Efficacy Of BV Research Articles

Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma.

The goal of therapy in pediatric Hodgkin lymphoma (HL) is to maximize overall survival while minimizing the morbidity of curative therapy. Key findings from recent Children's Oncology Group (COG) trials include: (i) superior event-free survival with the addition of brentuximab vedotin (Bv) in frontline regimens for high-risk disease, (ii) successful reduction in myeloablative regimens with demonstrated safety and efficacy of Bv and checkpoint inhibitor therapy in relapsed disease, and (ii) the potential to select a population that can be salvaged after relapse without receiving a stem cell transplant. The COG HL committee will lead a National cancer Institute National Clinical Trials Network phase 3 trial to evaluate the combination of Bv/nivolumab in early-stage disease. Ongoing advances in technology and blood biomarkers are increasing the ability to deliver biologically driven, personalized treatment for HL.

The Short-Term Efficacy and Safety of Brentuximab Vedotin Plus Cyclophosphamide, Epirubicin and Prednisone in Untreated PTCL: A Real-World, Retrospective Study.

IntroductionBrentuximab vedotin (BV) showed high overall remission rates in refractory/relapsed classical Hodgkin’s lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Although the efficacy of BV has been reported in clinical trials, its efficacy as a frontline therapy in real world for patients with CD30 positive subtypes of non-Hodgkin’s lymphoma (NHL) such as peripheral T-cell lymphoma with T-follicular helper cell (TFH) phenotype (PTCL, TFH), anaplastic large-cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL) in China has not been well documented.MethodsAnalysis of a real-world, observational, retrospective case series in patients suffering from AITL, sALCL and peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH) and other types of PTCL treated with BV in frontline treatment was conducted. The patients were given treatment from May 2020 till June 28, 2021. All patients were pathologically diagnosed to have PTCL before treatment and expressed CD30. Patients received BV (1.8 mg/kg) combined with CEP (cyclophosphamide, epirubicin, prednisone acetate every 3 weeks). The primary endpoint was objective response rates (ORR), and secondary endpoints were duration of response and incidence of adverse events (AEs). Exploratory endpoints such as progression-free survival (PFS) are discussed even though after such a short period.ResultsNineteen patients completed ≥ 1 cycles of BV-CEP treatment (16 cases completed ≥ 4 cycles, 3 cases only completed 1 cycle). Among them, the ORR reached 89.5% [CR 52.7%; partial response (PR) 36.8%]. In the ALCL group, CR reached 100% with the median duration of response of up to 8 months, while in the AITL group, the ORR was 75% and 2 patients had disease progression after treatment with BV + CEP. We also observed that BV-CEP may extend the PFS compared to traditional chemotherapy such as the CHOEP regimen (BV-CEP: not evaluable, CHOEP: 6.5 months), although the median follow-up was only 6.7 months. Adverse events (AEs), including incidence and severity of febrile neutropenia (26% patients in the BV-CEP group and 30% in the CHOEP group), were similar between groups. There was no incidence of AEs leading to treatment withdrawal or death under BV-CEP treatment.ConclusionBV is a promising treatment in patients with ALCL, AITL and PTCL-TFH in frontline treatment settings.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01943-z.

Long-Term Results of Brentuximab Vedotin in Relapsed and Refractory Hodgkin Lymphoma: Multi-Center Real-Life Experience

Introduction:In classical Hodgkin lymphoma (cHL), approximately a third of patients will relapse after first-line therapy and 15% will fail both first and second line therapies, and therapeutic options are still quite limited in these patients. Several studies have shown the efficacy of BV in relapsed/refractory HL patients .We previously reported the primary results of 58 named patient program (NPP) patients, with an objective response rate (ORR) of 63.5% (CR rate: 26.5%) . Here we present the long-term results of cohort (Salihoglu et al. Ann Hematol 2015).Design and Methods:Eleven Turkish institutions participated in this multicenter, retrospective study. Patients were included without any limitations regarding performance status and organ function. All of the patients provided written informed consent. BV is imported via the named-patient-program. BV was given at approved standart dosage.Results:From March 2011 to July 2013, 58 patients were included in the named patient program (table 1) and they were treated with BV and followed-up until July 2017, 4 years after the last time of initiation of BV. Ten patients remained in remission (8 CRs and 2 PRs) without the initiation of new therapy other than stem cell transplantation (SCT). These 10 patients has a median observation time of 54.5 months (range: 10-64 months) and the median observation time for all patients from the first dose was 18.5 months (range: 4-66 months). The median OS and PFS were 19 months (95% CI:0.37-0.63) and 5.5 months (95% CI:0.34-0.59), respectively. The estimated 5-year OS and PFS rates were 25% (95% CI:0.15-0.37) and 12% (95% CI:0.03-0.27), respectively (Table 2; Figure 1 A&B).Among our cohort, 36 (62%) received ≥1 anticancer therapy following BV. Twenty-four patients had SCT following BV treatment; 3, 11, and 8 auto-, allo-, and haplo-SCTs were performed, respectively; and 2, 4, 2 patients received auto-, allo- and haplo-SCT as consolidative therapy following BV, respectively. One and 1 patient received allo- and haplo-SCT as second-line treatment subsequent to BV, respectively. Excluding SCT conditioning regimens; 14 and 10 patients received single and multi agent therapy following BV, respectively. Excluding consolidative SCT, median numbers of subsequent treatments was 1 (range: 1-5).Eighteen of 58 patients (31%) achieved a CR during the follow-up, and better survival outcomes were observed in this group. The median of duration of response was 42 months (range: 2-59 months). The estimated 5-year OS and PFS rates were 59% (95% CI:0.33-0.79) and 34% (95% CI:0.07-0.63), respectively (Figure 1 C&D).Among 15 patients that were in remission at the time of analysis, of 7 patients that remained in the follow-up and in remission, three had consolidative SCT (1 auto- and 2 allo-SCTs) and 4 received no further cancer treatment (22% of all CR patients). Additionally, we should state that one patient, who received no further treatment after BV and who was in CR, died due to lung cancer an 41st month of follow-up.Of the 18 patients who achieved CR after BV, six patients had a consolidative SCT as their next therapy following BV (2 auto-, 3 allo- and 1 haplo-SCT). Additionally, one CR patient underwent haplo-SCT after having had progressive disease. Among 6 patients that had consolidative SCT following achievement of CR, the estimated 5-years OS and PFS rates were 67% (95% CI:0.19-0.90) and 67% (95% CI:0.19-0.90), respectively. For the resting 12 CR patients, the estimated 5-years OS and PFS rates were 55% (95% CI:0.23-0.78) and 41% (95% CI:0.12-0.69), respectively. Among 6 patients who had undergone consolidative SCT, 3 are alive and 3 are dead due to relapsed lymphoma. Of 12 patients who had not received consolidative SCT, five were dead at the time of analysis (Figure 1 E&F).A total of 381 adverse events (AEs) were observed in 49 patients (85%). In general the treatment was well tolerated with dose reduction required in 8 patients (3 due to cytopenias, 1 neutropenia, 1 renal failure, 1 peripheral neuropathy, 2 unknown).In our cohort, we report that 10 patients (17%) had long term continuous response following BV therapy and 5 patients (8.6%) had long term continuous CR (median OS: 56 months; range: 41-64 months) without any additional consolidative therapy. Our results are close to the long term results of pivotal study (Chen et al. Blood 2016) and French study (Perrot et al. Haematologica 2016). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Retrospective Multicenter Analysis of the Safety and Efficacy of Brentuximab Vedotin (BV) As Monotherapy or in Combination with Bendamustine (BV-B) in Relapsed Refractory Classic Hodgkin Lymphoma (cHL) in Argentina

TITLE: A retrospective multicenter analysis of the safety and efficacy of Brentuximab Vedotin (BV) as monotherapy or in combination with Bendamustine (BV-B) in relapsed refractory Classic Hodgkin Lymphoma (cHL) in Argentina.PURPOSE: We performed a retrospective multicenter study in Argentina to collect information on patients (pts) with relapsed refractory cHL treated with BV as monotherapy or with its combination with BV-B. All patients that received either therapy were included with no exclusion criteria. The primary endpoint was response rate and EFS. Toxicity and OS were secondary end points. PATIENTS AND METHODS: Between 8/2011 and 2/2017, 112 pts met inclusion criteria, 93 had complete data and were evaluable for response, among these 71 pts received BV as monotherapy and 22 with BV-B. Median age for all pts was 29 (range 16-73).RESULTS: All 112 pts were evaluable for toxicity. In the group of 78 pts treated with BV 46 (59%) presented at least one adverse events (AE). With 13 (17%) of AE grade III-IV (4 grade IV peripheral neuropathy, 7 grade III-IV infections and 3 grade III neutropenia). In the group of 34 pts treated with BV-B, 17 (50%) had some AE, 11 pts (32%) presented grade III-IV AE: 2 peripheral neuropathy, 1 grade IV infection and 4 (12%) pts with SNC AE (1 seizures, 2 aseptic meningitis and 1 encephalopathy).With a median follow up of 13 months, pts treated with BV had a PFS of 41% and an OS of 75% at 1 yr. The outcome was better for those pts who achieved a CR, with a PFS of 80% and an OS 95%.In a multivariate analysis for obtaining CR after BV, considering: Bulky disease, 2 vs > 2 lines of prior treatment and primary refractory/early relapse vs late relapse, the only significant unfavorable prognostic factors was being primary refractory/first relapse within the first year (P=0.019).For the group of pts with BV-B the PFS was 42% with an OS of 95%, and 62% and 100% for those in CR.CONCLUSIONS: This is the first and only retrospective multicenter trial showing the Argentine experience with Brentuximab. Our findings add to the growing body of evidence supporting the efficacy of Bv as monotherapy and the high ORR and CR of the combination of Bv-B, and warrant a confirmatory randomized trial to re-examine the efficacy and toxicity of this drug combination over BV as monotherapy. [Display omitted] DisclosuresShanley:Gador: Speakers Bureau. Pavlovsky:Janssen: Honoraria, Speakers Bureau. Riveros:Janssen: Consultancy, Speakers Bureau; Raffo: Consultancy, Speakers Bureau; BMS: Speakers Bureau. Pavlovsky:TAKEDA: Speakers Bureau.

Impact of treatment on IL-4, IL-6, IL-10 and sCD25 levels in patients with Hodgkin’s Lymphoma

S222 in other PTCL with different CD30 expression levels. The aim of the study was to investigate the efficacy of BV in patients with relapsed or refractory PTCL. Methods: From March 2011 to January 2014, 74 patients were treated with BV in France in a compassionate patient program for recurrent PTCL. The diagnosis of PTCL was actually confirmed according to the 2008 WHO classification, after local histopathologic review, for 66 patients, including 56 patients with extensive immunohistochemical studies and centralized CD30 immunostaining. The primary end point was best response under BV. Progression free survival (PFS), OS, and safety, were analysed as secondary endpoints. Results: Patients were treated for: systemic ALCL (n1⁄425): ALCL ALK(n1⁄415) and ALCL ALK+ (n1⁄410); systemic PTCL (n1⁄422): PTCL NOS (n1⁄412), adult T-cell leukemia/lymphoma (n1⁄44), enteropathyassociated T-cell lymphoma (n1⁄44), and angioimmunoblastic T-cell lymphoma (n1⁄42); and cutaneous primary lymphoma (n1⁄419), Mycosis Fungoides/Sezary syndrome (n1⁄411) and Cutaneous CD30+ T-cell lymphoproliferative disorders (n1⁄48). CD30 was scored >75%, 10-70% and undetectable ( 75%) have a significant longer PFS (14.1 versus 5.7 months). Median OS was 25.9 months [95% CI 11.9; NR]. Conclusion: In this limited series of patients with different PTCL subtypes treated with BV, the level of expression of CD30 seems to impact outcome with a significantly poorer PFS for cases with a lower level of expression of CD30.

Brentuximab Vedotin (BV) an Effective Treatment for Autologous (ASCT) and/or Allogeneic (alloSCT) Transplant naïve Patients with Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) : A retrospective Single-Institution Study

Background: Patients with R/R HL, failing to achieve a complete remission (CR) or a good partial remission (PR) after conventional dose salvage chemotherapy as well as those having severe comorbidities or advanced age, are generally ineligible for a transplant procedure. Furthermore approximately 50% of the patients able to proceed to ASCT, will eventually relapse and will need effective treatment to proceed to alloSCT. BV is a safe and highly effective treatment in R/R HL after ASCT and 75% objective remissions have been reported . Limited data exist regarding BV in transplant naive R/R HL or in R/R HL after ASCT. The aim of our retrospective study was to assess the efficacy and tolerability of BV in R/R HL patients, treated at a single institution, the Istituto Nazionale Tumori of Milan Italy (INT-MI).Methods: Patients with R/R CD30-positive HL, treated with BV between January 2011 and April 2014 for failure of at least two prior therapies, when ASCT was not considered a treatment option (Group A), or for failure following ASCT (Group B), were included in this retrospective analysis. BV was given at the standard dose of 1.8 mg/kg iv every 21 days. The study protocol was approved by the ethical committee of INT-MI. The primary endpoint of this study was to evaluate efficacy of BV in obtaining FDG-PET remission and in enabling patients to proceed to ASCT or alloSCT. Secondary endpoints included BV toxicity, Progression-free Survival (PFS) and Overall Survival (OS).Results: Sixteen R/R HL patients for Group A (ASCT-ineligible) and 10 patients for Group B (ASCT failures) were identified. Main characteristics at start of BV were as follows: TableCharacteristicsGroup A (n=16)Group B (n=10)Males/Females7/92/8Median age (range) yrs40 (22-72)43 (13-63)B Symptoms54Stage III-IV87Extra ± nodal involvement85³ 3 involved sites63Bulky disease (>7 cm)4 (1 na)2ECOG PS 0/1/27/7/24/4/1 (1 na)Refractory/relapsed after front-line therapy11/57/3Median number prior regimens (range)4 (2-12)4 (3-9)Median time from HL diagnosis to BV therapy start was 19 months (range, 8-330) in Group A and 24 months (range, 16 to 254)in Group B, respectively. A median of 6 BV cycles (range, 3 to 19) were administered. Overall response rate in Group A and B was 87.5% and 60%, respectively; CR was documented in 8 patients (50%) in Group A and 2 patients (20%) in Group B. Best response was reported after a median of 3 cycles (range, 2-9). Three patients in Group A and 1 in group B, achieving a negative PET scan, by continuing BV therapy, had PD and were considered transplant ineligible. BV enabled 3 patients in Group A and 1 patient in Group B, achieving CR , to receive a transplant procedure. Moreover two complete responders in Group A underwent ASCT, although PET scan before transplant documented the reappearance of FDG-avid lesions; they are both alive in CR after 14 and 7 months from ASCT, respectively. Two pts in Group B, achieving a PR, underwent alloSCT and relapsed 6 and 11 months after transplant, respectively. Six patients (23%) had grade 3 or higher adverse events (1 sensory peripheral neuropathy, 5 hematological toxicities), no patient discontinued treatment due to toxicity. After a median follow-up of 15 months (range, 3 to 36) since the first BV cycle, median PFS was 5 months and median OS was still not reached.Conclusions: These data confirm that BV is highly effective in R/R transplant ineligible HL patients, who have generally limited conventional treatment options and a low median OS. BV may overcome chemorefractoriness and enable patients to receive ASCT or allo-SCT, while omitting the significant toxicity of multiagent chemotherapy regimens. DisclosuresViviani:Takeda: Consultant for 40th EBMT Symposium Other.

Brentuximab Vedotin in Combination with Chp in Patients (Pts) with Newly-Diagnosed Cd30+ Peripheral T-Cell Lymphomas (Ptcl): 2-Year Follow-Up

ABSTRACT Aim: PTCL comprises a subset of aggressive non-Hodgkin lymphomas. Outcomes of frontline treatment (tx) are poor, with complete remission (CR) rates of 39–53% (Reimer 2009; D'Amore 2012) and 5-yr overall survival (OS) rates of 12–49%, depending on subtype (Vose 2008). Brentuximab vedotin (ADCETRIS®; BV) has shown clinical activity in a phase 1 trial of BV in sequence with CHOP or in combination with CHP (CHOP without vincristine; A + CHP) in pts with newly-diagnosed PTCL (Fanale, ASH 2013). Methods: This phase 1, open-label study assessed the safety and efficacy of BV administered sequentially with standard-dose CHOP or in combination with CHP for the frontline tx of PTCL (ClinicalTrials.gov NCT01309789). ALK+ systemic anaplastic large cell lymphoma (sALCL) pts must have had IPI score ≥2. Combination tx included a cohort to determine the recommended dose of BV in A + CHP to be evaluated in an expansion cohort (6 cycles q3wk). Responders could receive single-agent BV (1.8 mg/kg q3wk) for up to 10 additional cycles. Updated progression-free survival (PFS) and OS data from combination tx is presented. Results: The median age of pts was 56 yrs (range, 21–82; n=26). Diagnoses included sALCL (n = 19; 16 ALK-), peripheral T-cell lymphoma-NOS (n = 2), angioimmunoblastic T-cell lymphoma (n = 2), adult T-cell leukemia/lymphoma (n = 2), and enteropathy-associated T-cell lymphoma (n = 1). The maximum tolerated dose of BV in A + CHP was not exceeded at 1.8 mg/kg IV, based on 1 DLT (Grade 3 rash). 23 of 26 pts completed 6 cycles of A + CHP. Treatment-emergent adverse events (≥40%) included peripheral sensory neuropathy, nausea, fatigue, alopecia, diarrhea, and dyspnea. At the end of combination tx, the objective response rate was 100% and CR rate was 88%. After a median observation time of 27.1 months, the 2-yr PFS and OS rates were 54% (95% CI 32, 71) and 80% (95% CI 59, 91), respectively. The estimated median PFS was not reached. No pts went on to receive a consolidative stem cell transplant. Conclusions: A + CHP delivered durable remissions in newly-diagnosed PTCL pts, with a 2-yr PFS rate of 54%. A phase 3 study comparing A + CHP to CHOP in the frontline tx of PTCL is underway (ClinicalTrials.gov NCT01777152). Disclosure: M.A. Fanale: Acted as a consultant for: Seattle Genetics, Inc. Honoraria provided by: Seattle Genetics, Inc. Travel expenses provided by: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; S.M. Horwitz: Consultant: Celgene, Seattle Genetics, Inc., Janssen, Takeda International Pharmaceuticals International Co. Research funding/grants: Takeda International Pharmaceuticals International Co., Kiowa Kirin, Allos, Celgene, Infinity, Seattle Genetics, Inc.; A. Forero-Torres: Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Speakers bureau: Seattle Genetics, Inc.; N.L. Bartlett: Acted as a consultant for: Seattle Genetics, Inc. Travel expenses provided by: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; R.H. Advani: Research funding/grants: Seattle Genetics, Inc., Genentech, Takeda Pharmaceuticals International Co., Abbott, Allos, Janssen, Pharmacyclics Consultant: Seattle Genetics, Inc., Genentech, Takeda Pharmaceuticals International Co., Celgene; B. Pro: Acted as a consultant for: Seattle Genetics, Inc. Travel expenses provided by:Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; R.W. Chen: Acted as a consultant for:Seattle Genetics, Inc. Travel expenses provided by:Seattle Genetics, Inc. Research funding/grants provided to the authors institution by:Seattle Genetics, Inc. Speakers bureau: Seattle Genetics, Inc.; A. Davies: Acted as a consultant for: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Honoraria provided by: Takeda Pharmaceuticals International Co.; T. Illidge: Acted as a consultant for: Seattle Genetics, Inc. Takeda Pharmaceuticals International Co. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Honoraria provided by: Takeda Pharmaceuticals International Co.; D. Huebner: Employment: Takeda Pharmaceuticals International Co. Equity ownership (including stock options): Takeda Pharmaceuticals International Co.; D.A. Kennedy: Employment: Seattle Genetics, Inc. Equity ownership (including stock options): Seattle Genetics, Inc.; A.R. Shustov: Acted as a consultant for: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Honoraria provided by: Seattle Genetics, Inc. Speakers bureau: Seattle Genetics, Inc.

Phase II study of bevacizumab (Bv) in combination with paclitaxel-carboplatin (PC) as first-line chemotherapy for nonsquamous (SQ) non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE).

e19021 Background: Vascular endothelial growth factor (VEGF) plays an important role in NSCLC with MPE, but the evidence regarding the efficacy of Bv with PC for treatment of NSCLC with MPE is lacking. Therefore, we prospectively evaluated the efficacy and safety of Bv and PC in non-SQ NSCLC pts. Methods: Chemotherapy-naive non-SQ NSCLC pts with MPE were eligible to participate. Pleurodesis before chemotherapy was not allowed. The treated pts received PC without Bv in the first cycle to prevent Bv-induced delayed wound healing after chest drainage. Subsequently, they received 2–6 cycles of PC with Bv. Patients who completed more than 3 cycles of PC and Bv without disease progression or severe toxicities continued to receive Bv alone as a maintenance therapy. The primary endpoint was overall response, although an increase in MPE was allowed in the first cycle. The plasma and MPE VEGF levels were measured at baseline and the plasma VEGF levels after 3 cycles of chemotherapy. Results: Between September 1, 2010 and June 30, 2012, 23 pts were enrolled. The overall response rate was 60.8%, and the disease control rate was 87.0%. No pts showed complete response, 14 showed partial responses, 6 showed stable disease, 2 showed disease progression, and 1 died in the first cycle. Sixteen pts received maintenance therapy, following a median of 3 cycles. The median progression-free survival period for all pts was 200 days (95% CI, 156–263 days), whereas the median overall survival was 328 days (95% CI, 206–415 days). All pts experienced high levels of hematological toxicities, with most pts experiencing neutropathic toxicities above grade 3. However, none of the pts experienced severe bleeding events. The median baseline MPE VEGF level was 1798.6 (range, 223.4–35,633.4) pg/mL. The plasma VEGF levels showed a significant decrease after 3 chemotherapy cycles (baseline, 513.6 ± 326.4 pg/mL; post-chemotherapy: 25.1 ± 14.1 pg/mL; p < 0.01), regardless of the degree of efficacy. Conclusions: The combination of PC with Bv was confirmed to be effective and reasonably well-tolerated in chemotherapy-naïve non-SQ NSCLC pts with MPE. Clinical trial information: UMIN000005284.

648 - Efficacy and Safety of Bevacizumab Combined with Chemotherapy in Daily Practice in 765 French Patients with MCRC: The Concert Cohort at a Maximum of 24 Months Follow-Up

ABSTRACT Background CONCERT is a prospective, non-interventional study assessing the first use of bevacizumab (Bv) combined with standard chemotherapy (CT) -all lines, in daily practice in mCRC patients (pts) included in 2008/2009. We present results at 24 months including overall survival (OS). Results at 12 months were presented earlier (Poster # 249 - WCGIC 2011). Method Pts with mCRC initiating Bv + CT, doses and schedules at investigator's discretion, were followed at 3, 6, 9, 12, 18, 24 and 36 months. Pts characteristics, safety and efficacy of Bv + CT were assessed. Targeted adverse effects (AEs) and serious/unexpected AEs were collected. Results On a total of 725 evaluable pts with mCRC, initiating Bv + CT, 435 (60%) were men, median age 66 years (min–max: 25-88), ECOG score 0-1 (90%). After a maximum of 24 months of follow-up per patient, median progression-free survival (primary endpoint) was 10.4 months [9.6;11.7], 8.6 [7.1;9.5] and 6.3 [5.6;8.9] in 1st, 2nd and 3rd line or more, respectively. Median OS was 25.4 [21.2;-], 19.0 [15.4; 22.3] and 14.3 [11.6; 20.4] in 1st, 2nd and 3rd line or more, respectively. In 1st line, progression-free survival was 10.4 [9.3; 11.7] with irinotecan-based CT and 11.8 months [9.9;15.2] with oxaliplatin-based CT. Bv median treatment duration was 7,5 months. AEs were reported in 56.2%, 68.1% and 51.7% of pts in 1st, 2nd and 3rd line or more. Grade 3/4 AEs were reported in 10.4% of pts overall. Main grade 3/4 targeted AEs were neutropenia (3.0%), venous thromboembolic events (1.8%) and hypertension (1.3%) and 6.8% of pts were newly treated for hypertension at M3. Most AEs occurred during the first 12 months. Deaths were reported in 39.9% of pts, 51.4% and 56.9% in 1st, 2nd and 3rd line or more, respectively mainly for disease progression (87.8%). During follow-up, 33.8% of pts had at least one surgery, mainly of the liver (40.7% of all surgeries). Conclusions Efficacy and safety outcomes after 24 months of follow-up in mCRC pts treated confirm the appropriate use of bevacizumab in daily practice in France as they are consistent with published reports of international non-interventional studies and registry (BRiTE, Tree, Beat). Disclosure J. Bennouna: Honoraries : Roche, Amgen, Sanofi-Aventis. M. Ducreux: Consultant : Roche, Merck Serono Honoraries : Roche, Merck Serono, Amgen, Bayer, Fresenus, Pfizer, Sanofi Clinical research project: Pfizer, Chugai, Merck Serono. T. Andre: Consultant : Roche Honoraries : Amgen, Merck, Sanofi. H. Senellart: Honoraries : Roche. B. Commenges: Employment : Roche. All other authors have declared no conflicts of interest.

Final safety results of BO17704 (AVAiL): A phase III randomized study of first-line bevacizumab (Bv) and cisplatin/gemcitabine (CG) in patients (pts) with advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC)

8039 Background: AVAiL, an international placebo-controlled phase III trial, showed that Bv-based therapy significantly improved PFS and response rate in patients with advanced/recurrent NSCLC. This report summarizes overall safety findings from AVAiL. Methods: AVAiL randomized 1,043 patients with untreated locally advanced, metastatic or recurrent non-squamous NSCLC to C 80mg/m2 (d1) and G 1,250mg/m2 (d1 and d8) q3w for up to 6 cycles plus either Bv 7.5mg/kg q3w (n=331 with safety data), Bv 15mg/kg q3w (n=329) or placebo (n=326). Bv/placebo was administered until disease progression. Primary endpoint was PFS; secondary endpoints included OS, response rate, and safety. Safety was measured using NCI-CTC version 3.0 criteria for adverse events (AEs). Results: At final analysis, the median/maximum duration of Bv therapy was 4.9/28.5 mo (Bv 7.5) and 4.3/23.4 mo (Bv 15). The most common AEs overall were hematological and gastrointestinal (GI), and occurred in similar proportions of pts in the Bv and placebo arms. Grade ≥3 AEs occurred in 80%, 83%, and 77% of pts in the Bv 7.5, Bv 15 and placebo arms, respectively. The most common grade ≥3 adverse events were hematological, mainly neutropenia and thrombocytopenia. Neutropenia was reported in 43% (Bv 7.5), 40% (Bv 15) and 34% (placebo) of pts. Grade ≥3 AEs of special interest included hypertension (7%, 9% and 2%), proteinuria (2%, 3% and 0%), bleeding (4%, 5% and 2%) and hemoptysis (0.5%, 1.2% and 1.3%). The incidence of grade 5 hemoptysis was low (0.9%, 0.9% and 0% of pts, respectively). The incidence of GI perforations (<1%), thromboembolic events (≤8%), CHF (≤1%) and wound healing complications (<1%) was low and similar between treatment arms. The incidence of serious AEs was 39%, 45% and 36% in the Bv 7.5, Bv 15 and placebo arms, respectively. No new safety signals were reported. Conclusions: After E4599, AVAiL further demonstrated the efficacy of Bv in combination with platinum-based chemotherapy in the treatment of advanced NSCLC. Final safety data confirm the well established and manageable safety profile of Bv-based therapy in pts with advanced NSCLC. [Table: see text]