Gemcitabine and cisplatin (GP) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC): A phase 3, multicenter, randomized controlled trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6003-6003 ◽  
Author(s):  
Jun Ma ◽  
Yuan Zhang ◽  
Ying Sun ◽  
Fangyun Xie ◽  
Weihan Hu ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Intensity Modulated Radiotherapy ◽  
Free Survival ◽  
Intention To Treat ◽  
Multicenter Randomized Controlled Trial ◽  
Common Grade ◽  
Grade 3 ◽  
To Receive ◽  
Treat Population

6003 Background: GP regimen has been established as the standard first-line treatment option for patients with recurrent/metastatic NPC. However, its efficacy in locoregionally advanced disease remains unclear. Methods: Patients with previously untreated, non-metastatic stage III-IVB (except T3-4N0M0, AJCC 7th) NPC, aged 18–64 years without severe comorbidities were eligible. They were randomly assigned (1:1) to receive GP IC (gemcitabine 1 g/m2on days 1 & 8, cisplatin 80 mg/m2 on day 1, q3w for 3 cycles) plus CCRT (cisplatin 100 mg/m2, q3w for 3 cycles, concurrently with intensity-modulated radiotherapy) or CCRT alone. The primary endpoint was failure-free survival (FFS). The calculated sample size was 238 per group, with an 80% power (two-sided α 0.05) to detect a treatment failure hazard ratio (HR) of 0.52. Results: From Dec 2013 to Sep 2016, 480 patients from 12 centers were randomly assigned to IC+CCRT (n = 242) or CCRT alone (n = 238) group. Baseline characteristics were well balanced. After a median follow-up of 39 months, 3-year FFS was 85.8% in the IC+CCRT group and 77.2% in the CCRT alone group (intention-to-treat population; HR 0.53, 95% confidence interval 0.34–0.81; P = 0.003). In GP+CCRT group, 239 patients started GP IC and 231 (96.7%) completed all three cycles. The most common ≥grade 3 adverse events (AE) in IC+CCRT and CCRT group were mucositis (28.9% vs. 32.1%), neutropenia (28.0% vs. 10.5%) and leukopenia (26.4% vs. 20.3%). Conclusions: Adding GP IC to CCRT significantly improved FFS in locoregionally advanced NPC and is well tolerated with favorable toxicity profile. Clinical trial information: NCT01872962. [Table: see text]

Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3107-3114 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Anna M. Liberati ◽  
Tommaso Caravita ◽  
Antonietta Falcone ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Progression Free Survival ◽  
Staging System ◽  
Survival Advantage ◽  
Free Survival ◽  
Intention To Treat ◽  
International Staging System ◽  
Relapsed Disease ◽  
To Receive

Abstract The initial analysis of the oral combination melphalan, prednisone, and thalidomide (MPT) in newly diagnosed patients with myeloma showed significantly higher response rate and longer progression-free survival (PFS) than did the standard melphalan and prednisone (MP) combination and suggested a survival advantage. In this updated analysis, efficacy and safety end points were updated. Patients were randomly assigned to receive oral MPT or MP alone. Updated analysis was by intention to treat and included PFS, overall survival (OS), and survival after progression. After a median follow-up of 38.1 months, the median PFS was 21.8 months for MPT and 14.5 months for MP (P = .004). The median OS was 45.0 months for MPT and 47.6 months for MP (P = .79). In different patient subgroups, MPT improved PFS irrespective of age, serum concentrations of β2-microglobulin, or high International Staging System. Thalidomide or bortezomib administration as salvage regimens significantly improved survival after progression in the MP group (P = .002) but not in the MPT group (P = .34). These data confirm activity of MPT for PFS but failed to show any survival advantage. New agents in the management of relapsed disease could explain this finding. The study is registered at www.clinicaltrials.gov as #NCT00232934.

Folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) plus chemoradiation (CRT) with 5-fluorouracil (5FU) as adjuvant treatment for patients with operable gastric cancer (OGC): A feasibility study with pharmacogenetic analysis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 44-44
Author(s):  
A. Athanasiadis ◽  
I. Boukovinas ◽  
M. Sfakianaki ◽  
Z. Saridaki ◽  
C. Papadaki ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Drug Exposure ◽  
Free Probability ◽  
Disease Free Survival ◽  
Free Survival ◽  
Probability Of Survival ◽  
Common Grade ◽  
Grade 3 ◽  
Median Rate

44 Background: To evaluate the efficacy and safety of FOLFIRI plus CRT with 5FU as adjuvant treatment for patients with OGC. Methods: Patients received treatment with FOLFIRI (irinotrecan 150 mg/m2, d1, LV 200 mg/m2, d1+2 and 5FU [400 mg/m2/d bolus and 600 mg/m2/d, 22 h infusion, d1+2]) for 2 15-day cycles followed by RT (45Gy) with 5FU continuous infusion (325 mg/m2/d in the 1st and 5th week) administration. Eight additional cycles of FOLFIRI were administered after the completion of CRT. BRCA1, ERCC1, XPD, TOPO-I, TOPO-IIA and B and TS mRNA expression was determined in the primary tumor where available. Results: The median age of the 171 enrolled patients was 62 years, 114 (66%) were males, 136 (79%) had R0 resections and 152 (89%) had at least a D1 resection. Treatment was completed as per protocol in 107 (63%) of the patients. CRT was completed in all but 5 (3%) patients. The median rate of drug exposure was 93% for irinotecan, 87% for 5FU and 91% for LV. The most common grade 3/4 adverse events were neutropenia (32%), febrile neutropenia (3.5%) and diarrhea (7%). After a median follow-up of 45.7 months 84 had relapsed and 70 were deceased. The median disease-free survival (DFS) was 30 months (95% CI: 18-41 months), while the projected median overall survival (mOS) was 53.7 months (95% CI: 30-77 months). The recurrence free probability at 5 years was 44% while the probability of survival at 5 years was 46%. From the studied pharmacogenetic markers only TS low expression was correlated with a trend towards improved DFS and OS in patients with R0 resections. Conclusions: These results show that the administration of FOLFIRI plus CRT with 5FU as adjuvant treatment in OGC is a feasible approach with acceptable toxicity and challenging efficacy which merits further evaluation in a randomized trial. No significant financial relationships to disclose.

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3575-3575
Author(s):  
Tamas Pinter ◽  
Esteban Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

3575 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. his trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally-advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

scholarly journals Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004

Blood ◽  
2012 ◽  
Vol 120 (5) ◽  
pp. 978-984 ◽  
Author(s):  
Henrik Hasle ◽  
Jonas Abrahamsson ◽  
Erik Forestier ◽  
Shau-Yin Ha ◽  
Jesper Heldrup ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Severe Neutropenia ◽  
Free Survival ◽  
Intention To Treat ◽  
A Minor ◽  
Time To Relapse ◽  
To Receive

Abstract There are no data on the role of postconsolidation therapy with gemtuzumab ozogamicin (GO; Mylotarg) in children with acute myeloid leukemia (AML). The NOPHO-AML 2004 protocol studied postconsolidation randomization to GO or no further therapy. GO was administered at 5 mg/m2 and repeated after 3 weeks. We randomized 120 patients; 59 to receive GO. Survival was analyzed on an intention-to-treat basis. The median follow-up for patients who were alive was 4.2 years. Children who received GO showed modest elevation of transaminase and bilirubin without signs of veno-occlusive disease. Severe neutropenia followed 95% and febrile neutropenia 40% of the GO courses. Only a moderate decline in platelet count and a minor decrease in hemoglobin occurred. Relapse occurred in 24 and 25 of those randomized to GO or no further therapy. The median time to relapse was 16 months versus 10 months (nonsignificant). The 5-year event-free survival and overall survival was 55% versus 51% and 74% versus 80% in those randomized to receive GO or no further therapy, respectively. Results were similar in all subgroups. In conclusion, GO therapy postconsolidation as given in this trial was well tolerated, showed a nonsignificant delay in time to relapse, but did not change the rate of relapse or survival (clinicaltrials.gov identifier NCT00476541).

Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival

2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Complete Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Grade 3 ◽  
To Receive

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

Updated survival results of the randomized phase II study comparing cisplatin/capecitabine (CX) with epirubicin plus CX (ECX) in advanced gastric cancer (AGC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 46-46 ◽  
Author(s):  
T. Lim ◽  
J. Yun ◽  
J. Lee ◽  
S. Park ◽  
J. Park ◽  
...  
Keyword(s):  
Performance Status ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
To Receive ◽  
Line Chemotherapy

46 Background: We previously reported results of a randomized study showing that CX is equally active to ECX in terms of progression-free survival (PFS) (Yun et al. Eur J Cancer. 2010). Here we report updated overall survival (OS) results with an additional 12 months' follow-up. Methods: Ninety-one chemotherapy-naïve patients with histologically-confirmed, measurable AGC were randomized to receive CX (cisplatin 75 mg/m2 iv on day 1 and capecitabine 1,000 mg/m2 bid po on days 1-14, n=45) or ECX (epirubicin 50 mg/m2 plus CX, n=44) every 3 weeks. After CX or ECX had failed, second-line chemotherapy (SLC) was recommended for all patients if their performance status was preserved. Results: Treatment duration was similar for both arms (4.4 for CX v 4.2 months for ECX). There was no relevant difference in the occurrence of overall grade 3 or 4 toxicities between the CX and ECX arms (80% v 78%, respectively; p=0.516). However, none in the CX and 12% in the ECX arm discontinued treatment because of toxicity. There were no significant differences in therapeutic efficacy between CX and ECX with respect to the response rate (38% v 37%, respectively), PFS (6.4 v 6.5 months), as well as OS (12.7 v 13.8 months; p=0.51). After failure, 60% of patients (26 CX and 28 ECX patients) received SLC. However, OS was not differed whether a patient was treated with SLC or not (13.1 v 11.2 months; p=0.94). Conclusions: The present analysis confirms previous findings that both CX and ECX appear to be comparatively active as first-line chemotherapy for AGC. Furthermore, the role of SLC in AGC warrants further evaluation. No significant financial relationships to disclose.

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. LBA445-LBA445 ◽  
Author(s):  
Tamas Pinter ◽  
Steve Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

LBA445 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. This trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See Table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

scholarly journals CTNI-38. PAMIPARIB IN COMBINATION WITH RADIATION THERAPY (RT) AND/OR TEMOZOLOMIDE (TMZ) IN PATIENTS WITH NEWLY DIAGNOSED (ND) OR RECURRENT/REFRACTORY (R/R) GLIOBLASTOMA (GBM); PHASE 1B/2 STUDY UPDATE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii51-ii51
Author(s):  
Anna Piotrowski ◽  
Vinay Puduvalli ◽  
Patrick Wen ◽  
Howard Colman ◽  
Jian Campian ◽  
...  
Keyword(s):  
Rest Period ◽  
Progression Free Survival ◽  
Free Survival ◽  
Synergistic Cytotoxicity ◽  
Common Grade ◽  
Duration Of Response ◽  
Phase 1B ◽  
Grade 3 ◽  
Parp 1

Abstract Pamiparib, an investigational, oral PARP 1/2 inhibitor, demonstrated preclinical brain penetration and synergistic cytotoxicity with TMZ. We report updated safety and antitumor data for pamiparib plus RT and/or TMZ in ND-GBM or R/R-GBM (SNO 2019, ACTR-39). This dose-escalation/expansion study includes three arms: A, pamiparib (2, 4, or 6 weeks) plus RT (6–7 weeks) in ND-GBM with unmethylated MGMT promoter (unmethylated-GBM); B, pamiparib (6 weeks) plus RT and increasing TMZ doses in Weeks 1 and 5 of RT in unmethylated ND-GBM; and C, pamiparib plus increasing TMZ doses in methylated/unmethylated R/R-GBM. Most patients in Arms A (expansion) and B received maintenance pamiparib plus TMZ after post-RT rest period at Arm C expansion. As of April 10, 2020, enrollment was complete (N=116; A, n=60; B, n=9; C, n=47). Median study follow-up was 11.3 mo (A/B) and 7.1 mo (C). Common grade ≥3 AEs were anemia (10%) in Arm A; decreased neutrophil and white blood cell count (each 22%) in B; anemia, fatigue, and decreased lymphocyte count (each 11%) in C. Brain edema (A) and pneumonia (C) (n=1 each) were fatal treatment-unrelated AEs. In ND-GBM, modified disease control rate (DCR following post-RT rest period) was 69.8% (95% CI, 55.7–81.7) overall, 68.8% (50.0–83.9) in A, and 80.0% (28.4–99.5) in B. Median duration of response was 5.1 mo (overall), 3.8 mo (A), and NE (B). In Arms A/B, median progression-free survival (PFS) and median overall survival (OS) were 4.4 mo and 12.7 mo, respectively; 12-mo OS rate, 54% (95% CI, 40–66). In R/R-GBM (Arm C), confirmed ORR was 9.1% (95% CI, 2.5–21.7); median PFS and OS were 1.9 mo and 7.3 mo, respectively; 6-mo PFS rate, 19% (95% CI, 9–32). These results showed a manageable safety profile for pamiparib +/- RT +/-TMZ; response and survival results support further evaluation of these combinations in GBM.

Neoadjuvant atezolizumab (A) with gemcitabine and cisplatin (GC) in patients (pts) with muscle-invasive bladder cancer (MIBC): A multicenter, single-arm, phase 2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4517-4517
Author(s):  
Samuel Aaron Funt ◽  
Michael Lattanzi ◽  
Karissa Whiting ◽  
Hikmat A. Al-Ahmadie ◽  
Colleen Quinlan ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Pancreatic Enzyme ◽  
Phase 2 Trial ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Enzyme Elevation ◽  
To Receive

4517 Background: Neoadjuvant GC is standard for pts with MIBC and can result in pathologic downstaging to non-MIBC ( < pT2N0) at radical cystectomy (RC), which correlates with improved survival. Based on the known activity of A in metastatic BC (mBC), we tested the combination of GC+A as neoadjuvant therapy for MIBC in a phase II trial (NCT02989584). Methods: Eligible pts with MIBC (cT2-T4aN0M0) received a single dose of A (1200 mg IV) and, two weeks later, began C (as either 70mg/m2 IV on D1 or 35 mg/m2 on D1,D8), G (1000 mg/m2 on D1,D8), and A (1200 mg IV on D8) every 21 days for 4 cycles followed by RC. Pts were also able to receive one additional dose of A 3 weeks after the last dose of A and prior to RC. The primary endpoint was proportion of pts with < pT2N0. Pts were considered not evaluable for the primary endpoint if they received less than 2 cycles due to withdrawal of consent or unrelated adverse events (AEs). Secondary endpoints included the proportion of pts with pT0N0, recurrence-free survival (RFS), and safety. We prespecified null and alternate < pT2N0 rates of 35% and 55%, respectively, with the null being rejected if at least 19 of 39 pts achieved < pT2N0. Pretreatment tumors underwent centralized PD-L1 staining (SP142; positive if ≥5% of immune cells). Results: Between Feb 2018 and May 2020, 44 pts were enrolled from five institutions. Five pts were not evaluable (withdrawal of consent before C3, n = 4; unrelated AEs during C1, n = 1). Of the 39 evaluable pts (cT2N0 79%, cT3N0 18%, cT4N0 3%), 1 pt refused surgery and was considered a non-responder. The primary endpoint was met, with 27 of 39 pts (69%) < pT2N0 at RC, including 15 (38%) pT0N0. All pts achieving < pT2N0 are alive and disease free. The median RFS was not reached with a median follow-up of 16.7 months (range: 7.7-33.2). The median time from last dose of chemotherapy to RC was 7.8 weeks (range 5.1 – 17). The most common grade 3-4 treatment related AEs were due to chemotherapy and were neutropenia (36%), lymphopenia (16%), and anemia (11%). Possible grade 3-4 immune related AEs included 2 pts with asymptomatic grade 3 pancreatic enzyme elevation, 1 pt with grade 3 pancreatitis, and 1 pt with hepatitis requiring steroids. Only 4 of 39 (10%) pts had PD-L1 positive tumors, which is low compared to mBC (25% positive; Powles et al. Lancet 2017) and MIBC (40% positive; Powles et al. Nature Med 2019) cohorts also tested with the SP142 clone. All 4 pts with PD-L1 positive tumors achieved < pT2N0. Twelve of 12 (100%) non-responding pts were PD-L1 negative and 23 of 27 (85%) responding pts were PD-L1 negative (p = 0.3). Conclusions: Neoadjuvant GC+A is an effective and safe regimen for the treatment of pts with MIBC. The PD-L1 positivity rate was low compared with other studies and was not predictive of pathologic downstaging. Additional interrogation of the genomic and host immune factors mediating response and resistance to GC+A is ongoing. Clinical trial information: NCT02989584.

A Prospective, Randomized Study of Melphalan, Prednisone, Lenalidomide (MPR) versus Melphalan (200 Mg/M2) and Autologous Transplantation (Mel200) in Newly Diagnosed Myeloma Patients: An Interim Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 350-350 ◽  
Author(s):  
Antonio Palumbo ◽  
Federica Cavallo ◽  
Dina Ben Yehuda ◽  
Paola Omedè ◽  
Agostina Siniscalchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
New Drugs ◽  
Thromboembolic Events ◽  
Free Survival ◽  
Cd34 Cells ◽  
Grade 3 ◽  
To Receive

Abstract Abstract 350 Background. The incorporation of new drugs as induction therapy before autologous transplantation appears to produce a high proportion of complete responses, slightly superior to those achieved by conventional chemotherapy with new drugs. Randomized trials are needed to directly compare current best chemotherapeutic approach with best autologous transplantation strategy. Aims. To compare melphalan, prednisone and lenalidomide (MPR) with tandem melphalan (200 mg/m2) (MEL200) in patients younger than 65 years. Methods. As induction, all (N=402) patients received four 28-day cycles of lenalidomide (25 mg days 1-21) and low-dose dexamethasone (40mg days 1,8,15,22) (Rd). Cyclophosphamide (4 g/m2) plus granulocyte-colony stimulating factor was used to mobilize stem cells. As consolidation, patients (N=202) randomized to MPR received six 28-day cycles of melphalan (0.18 mg/kg days 1-4), prednisone (2 mg/kg days 1-4) and lenalidomide (10mg days 1-21); patients (N=200) randomized to MEL200 received tandem melphalan 200 mg/m2 with stem-cell support. All patients were also randomized to receive either aspirin or low-molecular weight heparin (enoxaparin) as thromboprophylaxis. Primary end point was progression-free survival; data were analyzed in intention-to-treat. Results. Patient characteristics were similar in both groups, median age was 58 years. After Rd induction, at least partial response (PR) rate was 84%, at least very good partial response (VGPR) was 32% including 5% complete response (CR). The median yields of CD34+ cells harvested was 10 ×106 CD34+ cells/Kg; 94% of patients collected the minimum dose of 2×106/kg CD34+ cells. After 3 cycles of MPR, at least VGPR rate was 51% and CR 11%. After the first MEL200, at least VGPR rate was 56% and CR 14%. No difference in responses were reported according to cytogenetic abnormalities, such as del13, t(4;14) and t(14;16). After a median follow-up of 12 months, 1-year progression-free survival was 96% for MPR and 94% for MEL200 (p=.92) 1-year overall survival was 98% for MPR and 99% for MEL200 (p=.94). During Rd induction, the most frequent grade 3-4 adverse events were neutropenia (9%), anemia (8%), infections (4%), skin rash (4%), fatigue (2%) and thromboembolic events (1%). During consolidation, the incidence of grade 3-4 neutropenia (97% vs 34%, p <.001) thrombocytopenia (97% vs 16%, p<.001), infections (21% vs 3%, p<.001) and gastrointestinal (17% vs 1%, p<.001) complications was higher in MEL200 patients The incidence of thromboembolic events was similar in patients randomized to receive aspirin (2%) or enoxaparin (1%) as thromboprophylaxis (p=.42). Conclusion. Rd is an effective and safe induction regimen. Both MPR andMEL200 improved the quality of response, achieved by Rd induction. At present, progression-free and overall survival are not significantly different in the two groups, but longer follow-up is needed. Both aspirin and enoxaparin were equally effective as thromboprophylaxis. These data will be updated at the meeting. Disclosures: Palumbo: CELGENE: Honoraria. Cavallo:CELGENE: Honoraria. Patriarca:CELGENE: Honoraria. Caravita:CELGENE: CONSULTANCY. Boccadoro:CELGENE: CONSULTANCY, ADVISORY COMMITTEES, Research Funding.

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