Plasma biomarkers to predict pembrolizumab response in HCC patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14043-e14043
Author(s):  
Lynn G. Feun ◽  
Ying-Ying Li ◽  
Chunjing Wu ◽  
Medhi Wangpaichitr ◽  
Patricia Denise Jones ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Progression Free Survival ◽  
Complete Response ◽  
Second Line Therapy ◽  
Free Survival ◽  
Clinical Biomarkers ◽  
Kaplan Meier ◽  
Ifn Γ ◽  
The Mean ◽  
Circulating Levels

e14043 Background: Pembrolizumab (PEM) has been approved as second line therapy for the treatment of hepatocellular carcinoma (HCC). We conducted a single institution investigator-initiated clinical/biomarkers trial to assess potential biomarkers to predict response in unresectable HCC patients (pts) receiving PEM. Methods: PEM was administered at 200mg iv. every 3 weeks for advanced HCC pts who progressed on, were intolerant of, or refused sorafenib. The circulating levels of cytokines/chemokines included IL-1β, IL-6, IL-8, IL-12, IL-18, IFN-γ, TGF-β, IL-10, CXCL9, CCL4, CCL5, as well as PD-1, PD-L1, PD-L2 were measured by ELISA at baselines and at day 60-90. PD-L1 expression in tumor was also assessed by histopathological staining. Results: 29 pts have been treated and 28 were evaluated for response. One pt had complete response, 8 had partial response and 4 had stable disease. Among all the biomarkers tested, only TGF-β at baseline predict response. The mean of plasma TGF-β in responders were 141.9pg/ml vs. 1071.8pg/ml in nonresponders. The cut-off values was determined based on the near medians. The plasma concentration of TGF-β of ≥200pg/ml was an index for nonresponder (P = 0.003). Kaplan-Meier analysis showed that the median overall survival (OS) and progression-free survival (PFS) in pts with TGF-β ≥200pg/ml were 7 months and 2 months, respectively, while in pts with TGF-β < 200 pg/ml, the OS and PFS were over 25 months(P = 0.005 and P = 0.008, respectively). Plasma IFN-γ or IL-10 levels positively correlated with plasma PD-1/PD-L-1 (P < 0.05). Since tumor PD-L1 expression is upregulated by IFN-γ, and IL-10, and interacts with PD-1 to suppress T cell, to confirm these relationships, the linear regression was used to analyze the data. Plasma IFN-γ or IL-10 levels positively correlated with plasma PD-1 and PD-L1 levels ( P < 0.05). Nine of these 24 patients had tumor available for PD-L1 scoring (PD-L1-positive:3 pts and PD-L1-negative:6pts). Similar to plasma PD-L1 concentration, pts with positive tumor PD-L1 had high levels of plasma IFN-γ or IL-10 ( P < 0.05). Conclusions: Our study confirmed that PEM is active in HCC and TGF-β is a predictive markers for tumor response, PFS, and OS. Support by grant from Merck

scholarly journals Minimal Residual Disease Status Predicts Progression-Free Survival in Newly Diagnosed Multiple Myeloma (NDMM) Patients Treated with Carfilzomib, Lenalidomide, and Low-Dose Dexamethasone (KRd)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2127-2127 ◽  
Author(s):  
Jagoda Jasielec ◽  
Dominik Dytfeld ◽  
Kent A. Griffith ◽  
Kathryn McDonnell ◽  
Daniel Lebovic ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Employment Equity ◽  
Advisory Committees ◽  
Free Survival ◽  
Kaplan Meier ◽  
Equity Ownership ◽  
Minimal Residual

Abstract Background: NDMM patients (pts) treated with KRd in a phase 1/2 trial (NCT01029054) demonstrated high rates of complete response (CR, 64%) and stringent complete response (sCR, 55%) that correlated with excellent estimated 3-year progression-free survival (PFS; 79%) and overall survival (OS; 96%) (Jakubowiak et al, Blood, 2012; Jasielec et al, Blood 2013; 122(21):3220). Furthermore, there was a trend towards superior outcomes in patients with multiparameter flow cytometry (MFC) MRD-negative disease with an estimated 3 year PFS of 84% and OS of 100%, suggesting the importance of MRD analysis in predicting relapse. In this post hoc, retrospective analysis, we present an updated evaluation of PFS based on minimal residual disease (MRD) status. Methods: Pts received 28-day cycles of carfilzomib (CFZ) 20–36 mg/m2 intravenously (days [d]1, 2, 8, 9, 15, 16), lenalidomide (LEN) 25 mg orally (PO; d1–21), and dexamethasone 40/20 mg PO weekly (cycles 1–4/5–8). For cycles 8–24, KRd was given with a modified CFZ schedule (d1, 2, 15, 16), and single-agent LEN was administered after cycle 24. Pts had the option to receive stem cell transplantation after cycle 4. MRD assessment at the time of complete response (CR) was performed using 10-color MFC and next-generation sequencing (NGS) analysis. Fresh bone marrow aspirate (BMA) was used for MFC analysis as previously reported, while archived BMA slides were used for NGS analysis. The LymphoSIGHT™ NGS method employed universal primer sets to assess clonal rearrangements at the immunoglobulin loci (IGH-VDJ, IGH-DJ and IGK) in diagnostic BMA slides. Myeloma clonotypes were identified in the diagnostic BMA sample of each patient based on high-frequency within the B-cell repertoire. The level of the myeloma clonotype was then quantified in BMA slides obtained at the time of CR. Results: Twenty-two pts with CR/sCR were evaluated for MRD by both MFC and NGS methods with a median follow-up of 40 months. Limited input DNA was obtained from BMA slides (range 2,189 to 1,870,960 cell equivalents). Concordance analysis in 21 patients with both MFC and NGS MRD data revealed 11 patients that were MRD-negative by both MFC and NGS, while 2 patients were concordantly MRD-positive. NGS demonstrated greater sensitivity compared to MFC, as 8 patients were MRD-positive by NGS but MRD-negative by MFC. Three of these 8 patients relapsed. We evaluated the correlation between MRD status by NGS and PFS. Six MRD samples had less than 40,000 input cell equivalents and were removed from the progression-free survival analysis due to insufficient sample amount. MRD negativity by NGS in KRd patients at the time of CR was associated with longer progression-free survival (median not reached vs 46 months, p = 0.055) (Figure 1). Conclusions: Our results suggest that achievement of MRD-negative disease by NGS in CR patients is associated with superior PFS. The NGS method appears more sensitive than MFC at detecting residual disease. Finally, MRD assessment by NGS in BMA slides is feasible although may not be the optimal method due to limited input DNA amount. MRD assessment by NGS will be performed on the remainder of the KRd cohort and results will be presented. Figure 1. Kaplan-Meier analysis of progression-free survival for 6 MRD negative (<10-6) and 10 MRD positive (>10-6) patients. Figure 1. Kaplan-Meier analysis of progression-free survival for 6 MRD negative (<10-6) and 10 MRD positive (>10-6) patients. Disclosures Faham: Sequenta, Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Lee:Sequenta, Inc.: Employment, Equity Ownership. Jakubowiak:Bristol Myers-Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SkylineDx: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Timing of last chemotherapy and the end of life in patients (pts) with metastatic cancer.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 59-59
Author(s):  
Marianna Brollo ◽  
Massimo Bratta ◽  
Simona Molinaro ◽  
Giannarelli Diana ◽  
Mariannina Ricci ◽  
...  
Keyword(s):  
End Of Life ◽  
Median Overall Survival ◽  
Chemotherapy Regimen ◽  
Metastatic Cancer ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Free Survival ◽  
Poor Outcome ◽  
Kaplan Meier ◽  
Younger Age

59 Background: Chemotherapy near the end of life is often associated with increased toxicity and poor outcome. The aim of this study was to assess the outcome of patients (pts) with metastatic cancer who received chemotherapy near the end of life. Methods: We conducted an observational, retrospective analysis of 77 consecutive cancer pts (aged ≥ 18 years) who died in hospice between January 2017 and July 2018. Median overall survival (OS) and the 95% confidence interval (CI) were estimated with the Kaplan -Meier method. Results: Of 77 pts (median age: 72 years [y]; male: 59.7%) with metastatic cancer, 51 pts (66.2%) received chemotherapies for metastatic disease (mean prior lines: 2.1 ) and 26 pts (33.8%) received best supportive care (BSC). The most represented histologies were lung (31.2%) and breast (11.7%) cancer. The median time from the last chemotherapy and the death was 67 days. The median progression free survival (PFS) of the last treatment was 45 days. According to Earle’s criteria, 6.5% of pts started a new chemotherapy regimen in the last 30 days of life and 2.6% of subjects received chemotherapy in the last 14 days of life. 11.7% and 3.9% of pts received chemotherapy within the last 30 and 15 days of life, respectively. Younger pts (< 70 years) had an increased probability of continuing chemotherapy within the last 1 month (p=0.004) and < 2 weeks (p=0.002) before death than elderly (> 70 years). Conclusions: This study shows that end-of-life chemotherapy is associated with poor outcome. The use of chemotherapy within 30 and 15 days before death was correlated with younger age.

Analysis of toxicity and clinical outcomes (CO) in full versus reduced dose cabozantinib (cabo) in metastatic renal cell carcinoma (mRCC) patients (pts).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 671-671
Author(s):  
Dylan J Martini ◽  
Julie M. Shabto ◽  
Yuan Liu ◽  
Bradley Curtis Carthon ◽  
Alexandra Speak ◽  
...  
Keyword(s):  
Radiographic Progression ◽  
Clear Cell ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Poor Prognostic Factor ◽  
Free Survival ◽  
Reduced Dose ◽  
Kaplan Meier

671 Background: The full dose of cabo is 60 mg, but some pts are treated with a reduced dose with the clinical anticipation of adverse events (AEs). We compared AEs and CO in mRCC pts treated with full versus reduced dose cabo. Methods: We performed a retrospective analysis of 65 mRCC pts treated with cabo at Winship Cancer Institute from 2016-2018. CO were measured by overall survival (OS), progression-free survival (PFS), and objective response (OR). OS and PFS were measured from first dose of cabo to date of death and clinical or radiographic progression, respectively. OR was defined as partial response (PR) or complete response (CR) per RECISTv1.1. AEs were collected from clinic notes. Univariate analysis (UVA) of association between AEs and CO was performed using logistic regression model. Results: Most pts were males (68%) and the median age was 63 years. Most (79%) had clear cell RCC (ccRCC) and the majority were IMDC intermediate (59%) or poor (39%) risk. Most pts (68%) received 60 mg and 48% of these pts underwent a dose reduction for AEs. Nearly all pts (95%) who started on a reduced dose experienced AEs, compared to 66% for pts treated with 60 mg. OR rate was similar for pts on 60 mg (18%) and pts on a reduced dose (19%). The median survival was comparable in pts treated with 60 mg and pts treated with a reduced dose (10.9 vs. 8.8 months, p=0.92 for OS and 5.6 vs. 5.1 months, p=0.23 for PFS) per Kaplan Meier estimation. AEs, particularly gastrointestinal (GI) AEs, were associated with significantly lower chance of OR (Table). Conclusions: CO may be comparable in mRCC pts treated with full versus reduced dose of cabo, but a reduced dose of cabo may not be associated with decreased AEs. GI side effects may be a poor prognostic factor in mRCC pts treated with cabo. Larger studies are warranted to validate these findings. [Table: see text]

A phase II trial of durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5582-5582 ◽  
Author(s):  
Maria M Rubinstein ◽  
Imogen Caird ◽  
Qin Zhou ◽  
Alexia Iasonos ◽  
Claire Frances Friedman ◽  
...  
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Early Death ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Kaplan Meier ◽  
Duration Of Response ◽  
Grade 3 ◽  
Modest Activity ◽  
Clinical Trial Information

5582 Background: Monoclonal antibodies Durvalumab (D) and Tremelimumab (T) inhibit binding of programmed cell death ligand 1 (PDL1) to PD1 and inhibit activation of cytotoxic T-lymphocyte-associated protein 4 (CTLA4), respectively, resulting in improved tumor immunosurveillance. There is rationale to study D and DT based on recent genomic and tumor microenvironment evaluation of endometrial cancer (EC). Methods: Eligible patients (pts) were randomized to D or DT. Pts received D 1500 mg intravenously (IV) every 4 weeks (wks). DT therapy pts received D 1500 mg IV every 4 wks and T 75 mg IV every 4 wks for 4 cycles, followed by D 1500 mg IV every 4 wks until progression or unacceptable toxicities. Pts were stratified by histology with 10 carcinosarcoma or MSI-H EC pts per arm. Efficacy assessments were every 8 wks and treatment related adverse events (TRAEs) were assessed per CTCAE v.4.03. The primary endpoint was overall response rate (ORR) by RECIST v1.1. Descriptive statistics and 90% one sided CI are reported. Progression free survival (PFS) rate at 24 wks (PFS24wks) was estimated by Kaplan Meier method. Results: At planned interim analysis, 56 pts were enrolled (28 per arm). 15 pts: carcinosarcoma, 15 pts: endometrioid (3: Gr1), 14 pts: serous, and 12 pts: other histology. 5(9%) pts: MSI-H, 48(86%) pts: microsatellite stable (MSS), 3(5%): unknown. 2 pts were excluded due to early death. 27 pts per arm were evaluable for efficacy. In the D arm: 1 pt had complete response (CR)(MSS) and 3 pts had a partial response (PR) (2:MSS, 1:MSI-H) with an ORR of 14.8% (CI: 6.6-100%). The median PFS was 7.6 wks and PFS24wks was 13.3% (CI 6.1-100%). Median duration of response (DOR) was 16 wks in the D arm. In the DT arm, 2 pts achieved CR (1:MSI-H, 1:MSS) and 1 had PR (MSS). The ORR was 11.1% (CI: 4.2-100%). Median PFS was 8.1 wks, PFS24wks was 18.5% (CI 10.1-100%) and DOR was 8 wks. Grade 3 TRAEs occurred in 2 (7%) pts in D and 9 (32%) pts in DT. Grade 4 TRAEs occurred 1 (4%) pt in D and 3 (11%) pts in DT. 2 pts discontinued due to a TRAE. Most common TRAEs in total were fatigue (23%), diarrhea (20%), nausea (14%), vomiting (13%) and pruritis (11%). Conclusions: D and DT show modest activity in EC. No new safety signals were identified. Second stage accrual is ongoing. Clinical trial information: NCT03015129.

scholarly journals Outcomes and issues of 12 chordomas treated in a single center

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Maria Karampouga ◽  
Fotis Tsetsos ◽  
Pavlos Sakellariou ◽  
Ioannis Baltas
Keyword(s):  
Progression Free Survival ◽  
Conformal Radiotherapy ◽  
Time Lapse ◽  
Subtotal Resection ◽  
Low Grade ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Mean ◽  
Mean Time ◽  
Shed Light

Abstract Background Chordomas stem from notochordal vestiges and rank as low-grade bone malignancies although fraught with high risk of recurrence. This study assesses the clinical outcomes of twelve chordoma cases treated in our clinic, in an effort to shed light on the often under-represented pool of results deriving from non-referral centers. Methods We reviewed the clinicopathological traits of all chordoma patients registered in our center since 1991. Major endpoints were overall survival (OS) and progression-free survival (PFS) estimated using the Kaplan–Meier and Nelson–Aalen methods. Results Twelve patients, aged on average 47.9 years, were treated for primary or recurrent disease. Seven had chordomas originating in the cranium, 5 in the spine, including a bifocal tumor, and the mean time lapse between the beginning of symptoms and diagnosis was 15.4 months, marked by dull ache. Subtotal resection was achieved in 5 cases, incomplete in 5, while in 2, only biopsy was accomplished. Conformal radiotherapy was administered to 5 and stereotactic radiosurgery to 2 in the setting of recurrence. Protons were used once and targeted agents induced no clinical response in 3 patients. Median OS and PFS were 36 and 12 months, respectively, with the best outlook linked to maximal resection, spinal location, and good preoperative functional status. In all, 6 patients died of chordoma, 4 are alive, and 1 was lost. Relapse was the rule for most cases, except 2, and pulmonary metastases were ascertained in 1. Conclusions Our cases were typical of chordomas, implying that inadequate surgical margins and successive recurrence are negative determinants of prognosis and that interinstitutional cooperation counterbalances shortages in non-referral institutes.

scholarly journals Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort

2021 ◽  
Author(s):  
Laurie H. Sehn ◽  
Mark Hertzberg ◽  
Stephen S. Opat ◽  
Alex F. Herrera ◽  
Sarit Assouline ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Effective Treatment Option ◽  
Free Survival ◽  
Significant Survival ◽  
End Of Treatment ◽  
Independent Review

Polatuzumab vedotin plus bendamustine and rituximab (pola+BR) received regulatory approvals in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) based on primary results from the randomized arms of the GO29365 study. Following the randomized phase, 106 additional patients received pola+BR in a single-arm extension cohort. We report updated results from the randomized arms, and results of the extension cohort. In this phase Ib/II study, patients with R/R DLBCL who were transplant-ineligible received up to six 21-day cycles of pola+BR or BR. The primary endpoint of the randomized arms was complete response (CR) rate at end of treatment. Primary objectives of the extension cohort were safety, pharmacokinetics, and efficacy of pola+BR. As of July 7, 2020, 192 patients with R/R DLBCL were enrolled into pola+BR cohorts (n=152 [safety run-in: n=6; randomized: n=40; extension cohort: n=106]) or the BR cohort (n=40). Significant survival benefit with pola+BR versus BR persisted in the randomized arms (median progression-free survival [PFS]: 9.2 vs 3.7 months, hazard ratio [HR]: 0.42, 95% confidence interval [CI] 0.25-0.71 months; median overall survival [OS]: 12.4 vs 4.7 months, HR: 0.42, 95% CI 0.24-0.72 months). In the extension cohort, the independent review committee (IRC)-assessed objective response rate was 41.5% and CR rate was 38.7%; median IRC-assessed PFS and OS were 6.6 months and 12.5 months, respectively. No new safety signals with pola+BR were identified. Pola+BR is an effective treatment option for patients with R/R DLBCL, with a well-characterized and manageable safety profile. ClinicalTrials.gov: NCT02257567.

scholarly journals Ablación Por Radiofrecuencia De Metástasis Pulmonares: Experiencia Del Instituto Oncológico Nacional De Panamá

2018 ◽  
Vol 1 (38) ◽  
Author(s):  
José Pinto-Llerena ◽  
Hector Tapia ◽  
Maylin Ruíz ◽  
Omar Castillo-Fernandez
Keyword(s):  
Response Rate ◽  
Lung Metastases ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Short Term ◽  
Free Survival ◽  
Kaplan Meier ◽  
Permanent Loss ◽  
One Year

<p>[Radiofrequency ablation of lung metastases: experience of National Cancer Institute of Panama]</p><p>Resumen<br />Introducción: La evidencia de la metastasectomía quirúrgica es poca y sin estudios aleatorizados. Morbilidad a corto plazo que puede ser responsable por pérdida de función permanente y con aumento de costos. En base a esto surge la necesidad de terapias de control local en pacientes que no podían ser sometidos a metastasectomía. Metodología: realizamos una revisión retropectiva de todos los pacientes tratados en el Instituto Oncológico Nacional de Panamá con ARF pulmonar entre 2013 a 2018. Se estudiaron variables demográficas, clínicas, terapéuticas y pronósticas. El método de Kaplan-Meier fue utilizado para analizar la supervivencia libre de progresión y supervivencia global. Resultados: Se analizaron 31 pacientes, la mediana de edad fue de 63 años, 54.8 % de sexo femenino. Los sitios primarios más frecuentes fueron colon, mama y recto. La mayoría con ECOG 1 y 1 sola lesión pulmonar. La mediana de tamaño de la lesión fue de 20 mm y sólo 19.4 % presentaba metástasis extrapulmonares previo al procedimiento. La mediana de PFS fue de 10 meses (7.5-12.5). La mediana de supervivencia global post procedimiento fue de 24 meses (21.1-26.8). La supervivencia Global a 3 años fue 16%. La tasa de respuesta fue de 96.7%, respuesta completa en 53% y respuesta parcial en 43 %. Las complicaciones más frecuentes fueron dolor pleurítico, neumotórax y efusión pleural, ocurrió 1 arresto cardiaco y 1 muerte asociada al procedimiento. <br /><br />Conclusión: La ARF pulmonar demostró ser una terapia local que logra prolongar la supervivencia de nuestros pacientes con una tasa de eventos adversos aceptable y con complicaciones manejables.<br /><br />Abstract <br />Introduction: The evidence of surgical metastasectomy is small and without randomized studies. Short-term morbidity that may be responsible for permanent loss of time and with increased costs. Based on this, there is a need for local control therapies in patients who can not undergo metastasectomy. Methodology: we performed a retroactive review of all patients treated with pulmonary RFA between 2013 to 2018 in our institution. Demographic, clinical, therapeutic and prognostic variables were studied. The Kaplan-Meier method was used to analyze progression-free survival and overall survival. Results: 31 patients were analyzed, the median age was 63 years, 54.8% were female. The most frequent primary sites were Colon, breast and rectum. The majority with ECOG 1 and 1 single lung injury. The median size of the lesion was 20 mm and only 19.4% had extrapulmonary metastases at one year. The median PFS was 10 months (7.5-12.5). The median overall post-procedure survival was 24 months (21.1-26.8). Overall 3-year survival was 16%. The response rate was 96.7%, complete response 53% and partial response 43%. The most frequent complications were pleural pain, pneumothorax and pleural effusion, 1 cardiac arrest and 1 death associated with the procedure occurred.<br /><br />Conclusion: Pulmonary RFA proved to be a local therapy that managed to prolong the survival of our patients with an acceptable rate of adverse events and with manageable complications.</p>

Induction chemotherapy (IC) with EXTREME study regimen for locally advanced head and neck cancer (LAHNC) frail patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17564-e17564
Author(s):  
Valérie Cochin ◽  
Erwan De-Mones-Del-Pujol ◽  
Laurence Digue ◽  
Muriel Garcia-Ramirez ◽  
Charles Dupin ◽  
...  
Keyword(s):  
Retrospective Cohort ◽  
Median Overall Survival ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Feeding Tube ◽  
Complete Sequence ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Grade 3

e17564 Background: IC with TPF (docetaxel, cisplatin, 5FU) in LAHNC is limited to fit patients (pts). We conducted a retrospective cohort study to evaluate the use of EXTREME regimen (platinum, 5FU, cetuximab) as IC in LAHNC frail pts. Methods: Retrospective analysis of all consecutive pts with unresectable LAHNC treated with EXTREME regimen with or without 5FU as IC from two French centers from 2008 to 2015. We evaluated the rate of realization of the complete sequence (at least 2 cycles of IC and all radiation courses). Tolerance and efficacy, including clinical benefice, median progression free survival (PFS) and median overall survival (OS) were estimated. Results: We included 34 pts with average age of 56 years [46-70] (Table). Patients presented decreased weight (10% in one month or 15% in 6 months): 74% (n=25), pain: 76% (n=26), feeding tube: 82% (n=28), tracheotomy: 15% (n=4), fistula: 15% (n=4) and low albumin <35g/l: 41% (n=14), <25g/l: 12% (n=4). Six pts (17%) not received 5FU (cardiovascular history). Grade 3 toxicities were seen in 50% pts principally due to cisplatin. 5FU dose was decreased in 9% (n=3) and cisplatin switched to carboplatin in 15% (n=4). The sequence was achieved for 76% (n=26) of pts and 80% (n=27) presented clinical response with improvement of symptoms (increased weight: 32%, n=11). Six pts (17%) have a progression disease (PD) under IC, one patient (3%) died during bioradiotherapy (BRT) (stomach perforation) and one (3%) stopped IC after one cycle (infection) but achieved BRT. BRT with cetuximab was used in 85% (n=23) (average of 6 cycles [2-8]). PET-FDG at 3 months showed 9% (n=3) of complete response (CR) and 44% (n=15) of PD. Median PFS and OS were 5.7 and 15.5 months respectively. PD at 3 months was associated with decreased median OS: 21.9 versus 13.6 months, p=0.01. Conclusions: This is the first report of use of the EXTREME regimen as IC. This IC was used in a very frail population and the majority achieved sequence with significant clinical benefice. [Table: see text]

scholarly journals Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient® in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06)

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1223
Author(s):  
Daniel Pink ◽  
Dimosthenis Andreou ◽  
Sebastian Bauer ◽  
Thomas Brodowicz ◽  
Bernd Kasper ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Phase Ii Trial ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Future Studies ◽  
Entire Cohort

We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7–15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, p = 0.0247) and PFS (11.3 vs. 2.7 months, p < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.

scholarly journals Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  
Keyword(s):  
Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Node Metastases ◽  
Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

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