Nivolumab demonstrates benefit over nomogram-predicted 12-month survival as salvage therapy for metastatic urothelial carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 451-451 ◽  
Author(s):  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Matt D. Galsky ◽  
Padmanee Sharma ◽  
Jonathan E. Rosenberg ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Urothelial Carcinoma ◽  
Salvage Therapy ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Statistical Significance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Metastatic Urothelial Carcinoma

451 Background: Intermediate endpoints of benefit in metastatic urothelial carcinoma (mUC) nonrandomized trials are necessary to identify promising drugs, particularly for checkpoint inhibitors, where response and progression-free survival remain suboptimal. We previously reported a nomogram (Pond GR et al, 2017 GU Cancers Symposium) using 5 prognostic factors (hemoglobin < 10 g/dL, Eastern Cooperative Oncology Group performance status ≥1, presence of liver metastasis, time from last treatment ≤3 months, and albumin < lower limit of normal) from phase 2 trials of historical agents (eg, taxanes) to estimate 12-month overall survival (OS), against which observed survival could be compared. Nivolumab was granted approval as salvage therapy for patients with mUC, based on the CheckMate (CM) 275 trial; it is thus of interest to compare the nivolumab observed survival versus nomogram-predicted survival results. Methods: Data were obtained from CM 275, including survival and all 5 prognostic factors. Nomogram points were calculated and the expected 12-month OS was estimated. Bootstrap analyses based on 2000 replications were used to estimate 95% confidence intervals (CIs) for the median expected, observed, and difference between the expected and observed 12-month OS values. All tests were 2-sided, with statistical significance defined as P≤0.05. Results: Data were available from 270 patients from CM 275. Fifteen patients did not have albumin recorded and were excluded. Among the 255 evaluable patients, 46 (18.0%) patients had 0 adverse prognostic factors, 85 (33.3%) had 1, and 124 (48.6%) had 2 or more. The observed nivolumab 12-month OS from CM 275 (43.3% [95% CI, 37.0%-50.5%]) was 19.8% higher (95% CI, 13.6%-26.4%) when compared with the nomogram-predicted 12-month OS (23.5%; [95% CI, 22.5%-25.5%]) if patients received historical chemotherapy. Across all 2000 bootstrap samples, the observed nivolumab 12-month OS exceeded the nomogram-predicted 12-month OS. Conclusions: Nivolumab was associated with a significantly improved 12-month OS compared with historical chemotherapy based on the value predicted by the validated nomogram incorporating baseline prognostic factors. Clinical trial information: NCT02387996.

Nomogram to assess survival benefit of new over historical agents as salvage therapy for metastatic urothelial carcinoma (mUC) in non-randomized trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16012-e16012
Author(s):  
Guru Sonpavde ◽  
Gregory Russell Pond ◽  
Jonathan E. Rosenberg ◽  
Toni K. Choueiri ◽  
Joaquim Bellmunt ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Salvage Therapy ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Free Survival ◽  
Phase Ii Studies ◽  
Metastatic Urothelial Carcinoma ◽  
The Impact

e16012 Background: Surrogate endpoints of benefit in mUC phase 2 salvage therapy trials are necessary to identify promising drugs, particularly for checkpoint inhibitors where response and progression-free survival are inadequate. We developed a nomogram using prognostic variables from phase 2 trials of historical agents to estimate 12 month survival to which observed survival in phase 2 trials could be compared. Methods: Data were obtained from phase 2 trials of salvage therapy for mUC for survival and 5 prognostic factors: hemoglobin, performance status, liver metastasis, treatment-free interval and albumin. Patients (pts) were randomly allotted to discovery:validation (DIS:VAL) datasets in a 2:1 ratio. A nomogram was developed for estimating 12-month survival. Calibration plots were constructed in the VAL dataset by plotting estimated vs. observed 12-mo survival and data bootstrapped to assess performance. The nomogram was applied to external nonrandomized salvage therapy data: 1) retrospective pemetrexed data or 2) trials of atezolizumab: PCD4989g and IMvigor210. Results: Data were available from 340 pts receiving sunitinib (n = 77), everolimus (n = 45), docetaxel + vandetanib or placebo (n = 109), pazopanib (n = 42), paclitaxel (n = 36) and docetaxel (n = 31). Calibration and prognostic ability of the model was acceptable (c-index = 0.634, 95% CI = 0.596-0.652). Observed 12-month survival for pts on pemetrexed (n = 127, 23.5% [95% CI: 16.2%-31.7%]) were similar to nomogram-predicted survival (19% [95% CI: 16.5-21.5], P> 0.05), while observed result with atezolizumab (n = 403, 39.0% [95% CI: 34.1-43.9]) exceeded predicted result (24.6% [95% CI: 23.4-25.8], P< 0.001). Conclusions: Atezolizumab was associated with a significantly longer 12-mo survival compared to nomogram-predicted survival while pemetrexed was not. This nomogram incorporates baseline prognostic factors to provide expected 12-mo survival of phase 2 patient cohorts with which to compare observed survival, providing a useful tool to quantify benefit in phase II studies while controlling the impact of clinical variables.

scholarly journals Pembrolizumab for patients with leptomeningeal metastasis from solid tumors: efficacy, safety, and cerebrospinal fluid biomarkers

2021 ◽  
Vol 9 (8) ◽  
pp. e002473
Author(s):  
Jarushka Naidoo ◽  
Karisa C Schreck ◽  
Wei Fu ◽  
Chen Hu ◽  
Alexander Carvajal-Gonzalez ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Solid Tumors ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Squamous Carcinoma ◽  
Leptomeningeal Metastasis ◽  
Progression Free Survival ◽  
Cytokine Analysis

BackgroundThe benefit of immune checkpoint inhibitors (ICIs) in patients with leptomeningeal metastases (LMM) is unknown.MethodsWe undertook a phase II trial of pembrolizumab in patients with LMM from solid tumors. Eligible patients had radiologic/cytologic LMM and Eastern Cooperative Oncology Group performance status 0–1. Pembrolizumab was administered intravenously at 200 mg q3W until disease progression/unacceptable toxicity. The primary endpoint was central nervous system (CNS) response after four cycles, defined radiologically/cytologically/clinically. Serial cerebrospinal fluid (CSF) was assessed for tumor-derived DNA (t-DNA) aneuploidy and cytokines.ResultsThirteen of a planned 16 patients were treated between April 2017 and December 2019. The study closed early for poor accrual. Median age was 57 years (range: 22–79). Sixty-two percent of patients had tumors not traditionally ICI-responsive (hormone-receptor (HR)-positive breast carcinoma=39%; high-grade glioma=23%), while 38% had ICI-responsive tumors (non-small cell lung cancer (NSCLC)=23%, head and neck carcinoma=8%, cutaneous squamous carcinoma (CSC)=8%). CNS response was observed in 38% of patients at 12 weeks (95% CI 13.9% to 68.4%) by pre-defined criteria and LM-RANO, and 2 achieved durable complete responses (CSC=1, overall survival (OS) 3+ years; NSCLC=1, OS 9 months). Median CNS progression-free survival and OS was 2.9 months (95% CI 1.3 to NR) and 4.9 months (95% CI 3.7 to NR), respectively. Grade 3+ treatment-related adverse events occurred in 15% of patients. Sensitivity for LMM detection by t-DNA and cytopathology was 84.6% (95% CI 54.6% to 98.1%) and 53.9% (95% CI 25.1% to 80.8%), respectively. Pre-therapy and on-therapy CSF cytokine analysis demonstrated complete responders clustered together.ConclusionsPembrolizumab conferred a 38% CNS response rate in patients with LMM, a tolerable safety profile, and deep responses in selected patients with ICI-responsive tumors. CSF t-DNA may be sensitive for LMM detection, and immunologic subsets of CNS response warrant further study.Trial registration numberNCT03091478

Nomogram to assess benefit of new over historical agents as salvage therapy for metastatic urothelial carcinoma (mUC) in non-randomized trials: Effect of atezolizumab on 12-month survival.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 346-346 ◽  
Author(s):  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Jonathan E. Rosenberg ◽  
Toni K. Choueiri ◽  
Joaquim Bellmunt ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Phase Ii ◽  
Salvage Therapy ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Phase Ii Trials ◽  
Phase Ii Studies ◽  
The Impact

346 Background: Early surrogate endpoints of benefit in mUC phase 2 salvage therapy trials are necessary to identify promising drugs, particularly for checkpoint inhibitors where response and progression-free survival are inadequate. We developed a nomogram using prognostic variables from phase 2 trials of historical agents to estimate 12 month survival to which observed survival in single arm trials could be compared. Methods: Data were obtained from phase II trials of salvage therapy for mUC for survival and 5 prognostic factors: hemoglobin, performance status, liver metastasis, treatment-free interval and albumin. Patients (pts) were randomly allotted to discovery:validation (DIS:VAL) datasets in a 2:1 ratio. A nomogram was developed for estimating 12-month survival. Calibration plots were constructed in the VAL dataset by plotting estimated vs. observed 12-mo survival and data bootstrapped to assess performance. The nomogram was applied to external nonrandomized salvage therapy data: 1) retrospective pemetrexed data or 2) trials of atezolizumab: PCD4989g and IMvigor210. Results: Data were available from 340 pts receiving sunitinib (n = 77), everolimus (n = 45), docetaxel + vandetanib or placebo (n = 109), pazopanib (n = 42), paclitaxel (n = 36) and docetaxel (n = 31). Calibration and prognostic ability of the model was acceptable (c-index = 0.634, 95% CI = 0.596-0.652). Observed 12-month survival for pts on pemetrexed (n = 127, 23.5% [95% CI: 16.2%-31.7%]) were similar to nomogram-predicted survival (19% [95% CI: 16.5-21.5], P> 0.05), while observed result with atezolizumab (n = 403, 39.0% [95% CI: 34.1-43.9]) exceeded predicted result (24.6% [95% CI: 23.4-25.8], P< 0.001). Conclusions: Atezolizumab was associated with a significantly longer 12-mo survival compared to nomogram-predicted survival while pemetrexed was not. This nomogram incorporates baseline prognostic factors to provide expected 12-mo survival of phase 2 patient cohorts with which to compare observed survival, thereby providing a useful tool to quantify benefit in phase II studies while controlling for the impact of clinical variables.

scholarly journals Effectiveness and Safety of Immune Checkpoint Inhibitors for Patients with Advanced Non Small-Cell Lung Cancer in Real-World: Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1388
Author(s):  
Manlio Mencoboni ◽  
Marcello Ceppi ◽  
Marco Bruzzone ◽  
Paola Taveggia ◽  
Alessia Cavo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Small Cell Lung ◽  
Eligibility Criteria

Immunotherapy based on anti PD-1/PD-L1 inhibitors is the new standard of advanced non-small cell lung cancers. Pembrolizumab, nivolumab and atezolizumab are used in clinical practice. The strict eligibility criteria of clinical trials do not allow researchers to fully represent treatment effects in the patients that will ultimately use these drugs. We performed a systematic review and a meta-analysis to evaluate the effectiveness and safety of these drugs, and more generally of ICIs, as second-line therapy in NSCLC patients in real world practice. MEDLINE, PubMed, Scopus and Web of Science were searched to include original studies published between January 2015 and April 2020. A total of 32 studies was included in the meta-analysis. The overall radiological response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and overall survival (OS) were 21%, 52%, 3.35 months and 9.98 months, respectively. The results did not change when analysis was adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) and age. A unitary increase in the percent of patients with liver and CNS metastases reduced the occurrence of DCR by 7% (p < 0.001) and the median PFS by 2% (p = 0.010), respectively. The meta-analysis showed that the efficacy and safety of immunotherapy in everyday practice is comparable to that in clinical trials.

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

2009 ◽  
Vol 27 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Melanie B. Thomas ◽  
Jeffrey S. Morris ◽  
Romil Chadha ◽  
Michiko Iwasaki ◽  
Harmeet Kaur ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Study Objective ◽  
Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

scholarly journals Phase Ib/II trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4) combined with FOLFOX in patients with metastatic colorectal cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. e000375 ◽  
Author(s):  
Jean-David Fumet ◽  
Nicolas Isambert ◽  
Alice Hervieu ◽  
Sylvie Zanetta ◽  
Jean-Florian Guion ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Target Therapy ◽  
Performance Status ◽  
Human Monoclonal Antibody ◽  
Eastern Cooperative Oncology Group ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Mutational Status

Background5-Fluorouracil plus irinotecan or oxaliplatin alone or in association with target therapy are standard first-line therapy for metastatic colorectal cancer (mCRC). Checkpoint inhibitors targeting PD-1/PD-L1 demonstrated efficacy on mCRC with microsatellite instability but remain ineffective alone in microsatellite stable tumour. 5-Fluorouracil and oxaliplatin were known to present immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate whether the addition of PD-L1 and CTLA-4 inhibition to oxaliplatin, fluorouracil and leucovorin (FOLFOX) increases treatment efficacy.MethodsThis phase II study (ClinicalTrials.gov NCT03202758) will assess the efficacy and safety of FOLFOX/D/T association in patients with mCRC (n=48). Good performance status patients (Eastern Cooperative Oncology Group <2) with untreated, RAS mutational status mCRC will be eligible. Prior adjuvant therapy is allowed provided recurrence is >6 months postcompletion. There is a safety lead in nine patients receiving FOLFOX/D/T. Assuming no safety concerns the study will go on to include 39 additional patients. Patients will receive folinic acid (400 mg/m²)/5-fluorouracil (400 mg/m² as bolus followed by 2400 mg/m2 as a 46-hour infusion)/oxaliplatin (85 mg/m2) every 14 days with D (750 mg) D1 every 14 days and T (75 mg) D1 every 28 days. After six cycles of FOLFOX only D/T will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is safety and efficacy according to progression-free survival (PFS); secondary endpoints include overall response rate and quality of life. Hypothesis is that a PFS of 50% at 6 months is insufficient and a PFS of 70.7% is expected (with α=10%, β=10%). Blood, plasma and tumour tissue will be collected and assessed for potential prognostic and predictive biomarkers.

Treatment patterns among patients with advanced urothelial carcinoma following discontinuation of PD1/L1 inhibitor therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 414-414
Author(s):  
Alicia K. Morgans ◽  
Simrun Kaur Grewal ◽  
Zsolt Hepp ◽  
Rupali Fuldeore ◽  
Shardul Odak ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Real World ◽  
Chart Review ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Unmet Need ◽  
Case Series ◽  
Treatment Patterns

414 Background: There are a lack of published real-world data on treatment patterns for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) previously treated with programmed death 1/ligand 1 inhibitor (PD-1/L1i) therapy. The objective of this study was to characterize the clinical characteristics and treatments among patients with la/mUC following discontinuation of first-line (1L) or second-line (2L) PD-1/L1i therapy. Methods: We performed a retrospective chart review at 26 geographically diverse clinical sites in the US. Patients aged ≥18 years with histologically or cytologically confirmed urothelial carcinoma and radiographic evidence of metastatic or locally advanced disease were identified. Included patients had initiated and subsequently discontinued PD-1/L1i therapy in the 1L or 2L setting for la/mUC between May 15, 2016-July 31, 2018. All patients had follow-up through October 31, 2019. Data were summarized using descriptive statistics. Results: Among the 300 patients included in the chart review, 198 (66%) received PD-1/L1i therapy as 1L and 102 (34%) as 2L therapy. Mean (SD) age at la/mUC diagnosis was 69.4 (8.7) years, and a majority of patients were male (66.0%) and White (74.7%). Consistent with age, most patients (82.7%) had comorbidities at la/mUC diagnosis; 39.7% hypertension, 23.7% coronary artery disease, 17.7% pulmonary disease, and 9.3% renal disease. At initiation of therapy, a higher proportion of patients who received 1L PD-1/L1i therapy had an Eastern Cooperative Oncology Group performance status of 2 or more than patients who received 2L PD-1/L1i therapy (36.8% vs 22.5%, respectively). Following discontinuation of PD-1/L1i therapy, 34% (n = 68) received subsequent therapy in 2L and 29% (n = 30) in third-line (3L). The most common subsequent therapies in 2L were gemcitabine monotherapy (24%), gemcitabine plus cisplatin or carboplatin (22%), PD-1/L1i therapy (22%), and taxane monotherapy (19%). The most common subsequent therapies received in 3L were taxane monotherapy (50%), pemetrexed (17%), and PD-1/L1i therapy (16%). Overall, switching from one PD-1/L1i therapy to another distinct PD-1/L1i therapy occurred in approximately 20% of patients, with “better efficacy/survival” noted by treatment teams as the most common reason for switching therapy among this subgroup. Conclusions: In this real-world case series, only a minority of patients with la/mUC who discontinued PD-1/L1i therapy received subsequent therapy. Among those that did, no clear standard of care was observed and approximately one-fifth of patients were treated with a second PD-1/L1i therapy after the first failed to control disease. Collectively, the data highlight significant unmet need for patients with la/mUC who discontinue PD-1/L1i therapy.

Immunotherapy and Sonpavde score validation in advanced upper tract urothelial carcinoma: a retrospective study by the Italian Network for Research in Urologic-Oncology

Immunotherapy ◽  
2021 ◽  
Author(s):  
Melissa Bersanelli ◽  
Giulia Mazzaschi ◽  
Patrizia Giannatempo ◽  
Daniele Raggi ◽  
Elena Farè ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Upper Tract Urothelial Carcinoma ◽  
Urologic Oncology ◽  
Upper Tract ◽  
Treatment Decision Making ◽  
Few Data

Background: Few data are available regarding the effectiveness of immune checkpoint inhibitors in advanced upper tract urothelial carcinoma (UTUC) patients. Methods: To provide a real-world experience with anti-PD-1/PD-L1-based therapy in UTUC patients, we involved an Italian network in a multicenter retrospective analysis. Results: A total of 78 UTUC patients were enrolled. The median follow-up was 25.1 months. The median progression-free survival (mPFS) was 2.2 months (95% CI 1.8–2.6), and the median OS (mOS) was 6.0 months (95% CI 3.6–8.4). The Sonpavde score (including performance status > 0, hemoglobin < 10 g/dl, liver metastases, time from prior chemotherapy ≥ 3 months) split the patients into three groups (0 vs 1 vs 2–4 factors), efficiently predicting the OS and PFS outcome at the multivariate analyses (p < 0.0001). Conclusion: The prognosis of unselected UTUC patients is still unsatisfactory. The Sonpavde score was validated for the first time in an UTUC population, as a useful tool for the treatment decision-making process.

Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine

2017 ◽  
Vol 35 (30) ◽  
pp. 3433-3439 ◽  
Author(s):  
George D. Demetri ◽  
Patrick Schöffski ◽  
Giovanni Grignani ◽  
Jean-Yves Blay ◽  
Robert G. Maki ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Eribulin Mesylate ◽  
Systemic Treatments ◽  
Phase Iii Study

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.

Low Geriatric Nutritional Risk Index as a Poor Prognostic Marker for Second-Line Pembrolizumab Treatment in Patients with Metastatic Urothelial Carcinoma: A Retrospective Multicenter Analysis

Oncology ◽  
2020 ◽  
Vol 98 (12) ◽  
pp. 876-883
Author(s):  
Toshiki Etani ◽  
Taku Naiki ◽  
Yosuke Sugiyama ◽  
Takashi Nagai ◽  
Keitaro Iida ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Urothelial Carcinoma ◽  
Group Performance ◽  
Risk Index ◽  
Nutritional Risk ◽  
Second Line ◽  
Geriatric Nutritional Risk Index ◽  
Platinum Based Chemotherapy ◽  
Nutritional Risk Index ◽  
Metastatic Urothelial Carcinoma

<b><i>Background:</i></b> We evaluated the prognostic efficacy of the Geriatric Nutritional Risk Index (GNRI) in second-line pembrolizumab (PEM) therapy for patients with metastatic urothelial carcinoma (mUC). <b><i>Patients and Methods:</i></b> From January 2018 to October 2019, 52 mUC patients, treated previously with platinum-based chemotherapy, underwent second-line PEM therapy. Peripheral blood parameters were measured at the start of treatment: serum neutrophil-to-lymphocyte ratio (NLR), serum albumin, serum C-reactive protein (CRP), and body height and weight. PEM was intravenously administered (200 mg every 3 weeks). The patients were organized into two groups based on their GNRI (&#x3c;92 [low GNRI] and ≥92 [high GNRI]), and the data were retrospectively analyzed. Adverse events (AEs) were evaluated and imaging studies assessed for all patients. Analyses of survival and recurrence were performed using Kaplan-Meier curves. Potential prognostic factors affecting cancer-specific survival (CSS) were assessed by univariate and multivariate Cox regression analyses. <b><i>Results:</i></b> patients’ baseline characteristics, except for their BMI and objective response rate, did not significantly differ between the two groups. The median total number of cycles of PEM therapy was significantly higher for the high-GNRI group (<i>n</i> [range]: 6 [2–20] vs. 3 [1–6]). The median CSS with second-line PEM therapy was 3.6 months (95% confidence interval [CI]: 2.5–6.1) and 11.8 months (95% CI: 6.2–NA) in the low-GNRI and the high-GNRI group (<i>p</i> &#x3c; 0.01), respectively. Significant differences in CSS between the low- and high-CRP or -NRL groups were not found. Multivariate Cox proportional-hazards regression analysis revealed that a poor Eastern Cooperative Oncology Group performance status, visceral metastasis, and a low GNRI were significant prognostic factors for short CSS (95% CI: 1.62–6.10, HR: 3.14; 95% CI: 1.13–8.11, HR: 3.03; 95% CI: 1.32–8.02, HR: 3.25, respectively). Of the AEs, fatigue showed a significantly higher incidence in the low-GNRI group. <b><i>Conclusions:</i></b> For mUC patients receiving second-line PEM therapy, the GNRI is a useful predictive biomarker for survival outcome.

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