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]

Analysis of mismatch repair (MMR) proteins expression in a series of malignant pleural mesothelioma (MPM) patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20062-e20062
Author(s):  
Susana Cedres ◽  
Santiago Ponce Aix ◽  
Ana Callejo ◽  
Nuria Pardo ◽  
Alejandro Navarro ◽  
...  
Keyword(s):  
Protein Expression ◽  
Survival Data ◽  
Cox Regression ◽  
Asbestos Exposure ◽  
Performance Status ◽  
Predictive Biomarkers ◽  
University Hospital ◽  
Tumor Biomarker ◽  
Neutrophil Lymphocyte Ratio ◽  
Mmr Proteins

e20062 Background: The increasing incidence and poor outcome associated with MPM demand identification of effective treatment options. Promising results have been reported with immunotherapy (IO) in a small proportion of MPM patients (p). MMR deficiency (dMMR) has been well described in several malignancies and was recently approved as a tumor biomarker for IO with anti-PD-1 checkpoint inhibitor. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM p. Methods: Tumors of 159 MPM p from Vall d´Hebron University Hospital and October 12th University Hospital diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR when any MMR protein expression was negative and MMR intact when all MMR proteins were positively expressed. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: P characteristics: median age: 69 years (29-88 years), males: 71%, performance status (PS) 1:69%, asbestos exposure: 52%, stage III at diagnosis: 42%, epithelial subtype: 65%, systemic treatment 81% (57% chemotherapy with cisplatin plus pemetrexed in first line), 50% received second line and 28% third line. MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8m). In a multivariate model factors associated to improved mOS were PS 0 vs PS2 (13 v 2 m, HR 12.8, p < 0.01), neutrophil-lymphocyte ratio (NLR) < 5 (18 v 9 m in NLR ≥5,HR 1.5, p < 0.05) and epitheliod vs sarcomatoid histology (18 vs 4 m HR 4.7, p < 0.01). Thirteen p received IO with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1m). Conclusions: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate novel predictive biomarkers benefit from IO in MPM.

scholarly journals Efficacy of Chemotherapy for Malignant Pleural Mesothelioma According to Histology

2021 ◽  
Author(s):  
Susana Cedres ◽  
Juan David Assaf ◽  
Patricia Iranzo ◽  
Ana Callejo ◽  
Nuria Pardo ◽  
...  
Keyword(s):  
Survival Data ◽  
Cox Regression ◽  
Progression Free Survival ◽  
University Hospital ◽  
First Line ◽  
Kaplan Meier ◽  
Platinum Agent ◽  
Clinical Records ◽  
The Impact ◽  
Line Chemotherapy

Abstract PurposeCheckMate 743 trial demonstrated survival benefit of immunotherapy in first line in MPM with some differences in the efficacy of chemotherapy according to histology. The objective of this study is to characterize the impact of chemotherapy according to histology in patients diagnosed with MPM at our institution. MethodsClinical records of all MPM patients diagnosed at Vall d´Hebron University Hospital between November 2002 and April 2020 were reviewed. Associations between clinical variables and outcomes were assessed with Cox regression models. Survival data were calculated by the Kaplan-Meier method. Results189 patients were included with 76% of tumors classified as epithelioid subtype. First line chemotherapy was offered to 85% of patients. Median survival in overall population was 21.3 months (95%CI17.2-24.3). We found that patients with epithelioid tumors had better overall survival (OS) and progression free survival (PFS). Median OS of epithelioid patients treated with first line chemotherapy was 26.7 months versus 15.0 months in nonepithelioid patients (HR2.25 CI95% 1.4-3.4; p<0.001). Median PFS for patients with epithelioid tumors treated with chemotherapy was 4.8 months versus 3.6 months in nonepithelioid (HR1.5 CI95% 1.0-2.3; p=0.03). The improvement of outcomes in patients with epithelioid histology was detected in patients treated with cisplatin or carboplatin. Histology was not a predictive factor for the platinum agent sensitivity (p of interaction PFS=0.09, p of interaction OS=0.65). Conclusions In our series, patients with nonepithelioid tumors presented worse prognosis. Although epithelioid tumors exposed to cisplatin had higher PFS, histology was not a clear predictor of chemotherapy efficacy.

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.

Pretreatment skeletal muscle depletion as an adverse prognostic factor in metastatic gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 161-161
Author(s):  
Hiroko Hasegawa ◽  
Kazumasa Fujitani ◽  
Yusuke Yamaoka ◽  
Motohiro Hirao ◽  
Shoichi Nakazuru ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Skeletal Muscle ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Performance Status ◽  
Metastatic Gastric Cancer ◽  
First Line ◽  
Skeletal Muscle Index ◽  
Pre Treatment ◽  
The Impact

161 Background: Body composition has emerged as an important prognostic factor in cancer patients. Especially, skeletal mass depletion has been associated with poor performance status, toxicity of chemotherapy and shortened survival in cancer patients. However, the impact of pre-treatment skeletal muscle index on survival or toxicity in metastatic gastric cancer patients remains uncertain. Methods: In this retrospective study, we reviewed 98 metastatic gastric cancer (mGC) patients who received S-1 based combination chemotherapy as first-line treatment from April 2006 to March 2013. Pre-treatment skeletal muscle mass was quantified by CT cross sectional area at the third lumbar vertebrae and evaluated as lumbar skeletal muscle index (SMI) (cm2/m2) after normalization for stature (m2). Patients were categorized into 2 groups depending on initial SMI: 35 patients with SMI ≤ 40 and 63 patients with SMI > 40. Results: Median overall survival was significantly shorter in the SMI ≤ 40 group than in the SMI >40 group (439 days versus 565 days; p= 0.03). Progression free survival was also better in the SMI> 40 group without statistical significance (175 days versus 151 days; p= 0.17). Toxicity (grade 3 or 4) was more common in the SMI ≤ 40 group than in the SMI >40 group. (41.1% versus 11.1%; p=0.001). In multivariate analysis, performance status of 2 (HR 4.711, 95%CI 1.065 to 20.832, p=0.04), presence of primary tumor (HR 2.322, 95%CI 1.007 to 5.357, p=0.04) and pre-treatment SMI (HR 2.525, 95%CI 1.145 to 5.568, p=0.02) were independent prognostic factors for OS. Conclusions: The present study suggests that skeletal muscle depletion at the initiation of first-line chemotherapy might be an independent prognostic factor for mGC patients.

Muscle volume loss after the induction of first-line chemotherapy as a novel prognostic factor in metastatic colorectal cancer patients.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 558-558
Author(s):  
Yusuke Yoshikawa ◽  
Koji Okabayashi ◽  
Hirotoshi Hasegawa ◽  
Masashi Tsuruta ◽  
Ryo Seishima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Tumor Response ◽  
Muscle Volume ◽  
Oncologic Outcomes ◽  
Volume Loss ◽  
First Line ◽  
The Impact ◽  
Line Chemotherapy

558 Background: Muscle volume loss (MVL) is observed in end-stage cancer patients as cachexia. However, the impact of MVL on tumor response and survival still remains unclear during chemotherapy in metastatic colorectal cancer (mCRC) patients. The aim of this study is to evaluate correlation between MVL and oncologic outcomes in mCRC patients. Methods: A total of 91 mCRC patients who received first-line chemotherapy were identified in our prospective registry between February 2007 and April 2013. Skeletal muscle index at the level of L3 vertebra (SMI) was calculated by muscle volume normalized by stature at the time of the induction of first-line chemotherapy (bSMI) and first evaluation of tumor response (fSMI). Patients whose SMI decreased more than 10% were classified as MVL group. The impact of these variables on oncologic outcomes (overall survival [OS], progression free survival [PFS], and tumor response rate [RR]) were analyzed. Results: Mean bSMI and fSMI were 35.0 (SD: 7.11) cm2/m2, and 34.2 (SD: 6.85) cm2/ m2, respectively. Eighteen patients were classified into the MVL group. The patients in MVL group significantly responded to the chemotherapy (RR of MVL: 11.1% vs. RR of non-MVL: 49.3%, p < 0.01). There was no significant difference in terms of high grade adverse effect between MVL and non-MVL group. Patients in MVL group had a significant shorter median PFS (MVL: 5.5 [2.5 - 10.1] months vs. non-MVL: 12.8 (3.8-80.5) months, p < 0.01) and median OS (MVL: 13.9 [6.2-61.2] months vs. non-MVL: 29.3 (8.2-94.0) months, p < 0.01). Multivariate analysis demonstrated that patients with MVL had significantly worse prognostic factor (OS: HR 3.51 [1.99-6.21], p < 0.01 and PFS: HR 8.27 [2.91-23.5], p < 0.01. Conclusions: The findings of this study suggested that MVL after the induction of the first line chemotherapy could be a novel predictive factor for chemotherapy response and prognosis. Further investigation should be required to clarify the mechanistic background.

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.

scholarly journals Drug Holidays and Overall Survival of Patients with Metastatic Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3504
Author(s):  
Silvio Ken Garattini ◽  
Debora Basile ◽  
Marta Bonotto ◽  
Elena Ongaro ◽  
Luca Porcu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cox Regression ◽  
University Hospital ◽  
Continuous Treatment ◽  
First Line ◽  
Attrition Rates ◽  
Treatment Interruptions ◽  
The Impact

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni- and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni- and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22–2.32; p = 0.002 and HR,4.89; 95% CI, 3.33–7.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer.

Improved Survival in Peripheral T-Cell Lymphoma (PTCL) Following Complete Response to First-Line Chemotherapy: 10 Year Experience at the Royal Marsden and the Christie Hospitals 2002-2012

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1499-1499
Author(s):  
Mary Gleeson ◽  
Kim Linton ◽  
Clare Peckitt ◽  
Adam Gibb ◽  
Eliza A Hawkes ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
P Value ◽  
First Line ◽  
Post Induction ◽  
The Impact ◽  
Line Chemotherapy

Abstract Introduction: PTCL is a rare and heterogeneous group of non-Hodgkin lymphoma (NHL) comprising ~10% of cases. CHOP is frequently used first-line, but with the exception of ALK+ anaplastic large-cell lymphoma (ALCL), long term outcomes are historically poor with reported 5-yr overall survival (OS) rates of 36%. We retrospectively evaluated the outcomes following first-line chemotherapy for patients with PTCL treated at the Royal Marsden (RM) and Christie (CH) hospitals over a 10-year period. Methods: All eligible patients with PTCL aged ≥18 years and treated at the RM and CH between 1st January 2002 and 31st January 2012 were included. The study was approved by our institutional review boards. Patients were identified from hospital databases and included if they had received at least 1 cycle of first-line chemotherapy. Precursor T-cell malignancies, mycosis fungoides and adult T-cell leukaemia/lymphoma were excluded, as was cutaneous T-cell lymphoma not requiring combination chemotherapy. Clinical data were collated from electronic patient records and the diagnosis of PTCL was confirmed in all cases by an expert haematopathologist. Response was assessed using the IWG 1999 criteria. OS and progression free survival (PFS) were calculated from date of start of 1st line treatment and analysed using Kaplan Meier methods and Cox regression model. The impact of clinical factors on survival was assessed using Cox regression analysis. Results: A total of 143 (RM n=69, CH n=74)patients were evaluable and the median follow-up was 63.4 months. The median age at diagnosis was 59 yrs (range 18-89 yrs). PTCL subtypes were: PTCL not otherwise specified (NOS) (n=48), angioimmunoblastic T-cell lymphoma (AITL) (n=37), ALCL ALK- (n=24), ALCL ALK+ (n=14) and other (n=20). First-line chemotherapy included CHOP (n=97), GEM-P (gemcitabine, cisplatin and methylprednisolone) (n=16), other gemcitabine containing regimen (n=7), asparaginase (n=2) or other (n=21). OS by PTCL subtype is shown in Figure 1. Response was evaluable for 125/143 patients. Overall response (ORR) to first-line chemotherapy was 81.4% with complete response (CR) seen in 42.4%. For the entire cohort (n=143) 5-yr PFS was 20.6% and 5-yr OS was 39.6%. For CHOP treated patients ORR was 80.5% with CR in 43.7%, 5-yr PFS was 25.5% and 5-yr OS was 41.2%. ORR with GEM-P was 78.6% with CR in 50%, 5-yr PFS was 13.6% and 5-yr OS was 39.1%. No statistically significant difference between CHOP and GEM-P was seen in terms of response, OS or PFS. Autologous stem cell transplantation (autoSCT) was performed post first-line induction in 15% (n=22). For patients in CR post induction (CR1) (n=41), we compared survival for those treated with (n=12) and without (n=29) subsequent autoSCT. AutoSCT in CR1 was associated with a trend towards better PFS (HR 0.36, 95%CI 0.13-1.02; p=0.056) but not OS (HR 0.72, 95% CI 0.21-2.47; p=0.599). Uni- (UVA) and multivariate analyses (MVA) were performed to determine the impact of the following on OS and PFS: age (≤60 vs > 60yrs), gender, stage (I-III vs IV), performance status (PS, 0-1 vs 2), B symptoms (present vs absent), ethnicity (white vs other), LDH (normal vs elevated), IPI (low vs intermediate vs high), PTCL subtype, number of extranodal sites (0-1 vs >1), chemotherapy (CHOP vs gemcitabine based vs other), CR post induction (present vs absent) and autoSCT (performed vs not). Factors with a p-value of <0.1 in UVA were entered into MVA and independently significant risk factors (p<0.05) are shown in Table 1. Conclusion: With the exception of ALK+ ALCL, outcomes for PTCL following first-line chemotherapy remain disappointing and a more effective induction regimen is urgently required. Our data indicates that achieving a CR with first-line induction is a key factor for optimising OS and PFS. To this end, the currently accruing UK NCRI randomised phase II CHEMO-T study is comparing CHOP with GEM-P as first-line regimens in PTCL. AutoSCT in CR1 may offer a PFS benefit and should be considered in eligible patients. Table 1. MVA for OS and PFS (n=104) Risk Factor HR 95% CI p-value OS Intermediate risk IPI 4.56 1.79-11.6 0.001 High risk IPI 12.0 4.32-33.1 <0.001 CR post induction 0.36 0.21-0.64 <0.001 PFS Female sex 0.33 0.19-0.58 <0.001 Intermediate risk IPI 3.17 1.61-6.24 0.001 High risk IPI 7.76 3.35-17.6 <0.001 CR post induction 0.36 0.22-0.60 <0.001 AutoSCT post induction 0.30 0.13-0.66 0.003 Figure 1. OS according to PTCL subtype Figure 1. OS according to PTCL subtype Disclosures Chau: Roche: Research Funding. Cunningham:Merrimack: Research Funding; Bayer HealthCare Pharmaceuticals: Research Funding; Medimmune: Research Funding; Astra Zeneca: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Merck Serono: Research Funding; Sanofi: Research Funding.

scholarly journals A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 168
Author(s):  
Gil Awada ◽  
Yanina Jansen ◽  
Julia Katharina Schwarze ◽  
Jens Tijtgat ◽  
Lennert Hellinckx ◽  
...  
Keyword(s):  
Survival Data ◽  
Cox Regression ◽  
Clinical Laboratory ◽  
Performance Status ◽  
Stage Iv ◽  
Absolute Lymphocyte Count ◽  
Comprehensive Analysis ◽  
Advanced Melanoma ◽  
University Hospital ◽  
Cox Regression Analysis

Background: Pembrolizumab improves the survival of patients with advanced melanoma. A comprehensive analysis of baseline variables that predict the benefit of pembrolizumab monotherapy has not been conducted. Methods: Survival data of patients with advanced melanoma who were treated with pembrolizumab in a single university hospital were collected. A multivariate Cox regression analysis was performed to correlate baseline clinical, laboratory, and radiologic characteristics and NanoString IO360 gene expression profiling (GEP) with survival. Results: 183 patients were included (stage IV 85.2%, WHO performance status ≥1 31.1%; pembrolizumab first-line 25.7%), of whom 112 underwent baseline 18F-FDG-PET/CT imaging, 58 had circulating tumor DNA (ctDNA) assessments, and GEP was available in 27 patients. Active brain metastases, a higher number of metastatic sites, lower albumin and absolute lymphocyte count (ALC), higher C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio, higher total metabolic tumor volume (TMTV), and higher ctDNA levels were associated with worse survival. Elevated lactate dehydrogenase (LDH) ≥ 2ULN (upper limit of normal), CRP ≥ 10ULN, or ALC < 750/mm3 delineate a subpopulation where treatment with pembrolizumab is futile. A TMTV ≥ 80 mL encompassed 17/21 patients with LDH ≥ 2ULN, CRP ≥ 10ULN, or ALC < 750/mm3. No significant associations were observed between baseline GEP scores and survival. Conclusion: Multiple baseline variables correlate with survival on pembrolizumab. TMTV is a more comprehensive baseline biomarker than CRP, LDH, or ALC in predicting the futility of pembrolizumab.

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