related serious adverse events (2 febrile neutropenia, 1 pneumonia, 1 neutropenia) and adverse events resulting in withdrawal (6 vs 0). Conclusions: Combination of BBR 2778 and rituximab is superior to rituximab alone with regard to time to progression and overall response rate. BBR 2778 combined with rituximab appeared to be a generally well tolerated regimen in patients with relapsed/refractory indolent NHL. [Table: see text] [Table: see text]

Phase II LAPACT trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 204-204 ◽  
Author(s):  
Pascal Hammel ◽  
Jill Lacy ◽  
Fabienne Portales ◽  
Alberto F. Sobrero ◽  
Roberto A. Pazo Cid ◽  
...  
Keyword(s):  
Adverse Events ◽  
Progressive Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Induction Phase ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Ic Treatment

204 Background: In the phase 3 MPACT study, treatment with nab-P + G resulted in a > 3-fold reduction in primary pancreatic tumor burden vs G in patients with metastatic PC, suggesting the potential for activity against LAPC. This international, multicenter single arm, phase 2 trial (LAPACT) was designed to evaluate the efficacy and safety of an induction phase regimen of nab-P + G in previously untreated patients with LAPC. Methods: Treatment-naive patients with unresectable LAPC and Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 were enrolled. The induction phase was designed as 6 cycles of nab-P 125 mg/m2 + G 1000 mg/m2 on D 1, 8, and 15 of each 28-day cycle. After induction, patients without progressive disease or unacceptable adverse events were eligible for continued treatment with nab-P + G, chemoradiation, or surgery per investigator’s choice (IC). Surgery could occur prior to completing 6 induction cycles if the investigator deemed there had been a sufficient tumor response. The primary endpoint was time to treatment failure (TTF) in patients treated with nab-P + G as induction therapy followed by IC treatment. Key secondary endpoints included disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Of 107 patients enrolled, 106 were evaluable for the safety analysis. No new toxicities were identified. The most common grade ≥ 3 treatment-emergent adverse events during induction were neutropenia (42%), anemia (11%), and fatigue (10%); grade 3 peripheral neuropathy occurred in 4% of patients. The most frequent reasons for discontinuing induction were adverse events (18%) and progressive disease (7%). Forty-six (43%) patients received IC treatment after induction: 13 (12%) continued nab-P + G, 17 (16%) received chemoradiation, and 16 (15%) underwent surgical resection (R0, n = 7; R1, n = 9). DCR and ORR during induction were 78% and 35%, respectively; with a median TTF of 8.6 months and median PFS of 10.2 months. Conclusion: A nab-P + G induction regimen in LAPC appears tolerable and feasible and is associated with encouraging antitumor activity and promising TTF and PFS. NCT02301143. Clinical trial information: NCT02301143.

scholarly journals High Risk Older AML Patients May be Benefited from the Treatment of Decitabine Combined Wih CAG Regimens

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4953-4953
Author(s):  
Xia Xiao ◽  
Mingfeng Zhao ◽  
Qi Deng ◽  
Qing Li ◽  
Juan Mu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Adverse Events ◽  
Older Patients ◽  
Median Overall Survival ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Ecog Performance Status ◽  
Secondary Aml ◽  
Number Of Patients

Abstract Patients over age 60 maked up more than 50% of newly diagnosed patients with acute myeloid leukemia (AML). Futhermore, with an aging population, more and more older AML patients were diagnosed in China. But the treatment approaches of this disease were variable, with many uncertainties and controversies. Treatment options for older patients with adverse prognostic features, such as poor performance status, unfavorable cytogenetics or an antecedent hematologic disorder were limited, and outcomes were poor. Aggres­sive induction chemotherapy had a high mortality and relatively low efficacy in this population. There were several new therapeutic schemes for older patients with AML. CAG regimens consisting of low-dose cytarabine, aclarubicin and granulocyte-colony stimulating factor for the treatment of older patients with AML showed higher rates of CR (42-68%). Decitabine, a DNA-hypomethylating agent induces differentiation and apoptosis of leukemic cells. The current National Comprehensive Cancer Care guidelines suggested decitabine as alterative options for older patients with AML. Previous studies have shown that decitabine demonstrated efficacy in a phase II multicenter study of older patients with AML, with a CR rate of 25%, 30-day mortality of 7%, median overall survival 7.7 months and little extramedullary toxicity. In our study, decitabine(15 mg/m2/d, d1-5) combined with CAG regimens (aclarubicin 20 mg/d, d3-6, Ara-C 10 mg/m2, q12h, d3-9, G-CSF 300ug, qd, d1-9) treated 27 older patients with AML, repeated every 4 weeks. Effectiveness and safety were assessed. 27 older patients with newly diagnosed AML who were in Tianjin First Central Hospital of China from January 2011 to December 2013 were enrolled in our study. They were all treated with decitabine combined with CAG regimens. The characteristics of the 27 patients were described in Table I. The study population included 15 males and 12 females, with a median age of 68 years (range 60-79 years). All patients had Eastern Cooperative Oncology Group (ECOG) performance status of <3. Cytogenetics were classified according to criteria of the Cancer and Leukemia Group B(CALGB), and were adverse in 11 patients (40.7%) and intermediate in 16 patients (59.3%). No patient had favorable cytogenetics. 12 patients (44.4%) had secondary AML or an antecedent MDS or myeloproliferative disorder. Molecular diagnostics with mutations of FLT3-ITD in 6 patients (22.2%), NPM1 in 7 patients (25.9%) patients and JAK-2 in 4 patients (14.8%). Clinical responses, survival and adverse events of all 27 patients were analyzed. The median treatment cycle was 4 cycles. Rate of complete remission, overall response rate and a 30-day mortality rate were 40.1%, 66.7%, 7.4%, respectively. The median overall survival and median recurrence-free survival were 13.0months (95%CI, 7.0-18.0 months ) and 7.0 months (95%CI, 3.0-11.0 months), respectively. Adverse events in the regimens were mainly included myelosuppression, infection, nausea, vomiting and liver dysfunction. The adverse events could be well tolerated after managements. In conclusion, the treatment of decitabine combined with CAG regimens was found to be feasible and useful in high-risk older patients with AML. This regimen was a well-tolerated therapeutic alternative, was effective in producing remissions lasting several months or disease stabilization in high-risk older patients with AML. Table 1. The characteristics of newly diagnosed patients with AML Total number of patients n=27 median age(range) 68 years(60-79 years) Male/female 15/12 (1.25/1) ECOG performance status, n (%) 0 5 (18.5%) 1 10 (37.0%) 2 12 (44.4%) Cytogenetics, n (%) Adverse 11 (40.7%) Intermediate 16 (59.3%) secondary AML, n (%) MDS 6 (22.2%) myeloproliferative 5 (18.5%) Other tumors 1 (3.7%) Molecular mutations, n (%) FLT3-ITD 6 (22.2%) NPM1 7 (25.9%) JAK-2 4 (14.8%) Disclosures No relevant conflicts of interest to declare.

scholarly journals Association of Blood Biomarkers and Autoimmunity with Immune Related Adverse Events in Patients with Cancer treated with Immune Checkpoint Inhibitors

2021 ◽  
Author(s):  
Despina Michailidou ◽  
Ali Khaki ◽  
Maria Morelli ◽  
Leonidas Diamantopoulos ◽  
Namrata Singh ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Cancer Type ◽  
Blood Biomarkers ◽  
Lymphocyte Ratio ◽  
Patients With Cancer ◽  
History Of

Abstract Background: Patients with cancer treated with immune checkpoint inhibitors (ICIs) develop immune related adverse events (irAEs), however biomarkers are lacking. We hypothesized that clinicopathologic and laboratory factors would be associated with irAE risk and overall survival (OS) in this population.Methods: In a retrospective study of patients treated with ICIs we collected clinicopathologic, laboratory, irAEs and outcomes data. The association between baseline blood biomarkers, clinicopathologic features and irAEs was assessed by logistic regression adjusting for age, sex, smoking, cancer type, performance status, concomitant other systemic therapy, history of autoimmune disease (AD) and chronic infection. Optimal cutoff values of biomarkers were identified by recursive partitioning analysis.Results: 470 patients were identified; 156 (33%) developed irAEs, which were associated with baseline absolute lymphocyte count >2.6k/ul (adjusted [a]OR:4.12), neutrophil to lymphocyte ratio (NLR) ≤5.3 (aOR:2.08) and monocyte to lymphocyte ratio (MLR)≤0.73 (aOR:3.11). Patients with pre-existing AD (aOR:2.81), family history of AD (aOR:5.86), and ICI combination (aOR:2.26) had higher odds of irAEs. Baseline NLR≤5.3 (aHR:0.68) and MLR≤0.73 (aHR:0.43) were associated with longer OS.Conclusion: irAE were associated with autoimmune history, ICI combination and baseline laboratory measurements. Lower NLR and MLR may have favorable prognostic value. Our hypothesis-generating findings require validation in larger prospective studies.

Outcomes and safety analysis of a phase IB trial of stereotactic body radiotherapy (SBRT) to all sites of oligometastatic non-small cell lung cancer combined with durvalumab and tremelimumab.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21212-e21212
Author(s):  
Michael Frederick Bassetti ◽  
Nan Sethakorn ◽  
Joshua Michael Lang ◽  
Jennifer L. Schehr ◽  
Zachery Schultz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Performance Status ◽  
Cohort Analysis ◽  
Median Number ◽  
Ecog Performance Status ◽  
Phase Ib ◽  
Grade 3 ◽  
Metastatic Sites

e21212 Background: Combining local ablative and systemic therapies in patients with oligometastatic NSCLC leads to improved overall survival (OS) and progression-free survival (PFS). The potential immunostimulatory effects of ablating all visible disease with SBRT in combination with dual immune checkpoint inhibition has prompted interest, but the toxicity and benefit are unknown. Methods: We conducted a phase Ib study to investigate the safety of SBRT, with doses between 30 and 50 Gy in five fractions to all sites of disease, followed by durvalumab 1500 mg IV in combination with tremelimumab 75 mg IV every 4 weeks x 4 cycles, followed by durvalumab maintenance until progression. Eligible patients had 1-6 extracranial metastatic sites, allowing multiple metastases per location, with all lesions suitable for SBRT, ECOG performance status 0-1, no actionable driver mutation, and no prior immunotherapy. The primary endpoint was safety of this combination. Secondary endpoints include PFS and OS. Dose-limiting toxicities (DLTs) (any Grade ≥ 3 toxicity) were evaluated from the first administration of SBRT until 28 days post start of durvalumab and tremelimumab. Baseline tumor mutational burden, PD-L1 expression on post-SBRT biopsy and circulating tumor cells will be correlated with outcomes. In this first cohort analysis, we assess the safety and outcomes of the first 17 patients. Results: From 2/2018-2/2021, the first 17 pts were enrolled. Characteristics of those enrolled included: median age 68 years, female/male 4/13, squamous/non-squamous 2/15, median number of non-central nervous system (CNS) metastatic sites 2 (1-5), median number of non-CNS metastatic lesions 2 (1-9), CNS involvement 6/17 (35.3%), previous treatment 4/17 (23.5%). DLTs were seen in 2/17 (11.8%) patients; DLTs were autoimmune hepatitis and autoimmune pancreatitis. Most treatment-related adverse events (TRAEs) were grade (G) 1/2. TRAEs included: all TRAEs n = 188, 88.2% (of patients); G 3 n = 17, 29.4%; G 4 n = 1, 5.8%. There were no treatment-related deaths. Five patients discontinued treatment due to grade 3/4 immune related adverse events (IRAE). At a median follow up of 20 months 11/17 (64.7%) patients are alive with 10/17 (58.8%) with no evidence of disease (NED). Six of 17 (35.2%) patients experienced disease progression and 4/17 (23.5%) patients died of disease progression. Median PFS and OS are not yet reached. Conclusions: There were no unexpected safety signals in the cohort of patients enrolled. The incidence of grade ≥ 3 IRAEs is similar to the treatment of advanced NSCLC and no additional toxicity was observed with the addition of SBRT. Clinical outcomes look promising with median OS and PFS not yet reached at 20 months median follow up. The study continues to enroll a second cohort and results will be updated. Clinical trial information: NCT03275597.

Treatment with bevacizumab in patients with metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14083-e14083
Author(s):  
Janja Ocvirk ◽  
Martina Rebersek ◽  
Marko Boc ◽  
Maja Ebert Motara ◽  
Tanja Mesti
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Metastatic Disease ◽  
Performance Status ◽  
Progression Free Survival ◽  
Routine Clinical Practice ◽  
First Line ◽  
Ecog Performance Status ◽  
Good Tolerability ◽  
Previously Treated

e14083 Background: This study was designed to prospectively evaluate the safety and toxicity of bevacizumab in mCRC patients (pts) with mCRC pts in routine clinical practice as well as selection of pts. Methods: Baseline characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected from 273 mCRC pts who started bevacizumab-containing therapy between January 2008 and August 2010. Results: The data from 273 pts (median age 62) were included in the evaluation. The ECOG performance status (PS) at baseline was 0 in 60%, 1 in 37% and 2 in 3% of pts. Eighty pts (29%) received adjuvant chemotherapy, and 84 (31%) received chemotherapy ± bevacizumab or cetuximab for prior treatment of metastatic disease. Majority of the 273 pts received irinotecan-based chemotherapy (65%). Complete response (CR) was reported in 7%, partial response (PR) in 31% and stable disease (SD) in 36% of the first-line treated pts. In pts previously treated for metastatic disease CR, PR and SD were 6%, 24% and 45%, respectively. In the first-line pts median progression-free survival (PFS) was 10.9 months (95% confidence interval [CI], 9.8 - 12.0), while median overall survival (OS) was 24.3 months (95% CI, 21.4 – 30.3). PFS was 10, 9 and 8.7 months and OS was 16.7, 13.5 and 12.8 months in pts previously treated for metastatic disease with chemotherapy, chemotherapy + cetuximab or chemotherapy + bevacizumab, respectively. Two-year survival rate was 51% in the first-line pts and 32%, 14% and 38% in pts previously treated for metastatic disease with chemotherapy, chemotherapy + cetuximab and chemotherapy + bevacizumab, respectively. Metastasectomy was performed in 39 (15.5%) of the pts. One hundred and nine pts received bevacizumab with subsequent chemotherapy and CR, PR and SD were 1%, 9% and 30%. Overall rates of bevacizumab-related grade 1-2/3-4 adverse events were: proteinuria 38/9 %, hypertension 16/3 %, thromboembolic events 1/5 %, infection 2/3 %, bleeding 2/1 % and fistula 0/1 %. Conclusions: The authors concluded that bevacizumab-containing therapy and use of bevacizumab for long period of time demonstrated efficacy and good tolerability when used as a first-, second- and third-line treatment in routine clinical practice.

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