A prospective, randomized, open-label, phase III clinical trial of NovoTTF-100A versus best standard of care chemotherapy in patients with recurrent glioblastoma.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA2007-LBA2007 ◽  
Author(s):  
R. Stupp ◽  
A. Kanner ◽  
H. Engelhard ◽  
V. Heidecke ◽  
S. Taillibert ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Treatment Failure ◽  
Treatment Modality ◽  
The United States ◽  
Phase Iii ◽  
Time To Treatment ◽  
Novel Treatment ◽  
Long Term Treatment ◽  
Time To Treatment Failure

LBA2007 Background: The NovoTTF is a portable, medical device delivering low intensity, intermediate frequency, alternating electric fields by means of noninvasive, disposable scalp electrodes. These tumor treatment fields (TTF) physically interfere with cell division and assembly of organelles. Methods: Adult pts (KPS≥70%) with recurrent GBM were randomized (stratified by surgery for recurrence and center) to either NovoTTF administered continuously (20-24h/day, 7 days/week) or the best standard chemotherapy (BSC) at each physicians’ discretion. Number of prior therapies was not limited. Primary endpoint was overall survival (OS). The study was powered (80%) to detect a 60% increase in OS with a two tailed a of 0.05. Results: 237 pts were randomized (28 centers in the United States and Europe) to either TTF alone (120 pts) or BSC (117 pts). Patient characteristics were balanced, median age was 54 years (range 23-80), median KPS 80% (50-100). All had prior TMZ/RT, and the majority at least one prior therapy for recurrence. One-quarter had surgery for recurrence. Mean treatment duration was 4.4 mo (0-40) vs. 2.3 mo (0-15), median OS was 6.6 vs. 6.0 months for TTF and BSC, respectively (p=0.23, hazard ratio 0.84 [95% CI 0.63-1.12]), the 1-year survival rate 23.6% versus 20.8% (ns). PFS6 was 17.6% in both groups. Time to treatment failure favored the TTF group (HR 0.76 [0.57-1.02], p=0.07). Objective responses were more common in the TTF arm (12%) versus the BSC (6%). Related adverse events were mild-to-moderate skin rash beneath the electrodes in 17% of TTF treated pts. Hematological and other toxicities were observed at a significantly higher incidence in the BSC arm depending on the type of chemotherapy, no treatment-related deaths occurred. Treatment compliance with TTF was excellent with a median duration 20 hours/day. Conclusions: This is the first phase III, controlled clinical trial testing TTF, an entirely novel treatment modality. TTF had minimal toxicity, long-term treatment proved feasible. TTF as a single modality showed a higher response rate and longer time to treatment failure compared to best available chemotherapy. Overall survival also favored TTF, but did not reach statistical significance. In view of the above, TTF should be considered a valid novel treatment modality. [Table: see text]

Front - Line Combined Immuno-Chemotherapy (R-CHOP) Significantly Improves the Time to Treatment Failure and Overall Survival in Elderly Patients with Advanced Stage Follicular Lymphoma - Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 482-482 ◽  
Author(s):  
Christian Buske ◽  
Michael Kneba ◽  
Eva Lengfelder ◽  
Michael Pfreundschuh ◽  
Wolf-Dieter Ludwig ◽  
...  
Keyword(s):  
Overall Survival ◽  
Side Effects ◽  
Elderly Patients ◽  
Treatment Failure ◽  
Follicular Lymphoma ◽  
Phase Iii ◽  
Advanced Stage ◽  
Logrank Test ◽  
Time To Treatment ◽  
Time To Treatment Failure

Abstract Follicular lymphoma (FL) is an indolent disease of the advanced age with more than 40 % of the patients being older than 60 years at diagnosis and an age-specific incidence peaking above 75 years. We now analyzed the treatment outcome of elderly patients in the GLSG multicenter phase III study comprising a prospective randomized comparison of R-CHOP versus CHOP alone in patients with advanced stage FL. 221 patients > 60 years with untreated FL were randomized for therapy with R-CHOP (R-CHOP: Rituximab 375 mg/m2 d0–1; cyclophosphamide 750 mg/m2 d1; doxorubicine 50 mg/m2 d1; vincristine 1.4 mg/m2 d1; prednisone 100 mg/m2 d1–5) (n=109) or CHOP alone (n=112). Patient characteristics were well balanced between the treatment groups, also with regard to the distribution of the FLIPI risk groups (≥ 3 adverse factors 73% and 66 % in the R-CHOP and CHOP arm, respectively). R-CHOP induced higher overall response rates and significantly prolonged the time to treatment failure (TTF)(median 5.0 years versus 2.1 years, respectively; logrank test: p<0.0001) compared to CHOP in the elderly patient group. Furthermore, the estimated 4-years progression free survival was 62.2% for R-CHOP versus 27.9 % after CHOP (logrank: p< 0.0001). Importantly, R-CHOP was able to prolong the overall survival in elderly patients compared to CHOP with an estimated 4-years overall survival of 90% after immunochemotherapy versus 81 % after CHOP alone (logrank test: p=0.039). In the multivariate analysis individual FLIPI risk factors such as elevated serum LDH level, a hemoglobin level below 12 g/dl, the number of nodal areas (> 4) as well as application of CHOP alone were independently associated with a shorter TTF. Treatment related side effects were similar in both patient groups and comprised predominantly myelosuppression. In summary, the addition of Rituximab to CHOP significantly improves the outcome of elderly patients with previously untreated advanced stage FL without adding major side effects.

SPEAR-Bladder (Study informing treatment Pathway dEcision in bladder cAnceR): Influence of treatment sequencing on time to treatment failure and overall survival in the United States.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 453-453
Author(s):  
Gurjyot K. Doshi ◽  
Mairead Kearney ◽  
Murtuza Bharmal ◽  
Hemant Phatak ◽  
Marley Boyd ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Disease Status ◽  
The United States ◽  
Future Research ◽  
Time To Treatment ◽  
Kaplan Meier ◽  
Time To Treatment Failure

453 Background: With the introduction of immunotherapy (IO) for locally advanced or metastatic urothelial carcinoma (mUC), optimal treatment sequence should be considered. This study aimed to compare time to treatment failure (TTF) and overall survival (OS) among these patients (pts) treated with first-line (1L) systemic chemotherapy followed by second-line (2L) IO ( C-IO) vs 1L and 2L chemotherapy ( C-C) sequence within the US community oncology Network (USON). Methods: This was a retrospective study of adult locally advanced or mUC pts who initiated systemic therapy between 1/1/15 – 4/30/17 within USON and had a minimum of two-month follow-up. Descriptive analyses were performed, with Kaplan-Meier used for comparisons between pts who received C-IO vs C-C sequence. Pts considered for this analysis did not receive a third-line treatment. Regression analyses were performed to assess variables associated with TTF and OS. Results: 117 pts were included in the analysis ( C-IO n = 79, C-C n = 38). Median age (range) was 69 years (38, 90+), with 74.4% male. Baseline demographic and clinical characteristics were similar between the groups. The median (range) duration between start of 1L and start of 2L therapy was significantly longer among C-IO vs C-C pts (29.0 [4.1, 102.1] vs 20.0 [0.1, 63.1] weeks; P = 0.0047). Median TTF and OS were longer among C-IO vs C-C pts but the trends were not significant (Table). The duration between initial diagnosis and advanced disease status was associated with TTF (P = 0.0124) in univariate analysis. Conclusions: These results suggest that patients receiving C-IO demonstrated greater (>30 weeks) but statistically non-significant improvement in OS versus those receiving C-C. Considering these OS trends, future research should explore prognostic characteristics of IL chemotherapy treated pts who may benefit from an earlier switch to IO therapy. [Table: see text]

scholarly journals Phase III Study Comparing Gemcitabine Plus Cetuximab Versus Gemcitabine in Patients With Advanced Pancreatic Adenocarcinoma: Southwest Oncology Group–Directed Intergroup Trial S0205

2010 ◽  
Vol 28 (22) ◽  
pp. 3605-3610 ◽  
Author(s):  
Philip A. Philip ◽  
Jacqueline Benedetti ◽  
Christopher L. Corless ◽  
Ralph Wong ◽  
Eileen M. O'Reilly ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Treatment Failure ◽  
Survival Time ◽  
Pancreatic Adenocarcinoma ◽  
Pancreas Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Time To Treatment ◽  
Time To Treatment Failure

Purpose Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor. Patients and Methods Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity. Results A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset. Conclusion In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.

The Addition of Rituximab to First-Line Chemotherapy (R-CHOP) Results in Superior Response Rates, Time to Treatment Failure and Response Duration in Patients with Advanced Stage Mantle Cell Lymphoma: Long Term Results of a Randomized GLSG Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3049-3049 ◽  
Author(s):  
Eva Hoster ◽  
Michael Unterhalt ◽  
Bernhard Wörmann ◽  
Ulrich Dührsen ◽  
Bernd Metzner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Cell Lymphoma ◽  
Response Duration ◽  
Response Rates ◽  
Time To Treatment ◽  
Mantle Cell ◽  
Time To Treatment Failure

Abstract Background: The addition of rituximab to chemotherapy (R-CHOP) has been shown to improve response rates in mantle cell lymphoma (MCL), but prolongation of response duration or overall survival was not observed (Lenz et al., JCO 2005). In a similar randomized comparison of 90 patients, again the addition of rituximab to MCP showed a tendency towards higher CR rates, but no improvement of overall response rate, progression free, or overall survival (Herold et al., ICML-10, 2008). Methods: We present an update of a previously published trial randomly comparing efficacy and safety of R-CHOP to CHOP induction in previously untreated patients with advanced stage MCL. Results: Of the 123 evaluable patients, 63 patients were randomized to R-CHOP. Median age was 62 years, and risk profiles of the two treatment arms were comparable. Overall response rates were 92% vs. 75% for R-CHOP vs. CHOP (p = 0.0139) and complete remission rates 33% vs. 8% (p = 0.0008). After a median follow-up of 65 months, median time to treatment failure was prolonged from 14 months for CHOP to 28 months for R-CHOP (p = 0.0003). Similarly, median response duration was prolonged from 18 (CHOP) to 29 months (R-CHOP, p = 0.0052). So far, no significant improvement of overall survival has been observed with median not reached vs. 59 months and 5-years OS rates of 59% and 46% (p = 0.27) after R-CHOP and CHOP, respectively. Toxicity was not significantly higher for R-CHOP treated patients. Conclusions: After longer follow-up, superior remission rates, time to treatment failure, and response duration of combined immuno-chemotherapy were confirmed. However, in contrast to other lymphoma entities, improvement of overall survival has not yet been proven in MCL patients. Therefore new therapeutic options are urgently warranted to further improve the long term outcome in this otherwise dismal disease.

A multicenter phase II study of pemetrexed and cisplatin in patients with advanced gastric cancer (AGC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14008-14008
Author(s):  
Y. Bang ◽  
Y. Kim ◽  
H. C. Chung ◽  
W. Kang ◽  
S. Park ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Median Time ◽  
Progressive Disease ◽  
Treatment Schedule ◽  
Curative Surgery ◽  
Time To Treatment ◽  
Time To Treatment Failure ◽  
Common Grade ◽  
Grade 3

14008 Background: Pemetrexed is a novel folate antimetabolite, and it inhibits a number of folate-dependent enzymes. This agent has demonstrated activity in a variety of tumor types including AGC. This study was performed to evaluate the combination of pemetrexed and cisplatin in the treatment of AGC. The primary endpoint was response rate, and secondary endpoints were duration of response, time to progressive disease, time to treatment failure, overall survival, and toxicity. Methods: Patients with stage IV AGC not to be amendable to curative surgery and measurable disease were eligible. Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 were given on day 1, every 21 days. Treatment was supplemented with folic acid, vitamin B12, and dexamethasone. Response was assessed by RECIST, and toxicity was assessed by NCI-CTC v 2.0. Results: From October 2003 to September 2004, 51 patients were enrolled, but 1 did not meet the eligibility criteria. There were 37 men and 13 women with a median age of 56 years (range, 24–69) and an ECOG PS 0/1 for 14/36 patients; all had metastatic disease. Of 50 evaluable patients, there were no complete responses, and 13 had confirmed partial responses (26%; 95% CI, 14.6%-40.3%). Fifteen patients (30%) had stable disease, and 21 (42%) progressed, and 1 (2%) was unknown. Among 13 responders, the median durarion of response was 3.60 months (95% CI, 2.80–9.40). Median time to progressive disease was 2.8 months (95% CI, 2.20–4.40), and median overall survival was 6.6 months (95% CI, 4.80–10.40). The median time to treatment failure was 2.10 months (95% CI, 1.00–2.80). Survival estimates were 32.0% at 3 months and 7.0% at 6 months. A total of 212 cycles were administered to 51 patients (median 4 [range, 1–13]). Based on 51 patients, most common grade 3/4 hematologic toxicities were neutropenia (49.0%), leukopenia (19.7%), and anemia (13.7%); the most common grade 3/4 nonhematologic toxicities were hyponatremia (15.7%), anorexia (9.8%), nausea (7.8%), and vomiting (7.8%). Conclusions: : The combination of pemetrexed and cisplatin in the current dose and schedule has a modest activity and a mild toxicity profile in patients with AGC. Further study is warranted using a different dose and treatment schedule. [Table: see text]

scholarly journals CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers

2016 ◽  
Vol 34 (23) ◽  
pp. 2736-2742 ◽  
Author(s):  
Peter C. Enzinger ◽  
Barbara Ann Burtness ◽  
Donna Niedzwiecki ◽  
Xing Ye ◽  
Kathe Douglas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Response Rate ◽  
Gastroesophageal Junction ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Free Survival ◽  
Time To Treatment ◽  
Time To Treatment Failure ◽  
One To One

Purpose To determine the optimal chemotherapy backbone for testing in future US cooperative group studies for metastatic esophageal and gastroesophageal junction cancers. Cetuximab was added to each treatment arm based on promising preclinical data. Patients and Methods Patients with previously untreated metastatic esophageal or gastroesophageal junction cancer were randomly assigned at a one-to-one-to-one ratio to epirubicin, cisplatin, and continuous-infusion fluorouracil (ECF), irinotecan plus cisplatin (IC), or FOLFOX (oxaliplatin, leucovorin, and bolus and infusional fluorouracil). All treatment programs included cetuximab once per week. The primary end point was response rate. Secondary outcomes included overall survival, progression-free survival, time to treatment failure, and safety. As prespecified, primary and secondary analyses were conducted only among patients with adenocarcinoma. Results This study randomly assigned 245 patients, including 222 with adenocarcinoma. Among patients with adenocarcinoma, response rate was 60.9% (95% CI, 47.9 to 72.8) for ECF plus cetuximab, 45.0% (95% CI, 33.0 to 57.0) for IC plus cetuximab, and 54.3% (95% CI, 42.0 to 66.2) for FOLFOX plus cetuximab. Median overall survival was 11.6, 8.6, and 11.8 months; median progression-free survival was 7.1, 4.9, and 6.8 months; and median time to treatment failure was 5.6, 4.3, and 6.7 months for each of these arms, respectively. FOLFOX plus cetuximab required fewer treatment modifications compared with ECF plus cetuximab and IC plus cetuximab (P = .013), and fewer patients were removed from treatment because of an adverse event or experienced treatment-related death. Conclusion In combination with cetuximab, ECF and FOLFOX had similar efficacy, but FOLFOX was better tolerated. Although differences were nonsignificant, IC plus cetuximab seemed to be the least effective and most toxic of the three regimens tested.

scholarly journals Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center

2015 ◽  
Vol 33 (28) ◽  
pp. 3193-3198 ◽  
Author(s):  
Troy Z. Horvat ◽  
Nelly G. Adel ◽  
Thu-Oanh Dang ◽  
Parisa Momtaz ◽  
Michael A. Postow ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Treatment Failure ◽  
Systemic Corticosteroid ◽  
Standard Dose ◽  
Corticosteroid Treatment ◽  
Cancer Center ◽  
Time To Treatment ◽  
Systemic Corticosteroids ◽  
Time To Treatment Failure

Purpose Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab treatment outside of clinical trials to determine the frequency of use of systemic corticosteroid or anti-tumor necrosis factor α (anti-TNFα) therapy and the effect of these therapies on overall survival (OS) and time to treatment failure (TTF). Patients and Methods We reviewed retrospectively the medical records of patients with melanoma who had received treatment between April 2011 and July 2013 with ipilimumab at the standard dose of 3 mg/kg. We collected data on patient demographics, previous and subsequent treatments, number of ipilimumab doses, irAEs and how they were treated, and overall survival. Results Of the 298 patients, 254 (85%) experienced an irAE of any grade. Fifty-six patients (19%) discontinued therapy because of an irAE, most commonly diarrhea. Overall, 103 patients (35%) required systemic corticosteroid treatment for an irAE; 29 (10%) also required anti-TNFα therapy. Defining TTF as either starting a new treatment or death, estimated median TTF was 5.7 months. Twelve percent of patients experienced long-term disease control without receiving additional antimelanoma therapy. OS and TTF were not affected by the occurrence of irAEs or the need for systemic corticosteroids. Conclusion IrAEs are common in patients treated with ipilimumab. In our experience, approximately one-third of ipilimumab-treated patients required systemic corticosteroids, and almost one-third of those required further immune suppression with anti-TNFα therapy. Practitioners and patients should be prepared to treat irAEs and should understand that such treatment does not affect OS or TTF.

scholarly journals Medical Comorbidities Assessed By CIRS Negatively Impact Survival in the Era of Targeted Therapies in CLL: A Multicenter Retrospective Analysis

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 918-918
Author(s):  
Max J Gordon ◽  
Stephen M Amrock ◽  
Xavier Issac Rivera ◽  
Spencer James ◽  
Sudhir Manda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Retrospective Analysis ◽  
Organ Dysfunction ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Time To Treatment ◽  
Time To Treatment Failure ◽  
The Impact

Abstract Introduction: The majority of patients with chronic lymphocytic leukemia (CLL) present with comorbidities, commensurate with the median age at diagnosis of 71 years. The Cumulative Illness Rating Scale (CIRS) is a widely used index which has been incorporated into clinical research in CLL. CIRS consists of 14 categories related to different body systems and scores the severity of each condition from 0-4. We have previously reported in a single-center study that CIRS predicted outcomes in patients with CLL treated with chemo-immunotherapy (CIT). However, to date it is not yet known how comorbidities impact outcomes in the era of novel agents. We tested a hypothesis that CIRS and severe organ dysfunction would retain prognostic significance. Methods: We conducted a retrospective analysis of patients with CLL who underwent treatment at three academic medical centers between 2000 and 2016. CIRS score was calculated as in Salvi et al, 2008. Overall survival (OS) and progression-free survival (PFS) were assessed by Cox proportional hazards models adjusting for performance status (PS), age group, and chemotherapy regimen. Survival analysis in patients treated with ibrutinib was adjusted for age, PS, Rai stage, del17p and prior treatment. In addition, the impact of severe organ dysfunction (CIRS-3+, i.e. CIRS score ≥3 in single organ system) was assessed. Results: Median age in patients receiving CIT was 65 years (N=233). The most common comorbidities were hypertension, endocrine (e.g. diabetes mellitus) and vascular (e.g. deep vein thrombosis). Fludarabine-Rituximab (N=61), Fludarabine-Cyclophosphamide-Rituximab (N=67), Rituximab-Cyclophosphamide-Vincristine-Prednisone (N=35), Bendamustine-Rituximab (N=38) and chlorambucil (N=47) were the most commonly used regimens. 79.5% of treatments were administered in a frontline setting. Average total CIRS was 6.6 and 47% had CIRS-3+. Median OS among all patients receiving CIT was 112 months (95% CI: 105 - 128 months). CIRS≥7 and CIRS3+ were associated with inferior OS compared to patients without significant comorbidities (87, 92 and 129 months, respectively, p<0.05). In multivariate analysis, OS and PFS both decreased with each increase in total CIRS by one point (HR=1.09; p=0.006 and HR=1.05; p = 0.02), while CIRS-3+ was associated with inferior OS among patients treated with CIT (HR=1.50, p=0.01). In patients treated with ibrutinib the median age was 71 years (N=83), which was significantly older than in the CIT cohort (p<0.001). The most common comorbidities were musculoskeletal (e.g., osteoarthritis), and gastrointestinal (e.g., acid reflux). Median follow up was 12 months (range, 1-39 months). Contrary to patients receiving CIT, 86% of patients had relapsed/refractory disease, with a median of 2 prior treatments (range 0-6). 35% had received prior fludarabine and 54% had received an alkylating agent. Average CIRS was 8.6 and 67% had CIRS-3+. Patients treated with ibrutinib who required dose reductions had higher CIRS (mean score 11.6 vs 7.6; p<0.0003). CIRS-3+ was also associated with dose reduction (RR=4.6, p=0.01). In multivariable analysis, time to treatment failure, defined as ibrutinib discontinuation due to either disease progression or intolerable side effects, shortened with each increase in total CIRS score by one point (HR=1.23; p<0.001). CIRS-3+ was similarly associated with increased risk of treatment failure in multivariable analysis (HR=3.80; p=0.02). In univariate analysis comparing low vs high CIRS (CIRS <7 vs CIRS≥7), median time to treatment failure was 37 vs 23 months (p=0.01; Fig. 1A). OS at 24 months was 100% vs 79% (p=0.02; Fig 1B). Conclusion: In this multicenter retrospective analysis we show that CIRS has prognostic significance in patients with CLL treated with either CIT or ibrutinib, where increased comorbidities correlate with shortened progression-free and overall survival. CIRS appears to carry prognostic value in both upfront and relapsed settings, including patients whose disease can be salvaged with ibrutinib. Larger prospective studies of patients with lymphoid malignancies who have comorbidities are necessary to better define the prognostic value of CIRS in the era of targeted agents and determine the optimal approach to therapy of such patients. Figure 1 Figure 1. Disclosures Persky: Genentech: Consultancy; MorphoSys: Other: Independent Data Monitoring Committee member ; Verastem: Consultancy; Spectrum Pharmaceuticals: Research Funding.

A phase III, double-blind, randomized study of nivolumab (NIVO) and ipilimumab (IPI), nivo monotherapy or placebo plus transarterial chemoembolization (TACE) in patients with intermediate-stage hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS349-TPS349
Author(s):  
Bruno Sangro ◽  
James J. Harding ◽  
Matthew Johnson ◽  
Daniel H. Palmer ◽  
Julien Edeline ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Intermediate Stage ◽  
The United States ◽  
Phase Iii ◽  
Locoregional Therapy ◽  
Double Blind ◽  
Free Survival

TPS349 Background: TACE is the most widely used locoregional therapy recommended for patients with intermediate-stage HCC (Barcelona Clinic Liver Cancer stage B). Despite the significant tumor responses that can be achieved with TACE, tumors commonly recur, progress, or are refractory. Clinical trials have explored the combination of TACE with tyrosine kinase inhibitors; however, these have not reported improved outcomes. HCC possesses a unique immunosuppressive microenvironment, which makes it an attractive target for immunotherapies, particularly immune checkpoint inhibitors. Furthermore, there is evidence that locoregional interventions induce changes in the immune environment that could promote synergy with checkpoint inhibitors. Preliminary data for the combination of TACE with nivolumab indicate an acceptable safety profile and promising efficacy (Harding et al. ASCO-GI 2020). NIVO monotherapy and NIVO+IPI combination therapy are both approved in the United States for patients with HCC previously treated with sorafenib. Together, these findings support investigation of TACE plus NIVO, IPI, or NIVO+IPI to address the therapeutic needs of patients with intermediate HCC. Methods: CheckMate 74W is a global, double-blind, placebo-controlled, 3-arm, randomized phase III trial. Patients with tumors that exceed the Beyond Milan and Up-to-7 criteria (7 being the sum of size [in centimeters] and number of tumors), eligible for TACE, with Eastern Cooperative Oncology Group performance status of 0 to 1 are eligible for enrollment. Patients must not have received prior locoregional therapies. Approximately 765 patients will be randomized in a 1:1:1 ratio to NIVO+IPI+TACE (arm A), NIVO+IPI placebo+TACE (arm B), or NIVO placebo+IPI placebo+TACE (arm C). Primary endpoints are the time to TACE progression (TTTP), assessed by blinded independent central review, and overall survival in arm A versus arm C. Secondary endpoints are TTTP and overall survival in arm B versus arm C, event-free survival, and progression-free survival. Clinical trial registry: NCT04340193. Clinical trial information: NCT04340193.

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