scholarly journals Prediction of patients with a tumor proportion score >50% who do not respond to first-line monotherapy with pembrolizumab

2020 ◽  
Author(s):  
Mitsunori Morita ◽  
Motohiro Tamiya ◽  
Daichi Fujimoto ◽  
Akihiro Tamiya ◽  
Hidekazu Suzuki ◽  
...  

Abstract Background: Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50%. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown. Methods: We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) >50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data. Results: A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N=52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥2 (p=0.0832), stage IV disease or recurrence (p=0.0487), PD-L1 TPS 50–89% (p=0.0657), use of steroids prior to the administration of pembrolizumab (p=0.0243), malignant pleural effusion (p=0.0032), and baseline C-reactive protein (CRP) levels >1.0 mg/dL (p=0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p=0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p=0.0228), and baseline CRP >1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p=0.0402) were significantly associated with non-response to treatment. Conclusion: In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels >1.0mg/dL reduced the response of first-line monotherapy with pembrolizumab.

2019 ◽  
Author(s):  
Mitsunori Morita ◽  
Motohiro Tamiya ◽  
Daichi Fujimoto ◽  
Akihiro Tamiya ◽  
Hidekazu Suzuki ◽  
...  

Abstract Background: Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50%. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown. Methods: We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) >50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data. Results: A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N=52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥2 (p=0.0832), stage IV disease or recurrence (p=0.0487), PD-L1 TPS 50–89% (p=0.0657), use of steroids prior to the administration of pembrolizumab (p=0.0243), malignant pleural effusion (p=0.0032), and baseline C-reactive protein (CRP) levels >1.0 mg/dL (p=0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p=0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p=0.0228), and baseline CRP >1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p=0.0402) were significantly associated with non-response to treatment. Conclusion: In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels >1.0mg/dL reduced the effectiveness of first-line monotherapy with pembrolizumab.


2019 ◽  
Author(s):  
Mitsunori Morita ◽  
Motohiro Tamiya ◽  
Daichi Fujimoto ◽  
Akihiro Tamiya ◽  
Hidekazu Suzuki ◽  
...  

Abstract Background: Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50%. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown. Methods: We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) >50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data. Results: A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N=52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥2 (p=0.0832), stage IV disease or recurrence (p=0.0487), PD-L1 TPS 50–89% (p=0.0657), use of steroids prior to the administration of pembrolizumab (p=0.0243), malignant pleural effusion (p=0.0032), and baseline C-reactive protein (CRP) levels >1.0 mg/dL (p=0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p=0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p=0.0228), and baseline CRP >1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p=0.0402) were significantly associated with non-response to treatment. Conclusion: In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels >1.0mg/dL reduced the effectiveness of first-line monotherapy with pembrolizumab.


2020 ◽  
Author(s):  
Mitsunori Morita ◽  
Motohiro Tamiya ◽  
Daichi Fujimoto ◽  
Akihiro Tamiya ◽  
Hidekazu Suzuki ◽  
...  

Abstract Background: Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50%. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown. Methods: We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) >50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data. Results: A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N=52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥2 (p=0.0832), stage IV disease or recurrence (p=0.0487), PD-L1 TPS 50–89% (p=0.0657), use of steroids prior to the administration of pembrolizumab (p=0.0243), malignant pleural effusion (p=0.0032), and baseline C-reactive protein (CRP) levels >1.0 mg/dL (p=0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p=0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p=0.0228), and baseline CRP >1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p=0.0402) were significantly associated with non-response to treatment. Conclusion: In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels >1.0mg/dL reduced the response of first-line monotherapy with pembrolizumab.


2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 197-197
Author(s):  
Sameer Ghate ◽  
Jackson Tang ◽  
Zhiyi Li ◽  
Antonio Reis Nakasato

197 Background: For patients (pts) with metastatic melanoma (MM) and BRAF V600 mutation (BRAF+), options for first-line (1L) systemic combination therapy include immunotherapy (IO) or targeted therapy (TT). This study describes real world treatment patterns among BRAF+ MM pts treated with 1L ipilimumab+nivolumab (I+N) or dabrafenib+trametinib (D+T). Methods: This retrospective observational analysis used Flatiron Health’s electronic health record-derived database from Oct 2015 - Jul 2016. Oct 2015 was chosen as the start date as both combo use of I+N and D+T had been approved by the FDA. Pts were aged ≥18 years with a MM diagnosis, tested BRAF+ prior to therapy, and treated with either I+N or D+T as 1L therapy. Baseline demographic and clinical characteristics, and treatment patterns were collected from structured data and unstructured data in physician notes, and were descriptively assessed. Kaplan-Meier (KM) analysis measured time to discontinuation. Statistical inferences were not planned in this study. Results: Among 76 BRAF+ pts, 62% (47) were treated with D+T as 1L, and 38% (29) were treated with I+N as 1L. Compared to D+T pts, lower proportion of I+N pts had a history of brain metastases (31% vs. 34%) and elevated ( > 333 IU/L) lactate dehydrogenase (10% vs. 19%), while a higher proportion of I+N pts reported ECOG performance status score of zero (38% vs. 23%). The two cohorts were similar in age, gender and baseline comorbidities. Discontinuation among D+T and I+N was 43% (20) and 48% (14) respectively. The primary reason for discontinuation was progression among D+T pts (10/20) vs. toxic effects of therapy among I+N pts (8/14). KM median time to discontinuation was 213 days for D+T pts vs. 196 days for I+N pts. 55% of I+N pts did not complete full induction of 4 doses of ipilimumab, citing toxic effects of therapy. Conclusions: 1L D+T patients had higher tumor burden, elevated LDH levels, and higher ECOG performance status score, but lower discontinuation rate and longer time to treatment discontinuation relative to BRAF+ 1L I+N pts.


Author(s):  
Eiji Takeuchi ◽  
Yoshio Okano ◽  
Hisanori Machida ◽  
Katsuhiro Atagi ◽  
Yoshihiro Kondou ◽  
...  

Abstract Objective Tumor-related eosinophilia may have extended survival benefits for some cancer patients. However, there has been no report on the prognosis difference between eosinophilic pleural effusion (EPE) and non-EPE in lung cancer patients. Our study aimed to investigate the prognosis difference between EPE and non-EPE due to lung cancer. Patients and methods We retrospectively reviewed patients diagnosed with lung cancer who presented with malignant pleural effusion (MPE) between May 2007 and September 2020 at the National Hospital Organization Kochi Hospital. EPE is defined as pleural fluid with a nucleated cell count containing 10% or more eosinophils. Results A total of 152 patients were included: 89 were male (59%). The median age was 74.4 years (range 37–101), and all patients were pathologically shown to have MPE. Most patients (140; 92%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0/1. Twenty patients had EPE. The median overall survival (OS) of all 152 lung cancer patients with MPE was 298 days. The median OS of the patients with EPE was 766 days, and the median OS of the patients with non-EPE was 252 days. Kaplan–Meier univariate analysis showed that lung cancer patients with EPE had a significantly better prognosis than patients with non-EPE (P < 0.05). Cox proportional regression analysis showed that EPE, ECOG PS, sex, and the neutrophil-to-lymphocyte ratio in the serum (sNLR) may be independent prognostic factors affecting survival in patients with MPE. Conclusion Lung cancer patients with EPE have a better prognosis than those with non-EPE.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21666-e21666
Author(s):  
Fernando Abrao ◽  
Mariana Campello de Oliveira ◽  
Igor Abreu ◽  
Geisa Garcia ◽  
Renata D'Alpino D'Alpino ◽  
...  

e21666 Background: The aim of this study was to identify predictors of overall survival (OS) and recurrence after palliative pleural procedures in patients with malignant pleural effusion (MPE) and high-risk tumors according to the LENT Score. Methods: Data was collected from our database between January 2013 and December 2015 of patients with MPE and high-risk tumors according to the LENT Score. All patients were followed-up for at least 30 days after the pleural procedure. We evaluated radiological aspects, biochemical and hematologic parameters as well as clinical features. For OS analysis, patients were divided into two groups. Group I included OS < 30 days and group II included OS > 30 days. Prognostic factors for pleural recurrence and OS were identified by univariate analysis, using Fisher's exact and Student's t-test. Subsequently, significant variables were entered into a multivariate logistic regression analysis ( p < 0.05). Results: A total of 134 patients were included. Median follow-up time for surviving patients was 56 (range: 2-623) days. High-risk primary tumors included lung (66.4%), gastrointestinal (24.6%) , sarcoma (3.7%), urologic (3.7%) and others (1.5%). Forty-four patients in Group I had OS < 30 days while 22 patients had MPE recurrence. Factors affecting OS in univariate analysis were: type of procedure, ECOG, albumin, leukocytes, neutrophil to lymphocyte ratio( NRL) and hemoglobin. Factors affecting recurrence were: type of procedure, chemotherapy line (CT), albumin and platelets. In multivariate analysis for Group I, type of procedure (therapeutic pleural aspiration – TPA) ( p= 0.011), ECOG 3/4 ( p= 0.004), NLR > 5 ( p= 0.037) and leukocytes > 8000 ( p= 0.042) were identified as independent predictors of OS. In terms of recurrence, only CT beyond first line ( p = 0.042) was identified as an independent prognostic factor. Conclusions: Patients with MPE who underwent TPA, had ECOG 3/4, leukocytes > 8000, and NLR > 5 were significantly associated with shorter OS,. CT beyond first line was associated with recurrence. The identification of these prognostic factors may assist physicians in choosing the optimal palliative technique.


2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Gabrielle Drevet ◽  
Jean-Michel Maury ◽  
Naoual Bakrin ◽  
François Tronc

AbstractObjectivesMalignant pleural effusion (MPE) is a devastating evolution of several malignancies. Pressurized intrathoracic aerosol chemotherapy (PITAC) might be a novel therapy option in MPE.MethodsPITAC is considered for patients with MPE with a performance status <2 and without other metastatic sites. General anesthesia is administered and a double-lumen bronchial tube is inserted. The patient is placed in a lateral decubitus position, and the operation is performed after ipsilateral lung exclusion. Two 12-mm balloon trocars are inserted—one in the seventh intercostal space in the mid-axillary line and one in the fifth intercostal space in the anterior axillary line. Extent of pleural disease and volume of MPE are documented. MPE is removed and parietal pleural biopsy are performed. An intrathoracic pressure of 12 mmHg CO2 is established, and a combination of Cisplatin (10.5 mg/m2 in a total volume of 150 cc NaCl 0.9%) and Doxorubicin (2.1 mg/m2 in a total volume of 50 cc NaCl 0.9%) are aerosolized via nebulizer in the pleural cavity. Vital signs and nebulization are remote-controlled. After 30 min, the remaining toxic aerosol is exhausted using a closed surgical smoke evacuation system. A 24Fr chest tube is inserted in postero-apical position with continuous negative pressure of 20 cm H2O. When needed, PITAC may be repeated every six weeks in alternate with systemic chemotherapy.ResultsIn our hands, the technique above has shown to be feasible and safe.ConclusionsFurther studies are needed to assess the potential symptomatic and oncological benefits of PITAC in MPE.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A448-A448
Author(s):  
Johann De Bono ◽  
Neal Shore ◽  
Gero Kramer ◽  
Anthony Joshua ◽  
Xin Tong Li ◽  
...  

BackgroundTreatment-emergent neuroendocrine prostate carcinoma (t-NE) can occur de novo or after diagnosis of prostate adenocarcinoma. Treatment often includes platinum-containing chemotherapy because of t-NE’s histologic similarity to small cell lung cancer. The PD-1 inhibitor pembrolizumab has shown promising efficacy and acceptable safety when combined with olaparib, docetaxel, or enzalutamide for treatment of metastatic castration-resistant prostate cancer (mCRPC) in the multicohort phase 1b/2 KEYNOTE-365 study (NCT02861573). Cohort I will be used to compare platinum-containing chemotherapy alone with chemotherapy + pembrolizumab as treatment for t-NE.MethodsPatients who have t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review); experienced progression within 6 months of starting a next-generation hormonal agent (NHA) for mCRPC or hormone-sensitive prostate cancer and experienced progression within 6 cycles of docetaxel treatment for mCRPC; and have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 are eligible. Prior therapy with ≤2 NHAs and 1 other chemotherapy for mCRPC is permitted. Patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg IV on day 1 of each cycle every 3 weeks + carboplatin AUC of 5 IV on day 1 + etoposide 100 mg/m2 IV on days 1, 2, and 3 of each 21-day cycle for 4 cycles (arm 1) or the same chemotherapy regimen without pembrolizumab (arm 2); in each arm 40–100 patients will be enrolled. Pembrolizumab treatment will continue up to 2 years until disease progression, unacceptable toxicity, or withdrawal of consent. Patients will be stratified by ECOG performance status score (0 or 1). Computed tomography or magnetic resonance imaging will be performed every 9 weeks through week 54 and every 12 weeks thereafter. Primary end points are safety and tolerability, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points are time to PSA progression; ORR and radiographic progression-free survival (PFS) per PCWG3-modified RECIST v1.1 by BICR; duration of response and disease control rate per RECIST v1.1 by BICR and PCWG3-modified RECIST v1.1 by BICR; and overall survival. End points will be summarized for each arm without formal hypothesis testing.AcknowledgementsMedical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicaltrials.gov, NCT02861573Ethics ApprovalThe study and the protocol were approved by the Institutional Review Board or ethics committee at each site.


2013 ◽  
Vol 119 (4) ◽  
pp. 871-877 ◽  
Author(s):  
Dale Ding ◽  
Zhiyuan Xu ◽  
Ian T. McNeill ◽  
Chun-Po Yen ◽  
Jason P. Sheehan

Object Parasagittal and parafalcine (PSPF) meningiomas represent the second most common location for intracranial meningiomas. Involvement of the superior sagittal sinus or deep draining veins may prevent gross-total resection of these tumors without significant morbidity. The authors review their results for treatment of PSPF meningiomas with radiosurgery. Methods The authors retrospectively reviewed the institutional review board–approved University of Virginia Gamma Knife database and identified 65 patients with 90 WHO Grade I parasagittal (59%) and parafalcine (41%) meningiomas who had a mean MRI follow-up of 56.6 months. The patients' mean age was 57 years, the median preradiosurgery Karnofsky Performance Status score was 80, and the median initial tumor and treatment volumes were 3 and 3.7 cm3, respectively. The median prescription dose was 15 Gy, isodose line was 40%, and the number of isocenters was 5. Kaplan-Meier analysis was used to determine progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to identify factors associated with PFS. Results The median overall PFS was 75.6 months. The actuarial tumor control rate was 85% at 3 years and 70% at 5 years. Parasagittal location, no prior resection, and younger age were found to be independent predictors of tumor PFS. For the 49 patients with clinical follow-up (mean 70.8 months), the median postradiosurgery Karnofsky Performance Status score was 90. Symptomatic postradiosurgery peritumoral edema was observed in 4 patients (8.2%); this group comprised 3 patients (6.1%) with temporary and 1 patient (2%) with permanent clinical sequelae. Two patients (4.1%) died of tumor progression. Conclusions Radiosurgery offers a minimally invasive treatment option for PSPF meningiomas, with a good tumor control rate and an acceptable complication rate comparable to most surgical series.


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