Rituximab Therapy after Response to R-CHOP Induction Therapy for Patients with Previously Untreated Indolent Non-Hodgkin’s Lymphoma (NHL): Clinical Outcomes and Pharmacokinetics (PK)

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1295-1295
Author(s):  
Louis Fehrenbacher ◽  
Jonathan A. Polikoff ◽  
Robert Hermann ◽  
Haresh Jhangiani ◽  
Jean Bjerke ◽  
...  
Keyword(s):  
Phase Iii ◽  
Open Label ◽  
Community Based ◽  
Serious Adverse Events ◽  
Residual Concentration ◽  
Ann Arbor ◽  
Grade 3 ◽  
To Receive ◽  
Ongoing Phase

Abstract The addition of rituximab (R) therapy significantly improves PFS in patients with relapsedl/refractory disease responding after CHOP as well as responders after R-CHOP induction (van Oers, 2005). The aim of this study was to assess, in patients with previously untreated indolent NHL, the safety, efficacy and PK of additional R therapy in responders to R-CHOP induction. Between 10/01 and 08/06, 102 patients aged 28–84 (mean 57 yr) yrs with Ann Arbor Stage III (28.4%) or IV (71.6%) indolent NHL were treated on this Phase II single-arm, open-label, multi-center, community-based trial. Baseline LDH and β2 microglobulin were above normal in 20.6% and 66.3% of patients, respectively. Treatment consisted of 6 cycles of R-CHOP (cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, and doxorubicin 50 mg/m2 all IV on Day 1 of each 21-day cycle; prednisone 100 mg/d po Days 1–5; and R 375 mg/m2 IV 2–3 days prior to first dose of CHOP and thereafter on Day 1 of each cycle). Patients with ongoing response (CR/CRu or PR) received R 375 mg/m2 weekly x 4, repeated every 6 months x 2 yrs, for a total of up to 16 R doses, within 28 days after completion of R-CHOP. Median follow-up was 39 mos. ORR after R-CHOP was 86.3% (95% CI: 78.3, 92.1), with CR/CRu 48% (95% CI: 38.0, 58.2). As measured from initiation of R-CHOP, PFS at 2 and 3 yrs was 75.2% (95% CI: 64.0, 83.3) and 67.3% (95% CI: 54.6, 77.2), respectively. OS at 2 and 3 yrs was 92.9% (95% CI: 85.7, 96.6) and 89.4% (95% CI: 81.2, 94.2), respectively. Infusion-related toxicity with R given after R-CHOP was less frequent than seen with R-CHOP in this study. The overall incidence of serious adverse events during R therapy given after R-CHOP was 8.5%, including 3 NCI-CTC grade 3/4 events: viral encephalitis (n=1), patellar fracture (n=1) & development of colon cancer (n=1). Serum R concentrations were collected over serial timepoints from 12 patients. Both pre- and end of infusion serum R concentrations were similar across cycles 2–4 of R therapy given after R-CHOP. R concentration was higher just prior to infusion of the first R dose given after R-CHOP due to residual concentration from the R-CHOP treatment. Concentrations were very low (< 10 ug/mL) just prior to initiation of the subsequent R cycles. During R therapy given after R-CHOP, serum R concentrations were similar to those previously reported during R monotherapy treatment (Berinstein, 1998). In summary, this study demonstrated that R therapy given after R-CHOP to be generally well-tolerated, and associated with 75.2% PFS and 92.9% OS at 2 yrs, and 67.3% PFS and 89.4% OS at 3 yrs. Moreover, the current study demonstrates that PK data from R induction can be extrapolated to R given after R-CHOP. The benefit of adding additional R therapy to responders to R-chemotherapy will be addressed in the analysis of the ongoing Phase III PRIMA study, wherein patients with advanced follicular lymphoma who respond to R-chemotherapy induction are randomized to receive further R therapy vs. observation.

Preliminary safety of bevacizumab with first-line Folfox, Capox, Folfiri and capecitabine for mCRC—First B.E.A.Trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3534-3534 ◽  
Author(s):  
S. R. Berry ◽  
D. Cunningham ◽  
M. Michael ◽  
M. Dibartolomeo ◽  
F. Rivera ◽  
...  
Keyword(s):  
Safety Data ◽  
Phase Iii ◽  
First Line ◽  
Community Based ◽  
Serious Adverse Events ◽  
Life Threatening ◽  
Large Phase ◽  
Arterial Thromboembolic Events ◽  
Grade 3

3534 Background: In a phase III pivotal trial in patients (pts) with metastatic colorectal cancer (mCRC), bevacizumab (BEV) increased overall survival by 30% when added to first-line IFL chemotherapy (CT). Safety data from controlled BEV trials have been described, and indicate that certain serious adverse events (SAE), primarily gastrointestinal (GI) perforations and arterial thromboembolic events (TE) occurred more often in pts who received CT with BEV than those who received CT alone. First BEAT was opened to evaluate safety events of BEV in a broader pt population using a variety of CT regimens. Methods: First BEAT started in June 2004 and aims to enrol up to 2000 mCRC pts in 41 countries. Eligible pts starting with first-line CT (physician’s choice) are treated until progression with BEV (5mg/kg q2w [5FU based CT] or 7.5mg/kg q3w [capecitabine based CT]). SAEs include deaths, new and prolonged hospitalizations, life-threatening as well as medically significant events and are reported within 24 hours. There BEV-relatedness is assessed by investigators. Results: By Dec 20, 2005, 1915 pts had been enrolled in 40 countries. 1603/1915 pts (male 58%; median age 59 years [29% were > 65 years]; PS 0–1 99%) had baseline data available for analyses. Median follow-up was 6.7 months (mean 7.3); 1509 pts had been followed-up for >60 days. The most common first-line CT regimens used with BEV were FOLFOX (28%), CAPOX (17%), FOLFIRI (25%) and capecitabine (8%). Among the 1603 pts that had started treatment with BEV, 638 SAEs were reported in 394 pts (25%). 60-day mortality was 2.4%. The most common SAE were diarrhoea 2.7% and pyrexia 2.2% and were usually not attributed as related to BEV. Related SAEs were reported in 132 (8%) pts. venous TE 1.7%, pulmonary embolism 1.1%, bleeding 1.0%, GI perforation 0.9%, arterial TE 0.8%, hypertension 0.5% wound healing complications 0.3% were usually classified as related SAEs. Conclusions: In this ongoing, large community-based study, the safety profile of BEV in first line mCRC pts receiving a variety of CT regimens, namely FOLFOX, CAPOX, FOLFIRI and capecitabine, appears consistent with that observed in large phase III randomised studies. Updated safety data, including grade 3/4 CTC toxicities, will be presented. [Table: see text]

scholarly journals Long Term Outcome of Lenalidomide-Dexamethasone (Rd) Vs Melphalan-Lenalidomide-Prednisone (MPR) Vs Cyclophosphamide-Prednisone-Lenalidomide (CPR) As Induction Followed By Lenalidomide-Prednisone (RP) Vs Lenalidomide (R) As Maintenance in a Community-Based Newly Diagnosed Myeloma Population: Updated Analysis of EMN01 Phase III Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 901-901
Author(s):  
Sara Bringhen ◽  
Massimo Offidani ◽  
Pellegrino Musto ◽  
Anna Marina Liberati ◽  
Giulia Benevolo ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Phase Iii ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Community Based ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Grade 3 ◽  
To Receive

Abstract Introduction : Rd and MPR showed to be effective combinations in elderly newly diagnosed multiple myeloma (NDMM) patients (pts). Cyclophosphamide is a less toxic alkylating alternative agent. EMN01 is the first trial to formally compare these three different Lenalidomide-based combinations. Maintenance with Lenalidomide has been recently approved in patients eligible for autologous stem cell transplant (ASCT). Few data are available about the best combination as maintenance in patients not eligible for ASCT. Methods : 662 pts with NDMM were randomized to receive 9 28-day cycles of Rd (lenalidomide 25 mg/day for 21 days; dexamethasone 40 mg on days 1,8,15 and 22 in pts 65-75 years old and 20 mg in those &gt;75 years), MPR (lenalidomide 10 mg/day for 21 days; melphalan orally 0.18 mg/Kg for 4 days in pts 65-75 years old and 0.13 mg/Kg in &gt;75 years pts; prednisone 1.5 mg/Kg for 4 days) or CPR (lenalidomide 25 mg/day for 21 days; cyclophosphamide orally 50 mg/day for 21 days in pts 65-75 years old and 50 mg every other day in &gt;75 years pts; prednisone 25 mg every other day). After induction, pts were randomized to receive maintenance with lenalidomide alone (R; 10 mg/day for 21 days) or with prednisone (RP; R, 10 mg/day for 21 days and P, 25 mg every other day), until disease progression. Results : Pts characteristics were well balanced in all groups; 217 pts in Rd, 217 in MPR and 220 in CPR arms could be evaluated. After a median follow-up of 63.7 months, median PFS was 23.2 months in MPR, 18.9 months in CPR and 18.6 months in Rd (MPR vs CPR p=0.02; MPR vs Rd p=0.08). Median overall survival (OS) was 79.9 months in MPR, 69.4 months in CPR and 68.1 months in Rd (MPR vs CPR p=0.98; MPR vs Rd p=0.64). The most common grade ≥3 adverse event (AEs) was neutropenia: 64% in MPR, 29% in CPR and 25% in Rd pts (p&lt;0.0001). Grade ≥3 non hematologic AEs were similar among arms. At the end of induction, 402 pts were eligible for maintenance, 198 in the RP and 204 in the R groups. PFS from start of maintenance was 22.2 months in the RP group and 17.6 in the R group, with 20% reduced the risk of death/progression for pts receiving RP maintenance (HR 0.81, p=0.07; Figure 1). A subgroup analysis was performed to determine the consistency of RP vs R treatment effect in different subgroups using interaction terms between treatment and cytogenetic abnormalities, ISS, age, sex, induction treatment and response before maintenance (Figure 1). No difference in OS was observed (HR 1.02, p=0.93) but the OS analysis was limited by the low number of events. Median duration of maintenance was 23.0 months in RP pts and 20.5 months in R pts, 14% and 13% of pts discontinued due to AEs, in RP and R groups, respectively. Conclusion : This phase III trial compared 2 different Lenalidomide-containing induction regimens and 2 different Lenalidomide-containing maintenance regimens in an elderly community-based NDMM population. MPR prolonged PFS by approximately 5 months, yet the higher incidence of hematologic toxicity should be carefully considered. The addition of low-dose prednisone to standard lenalidomide maintenance reduced the risk of death/progression by 20%, with a good safety profile. Updated results will be presented at the meeting. Disclosures Bringhen: Mundipharma: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Karyipharm: Membership on an entity's Board of Directors or advisory committees. Offidani: celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Musto: Celgene: Honoraria; Janssen: Honoraria. Gaidano: Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. De Sabbata: Celgene: Membership on an entity's Board of Directors or advisory committees. Palumbo: Sanofi: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Binding Site: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Genmab A/S: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Employment, Equity Ownership, Honoraria, Research Funding. Hájek: Amgen, Takeda, BMS, Celgene, Novartis, Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; Pharma MAR: Consultancy, Honoraria. Boccadoro: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial

2009 ◽  
Vol 27 (22) ◽  
pp. 3664-3670 ◽  
Author(s):  
Cyrille Hulin ◽  
Thierry Facon ◽  
Philippe Rodon ◽  
Brigitte Pegourie ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Elderly Patients ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Standards Of Care ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
To Receive

Purpose Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. Patients and Methods Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. Results After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). Conclusion This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.

A Phase III Study Of ASCT Vs Cyclophosphamide-Lenalidomide-Dexamethasone and Lenalidomide-Prednisone Maintenance Vs Lenalidomide Alone In Newly Diagnosed Myeloma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 763-763 ◽  
Author(s):  
Antonio Palumbo ◽  
Francesca Gay ◽  
Andrew Spencer ◽  
Francesco Di Raimondo ◽  
Adam Zdenek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Phase Iii ◽  
Study Endpoint ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Grade 3 ◽  
To Receive

Abstract Background High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). The introduction of novel agents challenged the role of ASCT at diagnosis. We conducted a multicenter 2X2 randomized trial comparing conventional chemotherapy plus lenalidomide with ASCT followed by maintenance with lenalidomide-prednisone (RP) or lenalidomide (R) alone in newly diagnosed young MM (NDMM) patients. Methods Eligible patients with NDMM ≤ 65 years were enrolled. All patients received Rd induction (four 28-day cycles of lenalidomide 25 mg day 1–21 and low-dose dexamethasone 40 mg day 1,8,15,22) followed by stem cell mobilization. Patients were randomized to receive consolidation with CRD [six 28-day cycles of cyclophosphamide (300 mg/m2 day 1,8,15), dexamethasone (40 mg days 1,8,15,22) and lenalidomide (25 mg days 1–21)] or MEL200-ASCT (melphalan 200 mg/m2 with stem-cell support). Patients were randomly assigned to receive subsequent maintenance with RP (28-day cycles of lenalidomide 25 mg days 1–21 plus prednisone 50 mg every other day) or R alone (28-day cycles of lenalidomide 25 mg days 1–21). Primary study endpoint was progression-free survival (PFS); secondary endpoints included safety, responses and overall survival (OS). Data cut off was May 30th, 2013. Results Three-hundred and eighty-nine patients were enrolled in the trial. Patient characteristics were well balanced between CRD (n=194) and MEL200-ASCT (n=195), and between R (n=195) and RP (n=194) arms. Median follow-up was 31 months. In the intent to treat (ITT) analysis, the median PFS was not reached with MEL200-ASCT and 28 months with CRD (the respective 3-year PFS was 60% vs. 38%, HR=0.62, 95%CI: 0.49-0.85, P=0.003). Median time from enrolment to maintenance was 14 months. In the population of patients eligible for maintenance, 2-year PFS from the start of maintenance was 73% for RP and 56% for R patients (HR= 0.57, 95%CI: 0.34-0.93; P=0.03). In the subgroup of patients who received MEL200-ASCT, 2-year PFS from the start of maintenance was 83% for patients who received RP and 64% for those who received R alone (HR=0.36 95%CI: 0.15-0.87, P=0.02). In the subgroup of patients who received CRD, 2-year PFS from the start of maintenance was 64% for patients who received RP and 47% for those who received R alone (HR=0.75, 95%CI: 0.40-1.39, P=0.36). At present, no differences in OS were noticed between patients randomised to received CRD or MEL200-ASCT, and between patients who received RP or R maintenance. As expected, the rates of grade 3-4 hematologic (85% vs. 26%, P<0.001) and non-hematologic (35% vs. 19%, P=0.003) adverse events (AEs) were higher in the MEL200-ASCT arm compared with the CRD arm. The main non-hematologic AEs were infections (18% vs. 5%, P=0.001) and gastrointestinal AEs (18% vs. 3%, P<0.001). Rates of grade 3-4 hematologic (8% vs. 7%, P=0.85) and non-hematologic (12% vs. 13%, P=0.88). AEs were similar in the RP and R arms. The main non-hematologic AEs in both RP and R groups were infections (3% vs. 3%). At present, 6 second primary malignancies and 3 cases of cutaneous basalioma have been reported. Conclusions MEL200-ASCT significantly prolonged PFS in comparison with CRD. At present no difference in OS was reported, this may be due to the low number of events and to the length of follow-up. The increase in toxicity with MEL200-ASCT did not adversely impact on efficacy. The addition of prednisone to lenalidomide maintenance significantly reduced the risk of progression in comparison with lenalidomide alone, without increasing the toxicity. Updated data with longer follow-up will be presented at the meeting. Disclosures: Palumbo: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria. Gay:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Spencer:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Larocca:Celgene: Honoraria. Caravita:Celgene: Honoraria, Research Funding. Petrucci:Celgene: Honoraria. Hajek:Celgene: Honoraria; Celgene: Consultancy. Boccadoro:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

DeCIDE: A phase III randomized trial of docetaxel (D), cisplatin (P), 5-fluorouracil (F) (TPF) induction chemotherapy (IC) in patients with N2/N3 locally advanced squamous cell carcinoma of the head and neck (SCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5500-5500 ◽  
Author(s):  
Ezra E. W. Cohen ◽  
Theodore Karrison ◽  
Masha Kocherginsky ◽  
Chao H Huang ◽  
Mark Agulnik ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Survival Rates ◽  
Phase Iii ◽  
High Survival ◽  
Open Label ◽  
Free Survival ◽  
Prior Therapy ◽  
Distant Failure ◽  
Grade 3

5500 Background: IC is associated with lower distant failure (DF) rates in SCCHN but an improvement in overall survival (OS) has not been validated. The goal of this trial was to determine whether IC prior to chemoradiotherapy (CRT) improves survival compared to CRT alone. Methods: In this phase 3, open-label trial, subjects with pathologically confirmed SCCHN; N2/N3 disease without metastases; no prior therapy; KPS ³ 70%; and intact organ function were randomized to CRT alone (CRT arm) [5 days of D (25 mg/m2), F (600 mg/m2), hydroxyurea (500 mg BID), and RT (150 cGy BID) followed by a 9 day break] or to 2 cycles of IC [D (75 mg/m2), P (75 mg/m2), F (750 mg/m2 day 1-5)] followed by the same CRT (IC arm). Primary endpoint was OS. Secondary endpoints included DF free survival, failure pattern, and recurrence-free survival (RFS). 280 subjects provided 80% power to detect a hazard ratio HR=0.5 for OS (a=0.05). Results: 280 subjects were accrued from 2004-09 with minimum follow-up 24 months. Of 142 patients randomized to IC, 91% received 2 cycles and 87% continued to CRT. Treatment adherence during CRT was high for docetaxel and hydroxyurea, but fewer than 75% of the patients received target dose of 5FU in both arms. RT was delivered without major deviations in 94% and 95% of patients on IC and CRT arms, respectively. The most common grade 3-4 toxicities during IC were febrile neutropenia (9%) and mucositis (8%), and during CRT (both arms combined) they were mucositis (45%), dermatitis (19%), and leukopenia (17%). Only grade 3-4 leukopenia and neutropenia rates were significantly higher in IC (p=0.002 and p=0.02, respectively). Table shows efficacy. Conclusions: High survival rates were observed in both arms. Further analysis and follow-up may provide insight into why the significant decrease in DF did not translate into improved OS. [Table: see text]

Afatinib monotherapy in patients with metastatic squamous cell carcinoma of the lung progressing after erlotinib/gefitinib (E/G) and chemotherapy: Interim subset analysis from a phase III trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7558-7558 ◽  
Author(s):  
Joo-Hang Kim ◽  
Francesco Grossi ◽  
Filippo De Marinis ◽  
Manuel Cobo ◽  
James Chih-Hsin Yang ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Treatment Options ◽  
Phase Iii ◽  
Open Label ◽  
Metastatic Nsclc ◽  
Erbb4 Receptor ◽  
Grade 3 ◽  
Patient Enrolment ◽  
Nsclc Patients ◽  
To Receive

7558 Background: Patients with squamous NSCLC have limited treatment options. For those deriving benefit from EGFR TKIs, it is unclear whether sustained ErbB family blockade offers benefit upon progression. We evaluated afatinib, an irreversible blocker of EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptor tyrosine kinases, in patients with metastatic NSCLC who had failed chemotherapy and E/G. Here we describe a pre-specified analysis of those with squamous histology in Part A. Methods: This randomized Phase III, open-label, multi-center trial enrolled patients with pathologically confirmed metastatic NSCLC after failing ≥1 line of cytotoxic chemotherapy and E/G. In Part A, patients received oral afatinib 50 mg until disease progression. Those with clinical benefit (≥12 wks) who progressed were eligible to receive afatinib plus paclitaxel or investigator’s choice chemotherapy (Part B). Primary endpoint was PFS (RECIST 1.1). Following an amendment, an interim analysis of Part A was performed to assess afatinib monotherapy. Results: Patient enrolment into Part A was from April 2010 to May 2011. Of 1154 afatinib-treated patients, 91 (8%) had squamous histology; 18/91 and 40/91 had CR/PR and SD on prior E/G, respectively (by investigator). Median age was 63 yrs, 71% were male, 76% were current/ex-smokers. Median PFS on afatinib was 3.7 mths in the squamous histology subset. Of 91 patients, 42 had PFS ≥3 mths; 13 had PFS of ≥6 mths. In evaluable patients (n=77), 1 CR and 3 PRs were confirmed; 51 and 22 patients had best overall response of SD and PD, respectively. Of the 31 patients with PD on prior E/G with no intervening chemotherapy, 10 achieved confirmed disease control (2 PR; 8 SD) on afatinib. Most commonly reported grade 3/4 adverse events (AEs) in Part A were diarrhea (13%) and rash/acne (12%). The safety profile in the squamous histology subset was similar to that observed for the whole trial. Conclusions: Afatinib monotherapy demonstrated encouraging activity in treatment-refractory NSCLC patients with squamous histology that merits further evaluation.

Hematologic Improvement, Transfusion Independence, and Safety Assessed Using Three Alternative Dosing Schedules of Azacitidine in Patients with Myelodysplastic Syndromes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2662-2662 ◽  
Author(s):  
Roger M. Lyons ◽  
Thomas Cosgriff ◽  
Sanjiv Modi ◽  
Heidi McIntyre ◽  
C.L. Beach ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Study ◽  
Transfusion Independence ◽  
Fab Classification ◽  
Common Grade ◽  
Grade 3 ◽  
To Receive

Abstract Efficacy and safety of azacitidine (Vidaza®), at the FDA-approved dosing schedule of 75 mg/m2/day x 7 days every 28 days, was demonstrated in a phase III CALGB study by Silverman et al (JCO2002; 20:2429) for the treatment of myelodysplastic syndromes (MDS). The objective of this phase II, multicenter, randomized, open-label study in all FAB subtypes of MDS was to study the treatment response and safety of 3 alternative subcutaneous azacitidine dosing schedules, eliminating the need for weekend azacitidine injections. Patients were randomized to either AZA 5-2-2 (75 mg/m2 day x 5 days, followed by 2 days no treatment, followed by 75 mg/m2/day x 2 days), AZA 5-2-5 (50 mg/m2/day x 5 days, followed by 2 days no treatment, followed by 50 mg/m2/day x 5 days) or AZA 5 (75 mg/m2/day x 5 days). After 6 cycles of azacitidine, patients meeting International Working Group MDS response/improvement criteria (Blood2000; 96:3671), defined as complete remission, partial remission, stable disease, or hematologic improvement, were eligible to receive an additional 12 cycles. As of July 1st, a total of 106 patients have been randomized in the AZA 5-2-2 (n=33), AZA 5-2-5 (n=35), and AZA 5 (n=38) treatment arms. Based on FAB classification, most patients have RA (42%, 45/106) or RAEB (30%, 32/106). Of 80 patients who have received ≥2 cycles of treatment, hematologic improvement (major or minor in at least 1 cell line) occurred in 58% (46/80) of the patients (Table). Median time to improvement in the 3 arms ranged between 1 and 3 cycles (AZA 5-2-2: 1.1, AZA 5-2-5: 3.0, AZA 5: 2.6). Of 38 patients who were RBC transfusion dependent at baseline, 27 (71%) became independent (AZA 5-2-2: 59%, 10/17, AZA 5-2-5: 89%, 8/9; AZA 5: 75%, 9/12). The most common grade 3 or 4 events included neutropenia 29%, 28/98 (AZA 5-2-2: 44%, 14/32; AZA 5-2-5: 20%, 6/30, and AZA 5: 22%, 8/36), thrombocytopenia 15%, 15/98 (AZA 5-2-2: 28%, 9/32; AZA 5-2-5: 10%, 3/30, and AZA 5: 8%, 3/36) and anemia 12%, 12/98 (AZA 5-2-2: 16%, 5/32; AZA 5-2-5: 17%, 5/30, and AZA 5: 6%, 2/36). The frequency of patients with a grade 3 or 4 infection was 15%, 15/98 (AZA 5-2-2: 19%, 6/32; AZA 5-2-5: 23%, 7/30; AZA 5: 6%, 2/36) or hemorrhage was 4%, 4/98 (AZA 5-2-2: 6%, 2/32; AZA 5-2-5: 7%, 2/30; AZA 5: 0/36). Updated data will be available at the time of the meeting. Based on preliminary results, these data indicate that the 3 alternative dosing schedules provide clinical benefit (i.e., transfusion independence and hematologic improvement) and are consistent with the FDA-approved 75 mg/m2/day x 7 days dosing results from previous CALGB studies. Table: Hematologic Improvement Response Rates

Phase III, randomized, open-label study of triweekly docetaxel versus biweekly docetaxel as treatments for advanced hormone-refractory prostate cancer: Findings from an interim safety analysis of the Finnish Uro-oncological Group Study 1-2003.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 129-129
Author(s):  
P. Hervonen ◽  
H. Joensuu ◽  
T. K. Joensuu ◽  
P. Nyandoto ◽  
M. Luukkaa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Performance Status ◽  
Safety Analysis ◽  
Similar Efficacy ◽  
Multicenter Trial ◽  
Phase Iii ◽  
Open Label ◽  
Serious Adverse Events ◽  
Hormone Refractory ◽  
Grade 3

129 Background: Docetaxel (T) administered at every three weeks is standard treatment for advanced HRPC. We compared 2-weekly to 3-weekly T as first- or second-line chemotherapy of advanced HRPC in this prospective randomized multicenter trial. Methods: 360 pts were randomly allocated to receive T 75 mg/m2 i.v. d1 q3 wks (tT) or 50 mg/m2 i.v. d1 and d 14, q4 wks (bT) from March 2004 to May 2009. Prednisolon 10 mg/day was administered in both groups. The groups were well balanced according to the WHO performance status, mean age (70 vs. 68, range 45–87), and the median serum PSA level at study entry (109 vs. 98 μ g/L, range 11–1,490). The primary endpoint was TTF. Study identifier: NCT00255606 . Results: 158 pts (tT, 79; bT, 79) were included in this preplanned interim safety analysis. 567 and 487 cycles were administered in the tT and bT groups, respectively. The most common grade 3–4 adverse events (expressed as %/cycles) in tT /bT were neutropenia 20%/14%, infection with/without neutropenia 8%/3%, fatigue 3%/ 3%, febrile neutropenia 2%/1%, and bone pain 2%/1%. Serious adverse events occurred more frequently in tT (n=60, 10.6% of cycles) than in bT (n=29, 6.0%, p=0.012). One pt. died from coronary infarction and one was diagnosed with ALL (both in bT group). 30 pts (38%) in bT group and 22 pts (28%) in tT group were receiving treatment at 6 months. (p=0.176). Conclusions: Biweekly T has been better tolerated than the conventional triweekly T with fewer serious adverse events and may be associated with similar efficacy. [Table: see text]

Open-label, phase IIIb, multicenter, expanded access study of everolimus in patients with advanced neuroendocrine tumors (NET).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4138-4138
Author(s):  
Oliver Edgar Bechter ◽  
Nicole Unger ◽  
Ivan Borbath ◽  
Sergio Ricci ◽  
Tsann-Long Hwang ◽  
...  
Keyword(s):  
Performance Status ◽  
Safety Data ◽  
Primary Objective ◽  
Phase Iii ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Expanded Access ◽  
Open Label Phase ◽  
Grade 3

4138 Background: Everolimus (EVE) antitumor efficacy in patients (pts) with advanced NET was demonstrated in 2 double-blind, placebo (P)–controlled, phase III trials (RADIANT-2 and RADIANT-3). Median PFS in pancreatic (pNET) pts was 11.0 months (EVE) vs. 4.6 months (P) (HR 0.35, 95% CI 0.27-0.45, P <0.001) in RADIANT-3. Median EVE exposure in RADIANT-3 was 38 wks. EVE was approved for advanced pNET in the US and Europe in 2011. An expanded access protocol was launched to gather additional safety data and provide access to EVE for pts with advanced NET while awaiting regulatory approval. Methods: Pts aged ≥18 years with biopsy-proven NET; WHO performance status 0-2; and adequate bone, hepatic, and renal function were enrolled. Main exclusion criteria were poorly differentiated NET and cytotoxic therapy within 4 wks of enrollment. EVE (10 mg/d) was administered until disease progression, unacceptable toxicity, discontinuation, death, commercial availability of EVE, or until May 30, 2012. Pts were enrolled from April 21, 2011 to April 20, 2012. Primary objective was grade 3/4 and serious adverse events (AEs). Secondary objectives included investigator-assessed best overall response rate and PFS. Results: The full analysis set included 246 pts (pNET, n=126; non-pNET, n=120); the safety set included 240 pts (pNET, n=123; non-pNET, n=117). Median age was 61 and 66 years; 54% and 49% were male. Main primary tumor sites in non-pNET pts included small intestine (40%) and lung (22%). Median duration of EVE exposure was 12.1 wks and 24 wks in pNET and non-pNET. At data cutoff, there were 21 and 32 PFS events; 105 and 88 pts were censored. Grade 3/4 AEs were reported in 42.3% and 69.2% of pNET and non-pNET; those reported in ≥10% of pts in pNET and non-pNET included hyperglycemia (12.2% and 5.1%), diarrhea (10.6% and 31.6%), stomatitis (9.8% and 11.1%), nausea (8.1% and 10.3%), and anemia (5.7% and 11.1%). Median investigator-assessed PFS was 7.6 (95% CI 5.52-7.62) months and 10.8 (8.77-Not Estimable) months in pNET and non-pNET. Conclusions: EVE was well tolerated in pts with advanced NET. AEs were similar to those previously reported. Protocol-specified early termination of pts limits the interpretation of PFS medians. Clinical trial information: EudraCT Number: 2010-023032-17.

APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4000-4000 ◽  
Author(s):  
Margaret A. Tempero ◽  
Michele Reni ◽  
Hanno Riess ◽  
Uwe Pelzer ◽  
Eileen Mary O'Reilly ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Disease Recurrence ◽  
Geographic Region ◽  
Phase Iii ◽  
Lymph Node Status ◽  
Open Label ◽  
Significance Level ◽  
Grade 3 ◽  
Ecog Ps

4000 Background: In metastatic pancreatic cancer (PC), nab-P/G demonstrated significantly longer overall survival (OS) vs G. APACT assessed efficacy & safety of nab-P/G vs G in surgically resected PC. Methods: Treatment (tx)-naive patients (pts) with histologically confirmed PC, macroscopic complete resection, ECOG PS 0/1, & CA19-9 < 100 U/mL were eligible. Stratification factors: resection status (R0/R1), lymph node status (LN+/−), & geographic region. Tx was initiated ≤ 12 wks postsurgery. Pts received nab-P 125 mg/m2 + G 1000 mg/m2 or G 1000 mg/m2 on days 1, 8, 15 of six 28-day cycles. Primary endpoint was disease-free survival (DFS) by independent reviewer (IR); IRs received baseline clinical data & scans. Secondary endpoints were OS & safety. ≈438 DFS events were needed for 90% power to detect an HR for disease recurrence or death of 0.73 with nab-P/G vs G at a 2-sided significance level of 0.05. Results: 866 pts were randomized. Median age was 64 y (range, 34 - 86); most pts had ECOG PS 0 (60%), LN+ (72%), & R0 (76%). 69% of pts completed 6 tx cycles ( nab-P/G, 66%; G, 71%). Median follow up for OS was 38.5 mo. Median IR-assessed DFS (439 events) was 19.4 mo ( nab-P/G) vs 18.8 mo (G) (HR, 0.88; 95% CI, 0.729 - 1.063; stratified log-rank P = 0.1824). Investigator-assessed DFS (571 events) was 16.6 mo ( nab-P/G) vs 13.7 mo (G) (HR, 0.82; 95% CI, 0.694 - 0.965; nominal P = 0.0168). Interim OS (427 events) was 40.5 mo ( nab-P/G) vs 36.2 mo (G) (HR, 0.82; 95% CI, 0.680 - 0.996; nominal P = 0.045). Grade ≥ 3 TEAEs were reported in 86% vs 68% of pts with nab-P/G vs G. The most common grade ≥ 3 hematologic & nonhematologic TEAEs with nab-P/G vs G were neutropenia (49% vs 43%) & fatigue (10% vs 3%). TEAEs led to death in 2 pts in each arm. Conclusions: IR DFS with nab-P/G was not significantly longer vs G; median DFS with G was longer than historical data. DFS by investigator (sensitivity analysis) and interim OS were improved with nab-P/G vs G (HR 0.82 for both). Adjuvant nab-P/G may be an option for pts who are ineligible for FOLFIRINOX. Additional OS follow-up may better support nab-P/G as an option in the adjuvant setting. Clinical trial information: NCT01964430.

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