First-line Bevacizumab-based Therapy Research Articles

Existing anti-angiogenic therapeutic strategies for patients with metastatic colorectal cancer progressing following first-line bevacizumab-based therapy.

Continuous inhibition of angiogenesis beyond progression is an emerging treatment concept in the management of metastatic colorectal cancer patients with prior bevacizumab exposure. Treatment options include the continuation or reintroduction of bevacizumab during the second-line chemotherapy or switching to a different antiangiogenic monoclonal antibody such as aflibercept or ramucirumab. In the selection of treatment, patient-based factors such as performance status, age, tumor burden, and tolerance and sensitivity to the first-line bevacizumab-based therapy, as well as treatment-related factors such as toxicity, efficacy, and cost, should be taken into consideration.

Long-term response to first-line bevacizumab-based therapy in patients with metastatic breast cancer: results of the observational "LORENA" study.

BackgroundRandomized controlled trials of the first-line combination of bevacizumab and chemotherapy in patients with metastatic breast cancer (MBC) have shown improvements in tumor response and progression-free survival (PFS).ObjectiveThe aim of this ambispective, observational study (LORENA) was to describe the clinical characteristics of long-term responders to bevacizumab-based therapy.Patients and methodsThis study consisted of a retrospective and a prospective phase. During the retrospective phase, patients with HER2-negative MBC who were treated with bevacizumab-based first-line therapy were included. During the prospective phase, patients with PFS of ≥12 months were treated according to routine clinical practice procedures. Overall survival (OS) and PFS were estimated using the Kaplan–Meier method. Univariate and multivariate analyses of prognostic factors were performed.ResultsIn total, 148 women were included (median age: 50 years; range: 29–81 years). The mean duration of exposure to bevacizumab was 18 months. The majority of patients experienced objective response (complete: 23%; partial: 57%). Median PFS was 22.7 months and median OS was 58.2 months. In multivariate analyses, patients receiving maintenance hormonal therapy (MHT) had longer PFS (P=0.002; hazard ratio [HR] =1.8) and OS (P=0.009; HR=2.0), while patients not previously treated with taxanes had longer OS (P<0.0001; HR =3.3). No unexpected adverse events were observed.ConclusionThe results of this study suggest, that among long-term responders, first-line bevacizumab-based therapy is more effective in patients who had not been previously treated with taxanes, and that MHT provides additional therapeutic benefits by extending PFS and OS.

Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients

IntroductionThe optimal treatment strategy for RAS wild type (WT) mCRC is controversial. Our phase III study investigated the effect of introducing earlier (second-line) or later (third-line) cetuximab in patients progressed after FOLFIRI/bevacizumab first-line. Patients and methodsmCRC patients progressing after FOLFIRI/bevacizumab first-line were randomised to receive second-line irinotecan/cetuximab followed by third-line FOLFOX-4 (arm A) or the reverse sequence (arm B). Primary end-point was progression-free survival (PFS). ResultsAbout 54 and 56 patients were randomised in arm A and in arm B, respectively. After a median follow-up of 37.5 months, 100 PFS events were recorded. Median PFS was 9.9 months in arm A and 11.3 months in arm B (Hazard ratio [HR] 1.04, 95% confidence interval [CI]: 0.69–1.56, p = 0.854), while median overall survival was 12.3 months in arm A and 18.6 months in arm B (HR 0.84, 95% CI: 0.55–1.28; p = 0.411). No overall difference in side-effects were observed between the two treatment arms. ConclusionsThis trial did not meet the primary end-point (PFS). Like other preclinical and clinical evidences, our study seems to suggest a reduced activity of cetuximab after a first-line bevacizumab-based therapy.

Long-term responders to first-line bevacizumab-based therapy in metastatic breast cancer (MBC) patients: Results of the observational study LORENA.

e12563 Background: Randomized controlled trials in MBC patients evaluating bevacizumab as first-line treatment showed improvements in tumor response and progression-free survival (PFS) when added to chemotherapy. The aim of the LORENA study was to describe the clinical features, prognosis factors and safety of bevacizumab and chemotherapy treatment for MBC in routine practice. Methods: Observational, multicentre, ambispective study conducted in Spain. The study had a retrospective and a prospective phase. Data were obtained from March 2012 to October 2013. In the retrospective phase, eligible patients were women with metastatic or locally-advanced breast cancer, treated with bevacizumab as a first-line therapy, and progression-free survival for ≥ 12 months. In the prospective phase, patients were followed-up and assessed as per routine clinical practice. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed. Results: 148 women from 38 centers were included. The mean age was 52 (±11) years. Bone, lung and liver were the most frequent metastasis sites. 138 patients were HER2-neg. on diagnosis (data unknown in 10 patients). The mean exposure to bevacizumab was 18 (±11) months. Most patients had objective response, 23% complete response, and 57% partial response. Median OS was 58.2 months and median PFS was 22.7 months. In multivariate analyses, OS was higher in patients with hormonal maintenance therapy (HMT) (p = 0.009; HR = 2.0) and in patients not treated with taxanes before the metastatic diagnosis (p &lt; 0.0001; HR = 3.3); also, PFS was higher in patients with HMT (p = 0.002; HR = 1.8). No adverse events were observed other than those reported previously. Conclusions: Outcomes of OS and PFS suggest a benefit from bevacizumab maintained therapy. HMT was a PFS prognosis factor. HMT and not having been treated with taxanes before the metastatic diagnosis were two independent OS prognosis factors. Our results could provide further evidence supporting the use of bevacizumab as maintenance therapy for MBC patients.

Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy.

First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9months. Median overall survival and PFS were 30.7 and 15.1months, respectively. The overall response rate was 83%. Weight loss ≤5%, ECOG PS=0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.

Angiogenesis- and Hypoxia-Associated Proteins as Early Indicators of the Outcome in Patients with Metastatic Breast Cancer Given First-Line Bevacizumab-Based Therapy.

We examined whether pretreatment levels of angiogenesis- or hypoxia-related proteins and their changes after one cycle of first-line bevacizumab-based therapy were associated with response, PFS, or OS in patients with metastatic breast cancer. We included 181 patients enrolled in the phase II ATX trial evaluating first-line paclitaxel and bevacizumab without or with capecitabine (NTR1348). Plasma samples were analyzed for VEGF-A, soluble VEGFR2 (sVEGFR2), angiopoietin 2 (ANG2), soluble TIE2 (sTIE2), IL6, IL8, and carbonic anhydrase 9 (CA9). Baseline serum CA15-3 was documented. HR was adjusted for confounding factors. Where appropriate, an optimal cut-off value defining a high and a low group was determined with Martingale residuals. At baseline, multiple proteins were significantly associated with PFS (ANG2, IL6, IL8, CA9, CA15-3) and OS (ANG2, sTIE2, IL6, IL8, CA9, CA15-3). After one cycle, VEGF-A, ANG2, sTIE2, and IL8 significantly decreased, while sVEGFR2 and CA9 significantly increased. The relative change in sVEGFR2 (P= 0.01) and IL8 (P= 0.001) was associated with response. Defining optimal cut-off, patients with a high CA9 rise (>2.9%) had better PFS (HR 0.45) and OS (HR 0.54) than those with low/no rise. Multiple angiogenesis- or hypoxia-related proteins were prognostic for PFS and OS. Molecular agents targeting these proteins might be beneficial in patients with high levels. Changes in IL8 or sVEGFR2 levels at second cycle appear predictive for response. Changes in CA9 levels during bevacizumab-based therapy for prediction of PFS and OS merit further study.

Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer.

Carcinoembryonic antigen (CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor angiogenesis. This study aimed to evaluate baseline CEA serum levels to predict bevacizumab-based therapy effect and survival in patients with metastatic colorectal cancer (mCRC). Two hundred and ninety eight mCRC patients receiving chemotherapy plus either bevacizumab or cetuximab were analyzed in a retrospective study. Disease control (DC), progression-free survival (PFS), and overall survival were assessed and related to pretreatment CEA serum levels. Patients with baseline CEA serum levels below the statistical median of 26.8 ng/mL (group I) were compared with patients with higher CEA levels (group II). The cetuximab-based treatment cohort was analyzed for specificity assessment of CEA to predict the anti-vascular endothelial growth factor effect in mCRC. Baseline CEA serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (disease control rate, 84% vs 60%), inversely correlated with median PFS leading to a median PFS benefit of 2.1 months for patients in group I when compared with group II, as well as inversely correlated with median overall survival (37.5 months vs 21.4 months). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CEA serum levels was found. As expected, baseline CEA levels were prognostic for mCRC. These data give first evidence that baseline serum CEA levels might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy in patients with mCRC.Previously, we found that CEA induces angiogenesis independent of VEGF. The data presented here now give first evidence that baseline serum CEA levels in patients might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy for metastatic colorectal cancer.

Impact of pre-angiogenic factors on the treatment effect of bevacizumab in patients with metastatic colorectal cancer

Endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) play a major role in tumor growth and metastasis. Our aim was to determine whether there is any association between these endothelial parameters and tumor markers with the clinical outcome of bevacizumab-treated metastatic colorectal cancer (mCRC) patients in terms of response and survival. Pretreatment serum levels of ET-1, ADMA, carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9 were measured in 36 chemotherapy-naive mCRC patients treated with first-line bevacizumab-based therapy. Additionally, after first cycle of treatment, serum levels of these parameters were reanalyzed. Lower baseline serum ET-1 and ADMA levels were observed in patients responding to bevacizumab-based treatment (respectively, p = 0.037, p = 0.034). Median progression-free survival (PFS) (11 vs. 6 months, p = 0.012) and overall survival (OS) (28 vs 9 months; p = 0.007) were significantly shorter in patients with high pretreatment ET-1 levels. There was a significant decrease in ET-1 and CEA levels after first treatment (p = 0.020, p = 0.012), while ADMA and CA 19-9 levels were not significantly changed. Patients with decreased posttreatment ET-1 levels were shown to have inferior PFS (6 vs 11 months, p = 0.022), but no statistically significant difference was shown with respect to OS (p = 0.141). The effect of bevacizumab on endothelin axis including the biologic basis of decreasing ET-1 levels due to bevacizumab treatment and its association with inferior outcome has to be clarified in prospective trials.

Long-term responders to first-line bevacizumab-based therapy among patients (pts) with HER2-negative metastatic breast cancer (MBC): Retrospective results of an ambispective observational study.

e12558 Background: LORENA is an ambispective observational study evaluating B-based therapy in a real world setting which purpose is to assess clinical features, treatments and prognosis of HER2-negative MBC pts with ≥12 months (mo.) of PFS to 1st-line B-based chemotherapy (CT). Methods: Pts with MBC receiving 1st-line CT and B are enrolled. No prespecified schedules, doses or assessments. Data since the introduction of the treatment with B were collected at inclusion (retrospective phase), and prospectively at 18 mo. after enrollment for the patients alive at the time of inclusion, including B-targeted adverse events (AEs). Relevant baseline and on-study variables were analyzed by Cox model to identify independent effects on PFS. Results: By Jan 2013, complete retrospective data were available for 84 pts, 33 (39.3%) of them having stage III-IV at diagnosis. Median age, 50 years (r: 29–77); age ≥65 years, 13%; triple negative, 20.2%; bone/liver/lung metastases (%), 55/27/40; ≥2 metastases sites: 46.4%; ECOG status 0-1: 91.7%, ≥2: 5.9%, UK: 2.3%. 67% of pts have received prior (neo)adjuvant CT, with 56 and 30% of them with anthracyclines and taxanes, respectively. The objective response was 78%, including complete responses in 23%. A further 22% had stable disease. Median duration of B-based therapy was 12.4 mo. PFS events had been recorded in 44% of pts. Median PFS: 19.5 mo. (95%CI: 15.6-23.2). Cox proportional hazard multivariate regression model showed that B-based therapy ≥15 vs &lt;15 mo was associated with improved PFS (26.5 vs 14.0 mo, p= 0.009; HR 0.40 [95%CI: 0.19-0.81]). The most common grade ≥3 B-related AEs were: Hypertension 9.5%, proteinuria 3.5%, bleeding 3.5%, and thromboembolic events 1.1%. No B-related death was reported. Conclusions: Outcomes in routine oncology practice for LORENA patients are consistent with those from prospective trials of 1st-line B-containing therapy and ATHENA study. These results suggest a benefit from a maintained VEGF suppression and that B continuation either as a single agent or combined with CT, until disease progression is recommended. Follow-up is ongoing.

Predictive value of baseline CD66e/CEA serum levels on efficacy of bevacizumab-based treatment in advanced colorectal cancer.

388 Background: CD66e (Carcinoembryonic antigen, CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor-angiogenesis. This study aimed to evaluate baseline CD66e serum levels as response predictor to bevacizumab-based therapies in patients with metastatic colorectal cancer (mCRC). Methods: 298 patients with mCRC and first-line treatment were analyzed. 169 mCRC received bevacizumab plus chemotherapy and 129 patients with mCRC treated with cetuximab (KRAS w.t.) and identical chemotherapy (FOLFOX6 or FOLFIRI). Disease control (DC), progression-free survival (PFS) as well as overall survival (OS) were assessed and related to baseline CD66e-serum levels. Patients with basal CD66e-serum levels below the statistical median of 26.8 ng/ml (group I) were compared with patients with higher CD66e levels (group II). Results: Baseline CD66e serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (chi square i&lt;0.005: OR=0.579, 95% C.I. 0.422, 0.795; p&lt;0.001), inversely correlated with median PFS leading to a median PFS benefit of 2.1 month for patients in group I when compared with group II (p&lt;0.05), as well as inversely correlated with median OS (37.5 month vs. 21.4 month, p&lt;0.05). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CD66e serum levels was found (p&gt;0.05). Conclusions: These data give first evidence of CD66e as a predictive biomarker for the efficacy of first-line bevacizumab-based therapy in patients with mCRC.

First-Line Bevacizumab-Based Therapy in Advanced Non-Squamous Non-Small-Cell Lung Cancer

First-line bevacizumab-based therapy has been shown to improve outcomes in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The recent international phase IV SAiL study (a Study of Avastin [bevacizumab] in combination with platinum-containing chemotherapy in patients with advanced or recurrent non-squamous cell Lung cancer) evaluated the safety and efficacy of bevacizumab combined with standard chemotherapy regimens in routine clinical practice. Here we report the results of a subanalysis of baseline characteristics and efficacy data for Italian patients enrolled in SAiL. In the SAiL study, patients with untreated locally advanced, metastatic or recurrent non-squamous NSCLC received bevacizumab (7.5 or 15 mg/kg) every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Efficacy was assessed in terms of time to disease progression (TTP) and overall survival (OS). The Italian intent-to-treat population comprised 215 patients from a SAiL population of 2212 patients. At baseline, Italian patients tended to have less advanced disease than the overall population. Thus, the proportion of patients at enrollment with tumour stage IIIb and IV was 23.7 and 76.3 %, respectively, for the Italian population versus 19.7 and 80.3 % for the whole SAiL population. In addition, a higher proportion of Italian patients had an Eastern Cooperative Oncology Group performance status of 0 (72.6 vs. 37.2 %) and the prevalence of co-morbid conditions was lower in Italian patients (59.5 % of Italian patients reported a co-morbid condition and 60.0 % were receiving non-oncological treatment compared with 73.3 and 73.4 %, respectively, of SAiL patients overall). The mean exposures to bevacizumab and to chemotherapy were comparable between the Italian patient group and overall patient population, although cisplatin doublets were more commonly employed in Italian patients whereas carboplatin doublets were more commonly employed in the overall SAiL population. The median TTP and OS times for Italian and SAiL populations were comparable (TTP, 7.8 months vs. 7.8 months; OS, 14.8 months vs. 14.6 months). The results of this subanalysis of the SAiL study of bevacizumab treatment in routine clinical practice suggest that Italian oncologists tend to prescribe bevacizumab to a selected population of patients with less advanced disease than is the case in the overall population. Nevertheless, the first-line use of bevacizumab in combination with chemotherapy offers clinical benefits to Italian patients with advanced or recurrent non-squamous NSCLC.

Pre-treatment lactate dehydrogenase levels as predictor of efficacy of first-line bevacizumab-based therapy in metastatic colorectal cancer patients

Background:Lactate dehydrogenase (LDH) represents a predictive factor in colorectal cancer patients treated with the angiogenesis inhibitor PTK/ZK. We explored the role of pre-treatment LDH serum levels in colorectal cancer patients receiving first-line bevacizumab.Methods:Metastatic colorectal cancer treated with first-line bevacizumab was eligible. A control group including all consecutive patients treated with chemotherapy alone was also considered. Pre-treatment LDH serum levels were collected for all cases.Results:Median progression-free survival (PFS) in the control group for patients with high and low LDH levels was 4.2 and 8 months, respectively (P=0.0003). Median overall survival (OS) was 19.6 and 34.9 months for patients with high and low LDH levels, respectively (P=0.0014). In the bevacizumab group, partial responses were seen in 14 (58%) high-LDH and 8 (14%) low-LDH patients (P=0.0243), respectively, median PFS was 7.3 and 8.5 months, respectively (P=0.2), and median OS was 22 and 26.6 months, respectively (P=0.7).Conclusion:High LDH levels correlated with worse prognosis. Bevacizumab seemed capable of improving clinical outcome in this specific group of patients who usually present with an adverse natural history. The improved response rate also suggests a role for LDH as a predictive marker.

Evaluation of efficacy and safety of bevacizumab combined with chemotherapy for Chinese patients with advanced non-small cell lung cancer

背景与目的SAiL（MO19390）研究是一项开放性、国际多中心、单组的临床试验，旨在评价一线使用贝伐珠单抗为基础的治疗在临床上的安全性及疗效。本文25例患者来自本研究中心入组SAiL试验的患者。方法2007年8月-2008年2月在北京协和医院治疗的25例晚期非鳞非小细胞肺癌（non-squamous non-small cell lung cancer, NSNSCLC）患者，接受贝伐珠单抗联合紫杉醇/卡铂治疗，贝伐珠单抗剂量15 mg/kg。评价不良反应、客观有效率（objective response rate, ORR）、中位疾病进展时间（time to progression, TTP）和总生存期（overall survival, OS）。结果最多见的不良反应为脱发、外周神经病变、皮疹、蛋白尿、恶心/呕吐、乏力、肌肉酸痛、鼻粘膜出血和高血压。17例（68%）评估为部分缓解（partial remission, PR），7例（28%）评估为疾病稳定（stable disease, SD），1例（4%）评估为疾病进展（progressive disease, PD），中位TTP为11.2个月，中位OS为19.3个月。结论中国晚期NSNSCLC患者接受贝伐珠单抗治疗的耐受性好，可明显延长TTP和OS。

Safety and Efficacy of First-Line Bevacizumab Plus Chemotherapy in Elderly Patients with Advanced or Recurrent Nonsquamous Non-small Cell Lung Cancer: Safety of Avastin in Lung trial (MO19390)

Safety of Avastin in Lung (MO19390) was an international, open-label, single-arm study, which assessed the safety and efficacy of first-line bevacizumab (Avastin®) in combination with standard chemotherapy in patients (n = 2212) with advanced or recurrent non-small cell lung cancer (NSCLC). A preplanned subgroup analysis was performed to examine these outcomes in elderly patients older than 65 years. Eligible patients with nonsquamous NSCLC received up to six cycles of bevacizumab (7.5 or 15 mg/kg) plus any standard of care chemotherapy. Patients who did not experience disease progression after induction therapy continued bevacizumab therapy until disease progression or unacceptable toxicity. The primary end point was safety; secondary end points included time to disease progression (TTP) and overall survival (OS). Data were evaluated for 623 patients older than 65 years (mean age 70.6). The majority were Whites (86.2%) with stage IV disease (79.7%) and had adenocarcinoma (83.5%). The incidence of adverse events (AEs) of special interest was similar for elderly and younger patients (any grade bleeding 38.2% versus 38.3%; any grade hypertension 33.1% versus 30.6%; any grade proteinuria 33.4% versus 29.3%). Most AEs were grade less than or equal to 2. Serious AEs were reported in 45.3 and 34.7% of elderly and younger patients, respectively. Median OS was similar in elderly and younger patients (14.6 months in both age groups), as were TTP (8.2 versus 7.6 months), response rate (49.3% versus 52.4%), and disease control rate (89.3% versus 88.4%). Similar results were seen in a post hoc comparison of the older than 70 years and 70 years or younger subgroups: TTP was 8.6 months versus 7.7 months, respectively; OS was 14.6 months in both subgroups; response rate was 49% and 52%, respectively; incidence of AEs of special interest was comparable. Patients older than 65 years with nonsquamous NSCLC derive a similar clinical benefit from first-line bevacizumab-based therapy as their younger counterparts and do not experience increased toxicity.

Clinical outcomes for special populations of patients treated with first-line bevacizumab-based therapy in an observational study (AVVA).

e18033 Background: More than 50% of cases of advanced NSCLC are diagnosed in patients (pts) older than 65 years. Furthermore, the majority of pts with NSCLC present at the time of the diagnosis one or more comorbidities. Both subgroups are often under-represented in clinical trials based on perceptions that they do not wish for and/or cannot tolerate active systemic therapy. Methods: AVVA is a multicenter, observational study in pts with advanced NSCLC (stage IIIB noncandidates for radiotherapy or IV) treated with first-line bevacizumab-based regimen. A subanalysis according to age ≥65 years and ≥1 comorbid condition was performed. Preliminary results are presented. Results: A total of 148 pts were evaluated. Median age 57.5 (50-64) years; male 64%; tumor histology: 77% adenocarcinoma, 14% large-cell carcinoma; disease stage IV/IIIB 93%/7%; ECOG 0/1/≥2 37%/56%/7%. 24% of pts were ≥65 years and 64% presented ≥1 comorbid condition at baseline, being the more frequent HTN (19%), dyslipidemia (16%), DM (12%), CVD (7%) and COPD (6%). Commonly used first-line chemotherapy (CT) regimens in combination with bevacizumab were carboplatin doublets in 71% of pts and cisplatin doublets in 26% for a median of 6 cycles. Treatment characteristics and outcomes are specified in the table. The main ≥grade 3 toxicity was DVT in 2.7% of pts. The incidence of ≥ grade 3 AEs of special interest were: haemoptysis <1%, proteinuria <1%, HTN 0%, thromboembolism <1%. DVT (2%) was the only ≥ grade 3 AE reported in elderly pts. In pts with ≥1 comorbidity, DVT (3%), neutropenia (1%) and infection (1%) were the only ≥ grade 3 AEs reported. Conclusions: First-line bevacizumab-based therapy was effective and safe in older pts and pts with at least one comorbid condition. No new safety signals have been indentified and efficacy results match with previously reported data. All patients (n=148) Age ≥65 (n=35) ≥1 comorbid condition (n=95) CT regimen (%) Carboplatin doublets Cisplatin doublets 71 26 68 26 73 25 Median no. of CT cycles 6 6 6 Median no. of bevacizumab cycles 8 6 8 Disease control rate (%) CR PR SD 85.0 1.3 51.3 32.4 85.6 2.9 51.4 31.4 84.1 2.1 52.6 29.5 PFS, months (95% CI) 7.6 (7.2-8.0) 6.6 (5.0-8.2) 7.4 (6.3-8.2)

Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study

Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB-IV); an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7.5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906. At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade > or = 3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily interrupted after 28 (2%) of 1347 bleeding events and 72 (7%) of 1025 hypertension events, and permanently discontinued after 110 (8%) bleeding events and 40 (4%) hypertension events. No new safety signals were reported. Our results confirm the manageable safety profile of first-line bevacizumab in combination with various standard chemotherapy regimens for treatment of advanced non-squamous NSCLC. F Hoffmann-La Roche Ltd.

9168 Safety and efficacy of first-line bevacizumab-based therapy in advanced non-small cell lung cancer (NSCLC): results of the SAiL study (MO19390)

9168 Safety and efficacy of first-line bevacizumab-based therapy in advanced non-small cell lung cancer (NSCLC): results of the SAiL study (MO19390)

Safety of first-line bevacizumab-based therapy with concomitant cardiovascular or anticoagulation medication in advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) in MO19390 (SAiL)

8049 Background: Bevacizumab (Bev) based therapy prolongs survival of NSCLC patients beyond 1 year. MO19390 (SAiL) is an open-label study assessing the safety of Bev with a wide range of standard f...