Determinants of early discontinuation of first-line chemotherapy, and associated outcomes among elderly with advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9102-9102
Author(s):  
Pramit Nadpara
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Performance Score ◽  
First Line ◽  
Early Discontinuation ◽  
Primary Treatment Modality ◽  
Comorbidity Burden ◽  
Patient Reported ◽  
The Impact ◽  
Line Chemotherapy

9102 Background: Chemotherapy is the primary treatment modality in elderly with Advanced-NSCLC (Adv-NSCLC), with ASCO/NCCN guideline recommending First-Line Chemotherapy (FL-Chemo) for at least 4 months. The objective of this study was to identify the determinants, and outcomes of early discontinuation of FL-Chemo, in a nationwide sample of elderly patients. Methods: We used NCI’s Surveillance, Epidemiology, and End Results registry linked Medicare (SEER-Medicare) 2007-2014 files. We included patients with NSCLC diagnosis in 2007-2013, age ≥65, AJCC Stage IIIB/IV, receiving only FL-Chemo (Identified using HCPCS/CPT codes), and surviving at least 9 months post-diagnosis. We excluded those with non-continuous Medicare enrollment, or HMO enrollment. Patients receiving 1-3 months (vs. 4-7 months) of FL-Chemo were characterized as those experiencing early discontinuation. Patient’s performance status and comorbidity burden were assessed using previously validated algorithms. Survival was calculated from the diagnosis date to the date of death/study end date. Chi-square test, logistic regression, survivor function, proportional hazards regression, and propensity score–adjusted modeling were conducted. Results: We identified 1,029 patients (meeting inclusion and exclusion criteria) with incident Adv-NSCLC during the study years. Of those, 43.2% patients experienced early discontinuation. Adjusted analysis revealed Age as the only significant factor associated with early FL-Chemo discontinuation, with odds increasing with increase in age (p < 0.035). Other patient factors (non-clinical and clinical factors including performance score, comorbidity) were not associated with early discontinuation in any model. Survival outcomes and mortality risk were poor among those experiencing early discontinuation, however the difference was not statistically significant (p < 0.165). Conclusions: A large proportion of elderly with Adv-NSCLC experience early discontinuation of FL-Chemo. Even after controlling for variability in patient performance score and comorbidity burden, Age remained a key factor associated with early discontinuation, raising a cause for concern. Future studies need to explore the impact of Age along with patient reported Quality of Life on early treatment discontinuation.

Analysis of chemotherapy efficacy according to histology in malignant pleural mesothelioma (MPM) patients (p).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20563-e20563
Author(s):  
Susana Cedres Perez ◽  
Juan David Assaf Pastrana ◽  
Patricia Iranzo ◽  
Ana Callejo ◽  
Nuria Pardo ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Survival Data ◽  
Cox Regression ◽  
Asbestos Exposure ◽  
Performance Status ◽  
University Hospital ◽  
First Line ◽  
Neutrophil Lymphocyte Ratio ◽  
The Impact ◽  
Line Chemotherapy

e20563 Background: MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. Histology is a prognostic factor and recently CheckMate 743 trial demonstrated survival benefit of immunotherapy in first line with some differences in the efficacy of chemotherapy according to histology. However, randomized trials who led to the approval of antifolate in mesothelioma did not include analysis of outcomes by histology. The objective of this study is to characterize the impact of chemotherapy according to histology in p with MPM at our institution. Methods: We review 189 MPM p diagnosed at Vall d´Hebron University Hospital between November 2002 and April 2020. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: Patient’s characteristics: median age 68 years (y) (45-88 y), males: 70%, performance status (PS)1: 69%, asbestos exposure: 75%, epithelioid subtype: 76%. First line chemotherapy was offered to 85% of p (66% cisplatin-pemetrexed and 27% carboplatin-pemetrexed). Median overall survival (OS) in overall population was 21.3 m (95%CI17.2-24.3). Epithelioid histology, PS 0, neutrophil-lymphocyte ratio <5 and treatment with cisplatin vs carboplatin were associated with significant improvements in OS (p<0.001). When we analyzed the survival of patients who received first line chemotherapy according to histology, we found that patients with epithelioid tumors had better PFS and OS. Median PFS for p with epithelioid tumors treated with chemotherapy in first line was 4.8 m versus 3.6 months non-epithelioid (HR1.5 CI95% 1.1-2.3; p=0.03). OS of epithelioid p treated with first line chemotherapy was 26.7 m versus 15.0 m non-epithelioid patients (HR2.25 CI95% 1.4-3.4; p<0.001). We analyzed if the differences in survival according to histology were due to type of systemic treatment received (Table). Conclusions: In our series, p with non-epithelioid tumors presented worse prognosis. We confirmed histology is a prognostic factor with better OS for p with epithelioid tumors. Moreover, we demonstrated better efficacy of chemotherapy in epithelioid tumors, although histology is not a predictive factor for the platinum agent sensitivity (p of interaction PFS=0.09, p of interaction OS= 0.65).[Table: see text]

Impact of gemcitabine (G) on the activity of first-line chemotherapy in non-small cell lung cancer (NSCLC): A meta-analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7138-7138
Author(s):  
G. L. Pappagallo ◽  
O. Belvedere ◽  
O. Vinante ◽  
F. Grossi
Keyword(s):  
Meta Analysis ◽  
Performance Status ◽  
Objective Response ◽  
Response To Treatment ◽  
Third Generation ◽  
First Line ◽  
Significant Difference ◽  
Nsclc Patients ◽  
The Impact ◽  
Line Chemotherapy

7138 Background: A two-drug platinum-based regimen in which cisplatin or carboplatin is combined with a third-generation agent (i.e. paclitaxel, vinorelbine, docetaxel, or G) is the standard first-line treatment for NSCLC patients with good performance status. Encouraging results have recently been reported for nonplatinum regimens composed of two third-generation drugs. Methods: To assess the impact of G on the activity of first-line chemotherapy in NSCLC, we carried out a meta-analysis on data from 4,362 NSCLC patients who were enrolled in 11 randomized trials comparing a G-containing vs. G-free new generation regimens. We constructed 2x2 tables using response to treatment data. For trials with more than one eligible G-free comparator arm, individual comparisons between the G-based treatment arms and each of the comparator arms were analyzed. A general variance-based method was used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). We assessed for heterogeneity among the trials based on standard methods. Results: Sixteen comparisons contributed to this analysis. G-containing regimens included: G+cisplatin (894), G+docetaxel (565), G+paclitaxel (200 patients), G+vinorelbine (157), G+carboplatin (49). G-free regimens included: vinorelbine+cisplatin (866), carboplatin+paclitaxel (539), docetaxel+cisplatin (494), cisplatin+paclitaxel (439), vinorelbine+carboplatin (159). Comparing G-containing vs. G-free regimens, the OR for progression was 0.867 (CI 95% 0.770–0.977; p = 0.019), with heterogeneity chi-square 11.639 (p = 0.71). No significant difference was observed for complete (OR 0.909, CI 95% 0.556–1.487; P = 0.707) and overall (complete + partial) response (OR 0.987, CI 95% 0.881–1.106; P = 0.819). Conclusions: These data demonstrate that the progression of disease is more likely in patients treated with G-free doublets. Further analyses are required to address whether disease control (objective response + stable disease) is associated with a survival benefit and may therefore be used as a surrogate end point for survival in chemotherapy trials of NSCLC. No significant financial relationships to disclose.

Clinical outcomes of pancreas cancer patients with peritoneal spread: Results from the chord consortium.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19268-e19268
Author(s):  
Mehrnoosh Pauls ◽  
Abdulaziz AlJassim AlShareef ◽  
Winson Y. Cheung ◽  
Rachel Anne Goodwin ◽  
Brandon M. Meyers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Advanced Pancreatic Cancer ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
First Line ◽  
The Impact ◽  
Line Chemotherapy

e19268 Background: Prior studies have demonstrated that clonal cells that give rise to pancreatic peritoneal metastases (PM) are geographically and genetically distinct from clonal cells, giving rise to lung and liver metastases. The objective of this study was to assess if there is a distinct difference in prognosis and therapeutic response among patients with pancreatic cancer with (PM compared to the lung/liver. Methods: Using a retrospective cohort design, medical records from adult patients diagnosed with metastatic adenocarcinoma of the pancreas at five Canadian academic cancer centers (2014 - 2019) were reviewed. Prognostic variables including age, Charlson comorbidity index, ECOG, cigarette smoking, nodal status, sites of metastases, and first line chemotherapy were collected. Cox proportional hazards model (MVA) was used to examine the association between peritoneal involvement and survival, adjusted for measured confounders. Analyses were completed using SAS, where alpha of 0.05 was defined as the level of significance. Results: A total of 1161 patients were included. Metastatic sites included peritoneum (n = 170, 14.6%), lung (n = 145, 12.5%) and liver (n = 563, 48.5%). Patients with PM received first-line FOLFIRINOX (FFX, n = 31), Gemcitabine + nab-paclitaxel (G/N, n = 20), Gemcitabine (G, n = 18), and no treatment (n = 97). In univariate analyses, worse ECOG PS was associated with PM (p = 0.002). The majority of patients died (89%), with a median overall survival (OS) of 3 vs 7 months for patients with PM and those without PM (p < 0.001), respectively. The median OS in patient whom receive first-line chemotherapy was 7 months in FFX group (95% CI 1.66-12.33), 6 months in G/N (95% CI 4.54-7.45) and 2 months in G group (95% CI 1.42-2.57). Patients had significantly better OS when treated with FFX or G/N compared to G alone (p = 0.002). Time to treatment failure was significantly shorter among patient treated with G alone compare to patients treated with FFX and G/N (P < 0.005). Conclusions: In the setting of combination chemotherapy for advanced pancreatic cancer, patients with PM continue to have a poor prognosis. This may be due to the impact of PM on PS and the inability to administer palliative chemotherapy. For eligible patients, FFX or G/N results in a higher OS than G monotherapy.

First-line chemotherapy plus cetuximab in patients grouped according to prognostic risk factors: Analysis of the CRYSTAL and OPUS studies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3591-3591
Author(s):  
Gunnar Folprecht ◽  
Eric Van Cutsem ◽  
Carsten Bokemeyer ◽  
Michael Schlichting ◽  
Steffen Heeger ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Risk Groups ◽  
Rank Test ◽  
Clinical Parameters ◽  
First Line ◽  
Ecog Performance Status ◽  
Hazards Model ◽  
Line Chemotherapy

3591 Background: Analysis of randomized trials has shown that mCRC patients (pts) can be divided into prognostic risk groups according to baseline clinical parameters including ECOG performance status, white blood cell count (WBC), alkaline phosphatase (ALP) and number of metastatic (met) sites (Köhne C, et al. Ann Oncol 2002;13:308-17). The effect of adding cetuximab to first-line chemotherapy (CT) on overall survival (OS) in these groups of KRAS wild-type mCRC pts was investigated in the CRYSTAL and OPUS studies. Methods: Pt risk groups were: low-risk (LRG= ECOG 0/1, 1 met site) intermediate-risk (IRG= ECOG <1, >1 met site, ALP <300 U/L or, ECOG>1, low WBC, 1 met site) and high-risk (HRG= ECOG<1, >1 met site, ALP>300 U/L or ECOG>1, high WBC, or ECOG>1, low WBC and >2 met sites). Exploratory analyses comprised estimates of effects using Cox‘s proportional hazards model for OS on individual pt data and comparison of treatment arms by log-rank test. Results: Data are shown in the table. In the pooled analyses, in both treatment arms OS was longest in LRG pts and shortest in HRG pts. Adding cetuximab to CT led to marked improvements in OS in the HRG (Hazard ratio [HR] 0.765, 95% CI 0.506–1.157, p=0.203) and IRG (HR 0.781, 95% CI 0.622–0.981, p=0.033), while improvements in LRG pts (HR 0.869, 95% CI 0.672–1.124, p=0.287) were observed only after prolonged follow up. Data were similar in the separate CRYSTAL and OPUS studies. Conclusions: The analysis confirms the concept of prognostic risk groups for OS according to baseline clinical parameters in pts with KRAS wt mCRC. Benefit from the addition of cetuximab to first-line CT in terms of OS appears to be more pronounced in the IRG and HRG. [Table: see text]

Randomized multicenter trial of 3 weekly cabazitaxel versus weekly paclitaxel chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer (MBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1008-1008
Author(s):  
Amit Bahl ◽  
Jeremy Braybrooke ◽  
Alicia Bravo ◽  
Emily Foulstone ◽  
Jessica Ball ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Performance Status ◽  
Objective Response ◽  
Significant Risk ◽  
Weekly Paclitaxel ◽  
First Line ◽  
Patient Reported ◽  
Grade 3 ◽  
Line Chemotherapy

1008 Background: Paclitaxel is commonly used as first line chemotherapy for HER2 negative MBC. However, with response rates of 21.5-53.7% and a significant risk of peripheral neuropathy there is a need for more effective and better tolerated chemotherapy (CCT). Methods: This open label randomised (1:1) phase 2 trial compared 6 cycles of cabazitaxel (25 mg/m2) every 3 weeks, with weekly paclitaxel (80mg/m2) over 18 weeks as first line CCT. HER2 negative and performance status ≤1 patients were eligible. Patients on cabazitaxel received GCSF prophylaxis. Primary endpoint was Progression Free Survival (PFS) with 127 events required to detect a hazard ratio (HR) of 0.65 with 85% power. Secondary endpoints included objective response rate (ORR; RECIST 1.1), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). Results: 158 patients were recruited from 14 UK hospitals (79 in each arm). Median age (range) was 56(34-81) in the cabazitaxel arm and 61(34-79) in the paclitaxel arm. 61% of patients were performance status 0. Median time on treatment was 15 weeks for both arms, but more patients on paclitaxel had a treatment delay (61% vs 39%) or dose reduction (37% vs 24%). Comparing cabazitaxel to paclitaxel after 146 PFS events, median PFS was 6.7 vs 5.8 months (HR 0.84; 95%CI 0.60–1.18, P = 0.3). There was no difference in OS, median 19.3 vs 20.0 months (HR 0.94; 95%CI 0.63-1.40, P = 0.7), ORR (42% vs 37%) or TTR (HR 1.09; 95%CI 0.68–1.74, P = 0.7). Grade ≥3 adverse events occurred in 42% of patients on cabazitaxel and 48% on paclitaxel. Diarrhoea, febrile neutropenia and nausea were the most common grade ≥3 events in the cabazitaxel arm with rates of 11%, 11% and 10% respectively compared to 1%, 1% and 0% in the paclitaxel arm. In the paclitaxel arm the top grade ≥3 events were lung infection and peripheral neuropathy, 6% and 5% respectively compared to 2.5% and 0% in the cabazitaxel arm. Peripheral neuropathy of any grade was reported by 55% of patients treated with paclitaxel vs 17% on cabazitaxel. Alopecia occurred in 41% of patients on paclitaxel compared to 27% on cabazitaxel. Adverse events leading to discontinuation were more frequent with paclitaxel (22%) than cabazitaxel (14%). Over the course of treatment, mean EQ5D single index utility score (+0.05; 95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1-12.3, P = 0.001) were higher in the cabazitaxel arm compared to paclitaxel suggestive of better QoL on Cabazitaxel. Conclusions: 3 weekly cabazitaxel as first line chemotherapy in HER2 negative MBC does not significantly improve PFS compared to weekly paclitaxel, though it has a lower risk of peripheral neuropathy with better patient reported overall health outcomes. Cabazitaxel is safe and well tolerated for MBC and requires fewer hospital visits, an important consideration in the COVID pandemic and beyond. Clinical trial information: NCT03048942 .

Impact of KRAS mutational status on outcomes in patients with pancreatic cancer (PDAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4142-4142
Author(s):  
Lucy Xiaolu Ma ◽  
Gun Ho Jang ◽  
Amy Zhang ◽  
Robert Edward Denroche ◽  
Anna Dodd ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Advanced Disease ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
First Line ◽  
Kras Mutations ◽  
Kaplan Meier ◽  
Mutational Status ◽  
Translational Research Program ◽  
The Impact

4142 Background: KRAS mutations (m) (KRASm) are present in over 90% of pancreatic adenocarcinomas (PDAC) with a predominance of G12 substitutions. KRAS wildtype (WT) PDAC relies on alternate oncogenic drivers, and the prognostic impact of these remains unknown. We evaluated alterations in WT PDAC and explored the impact of specific KRASm and WT status on survival. Methods: WGS and RNAseq were performed on 570 patients (pts) ascertained through our translational research program from 2012-2021, of which 443 were included for overall survival (OS) analyses. This included 176 pts with resected and 267 pts with advanced PDAC enrolled on the COMPASS trial (NCT02750657). The latter cohort underwent biopsies prior to treatment with first line gemcitabine-nab-paclitaxel or mFOLFIRINOX as per physician choice. The Kaplan-Meier and Cox proportional hazards methods were used to estimate OS. Results: KRAS WT PDAC (n = 52) represented 9% of pts, and these cases trended to be younger than pts with KRASm (median age 61 vs 65 years p = 0.1). In resected cases, the most common alterations in WT PDAC (n = 23) included GNASm (n = 6) and BRAFm/fusions (n = 5). In advanced WT PDAC (n = 27), alterations in BRAF (n = 11) and ERBB2/3/4 (n = 6) were most prevalent. Oncogenic fusions (NTRK, NRG1, BRAF/RAF, ROS1, others) were identified in 9 pts. The BRAF in-frame deletion p.486_491del represented the most common single variant in WT PDAC, with organoid profiling revealing sensitivity to both 3rd generation BRAF inhibitors and MEK inhibition. In resected PDAC, multivariable analyses documented higher stage (p = 0.043), lack of adjuvant chemotherapy (p < 0.001), and the KRAS G12D variant (p = 0.004) as poor prognostic variables. In advanced disease, neither WT PDAC nor KRAS specific alleles had an impact on prognosis (median OS WT = 8.5 mths, G12D = 8.2, G12V = 10.0, G12R = 12.0, others = 9.2, p = 0.73); the basal-like RNA subtype conferred inferior OS (p < 0.001). A targeted therapeutic approach following first line chemotherapy was undertaken in 10% of pts with advanced PDAC: MMRd (n = 1), homologous recombination deficiency (HRD) (n = 19), KRASG12C (n = 1), CDK4/6 amplification (n = 3), ERBB family alterations (n = 2), BRAF variants (n = 2). OS in this group was superior (14.7 vs 8.8 mths, p = 0.04), mainly driven by HRD-PDAC where KRASm were present in 89%. Conclusions: In our dataset, KRAS G12D is associated with inferior OS in resected PDAC, however KRAS mutational status was not prognostic in advanced disease. This suggests that improved OS in the WT PDAC population can only be achieved if there is accelerated access to targeted drugs for pts.

scholarly journals Health-related quality Of Life In patients with advanced Soft TIssue sarcomas treated with Chemotherapy (The HOLISTIC study): protocol for an international observational cohort study

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e035171 ◽  
Author(s):  
Eugenie Younger ◽  
Robin L Jones ◽  
Ingrid M E Desar ◽  
Clare Peckitt ◽  
Winette T A van der Graaf ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Health Related Quality ◽  
First Line ◽  
Patient Reported ◽  
Related Quality ◽  
Health Related ◽  
Line Chemotherapy

IntroductionChemotherapy is the mainstay of treatment for patients with advanced soft tissue sarcomas (STS). Treatment intent is usually palliative, aiming to improve symptoms, stabilise or reduce tumour burden and extend life. Clinical trials have traditionally used radiological response, time to progression and survival as measures of treatment efficacy. Health-related quality of life (HRQoL) is at least equally important or more important than survival for many patients with advanced cancer. Systematically collecting HRQoL data during chemotherapy can provide greater insight into treatment efficacy from the patient perspective.The primary aims of this study are to evaluate HRQoL in patients with advanced STS treated with chemotherapy over time, explore the decision-making process and patient reflection post-treatment.Methods and analysisThis is an observational, international cohort study for 132 patients aged ≥18 years with advanced STS treated at eight centres (three in the UK, five in the Netherlands). Patients will be recruited prior to starting first-line or third-line chemotherapy and invited to complete questionnaires using the Patient-Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship registry (PROFILES); an established international registry for collection of cancer patient-reported outcomes. Online (or paper) questionnaires will be completed at baseline, each cycle of chemotherapy and 2–3 monthly during follow-up. The questionnaire package includes the Decisional Conflict Scale, Control Preferences Scale, Quality–Quantity Questionnaire, treatment expectations, European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30), EORTC financial toxicity items, Work Ability Index, Functional Assessment of Cancer Therapy-General (FACT-G) items and Decisional Regret Scale. Clinical data will be extracted from patient records and linked with questionnaire responses. The primary outcome measure is the change in global HRQoL from baseline to after cycle 4 of first-line chemotherapy (based on published data showing that patients with advanced STS complete a median number of four cycles of first-line chemotherapy).Ethics and disseminationHeath Research Authority and Research Ethics Committee (REC 17/NI/0197). Results from the Health-related quality Of Life In patients with advanced Soft TIssue sarcomas treated with Chemotherapy (HOLISTIC) study will be published in peer-reviewed journals and disseminated at local, national and international conferences. We will also present our findings at any appropriate patient meetings and involve patients in study-related publications.Trial registration numberNCT03621332.

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