Safety Of Bevacizumab In Combination Research Articles

Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease.

Simple SummaryIn patients with inflammatory bowel disease, chronic inflammation is a risk factor for the development of digestive and nondigestive cancers. The treatment, as in patients without inflammatory bowel disease, is a combination of chemotherapy and targeted treatments, such as bevacizumab and more recently, immunotherapy. It is generally believed that the use of bevacizumab and chemotherapy could increase toxicity and lead to adverse events in this population. This study aims to evaluate the safety and efficacy of the combination of bevacizumab and chemotherapy in patients with quiescent or moderately active inflammatory bowel disease in various forms of cancer and by increasing the quality of patient care in this subgroup.Background: The safety of bevacizumab in combination with chemotherapy in patients with inflammatory bowel disease (IBD) and digestive and nondigestive cancers is poorly documented. Methods: We retrospectively evaluated patient records of all adult cancer patients with IBD at our institution from April 2007 to May 2016 with an update in November 2019. Results: Twenty-seven patients with a history of IBD (Crohn’s disease, n = 22; ulcerative colitis, n = 5) who were treated with bevacizumab and chemotherapy for metastatic solid tumors were identified. At the time of advanced cancer diagnosis, 18 patients had quiescent IBD, whereas 9 patients had moderately active IBD. Among those with moderately active IBD, five had received corticosteroids less than six months prior to cancer diagnosis and one had received infliximab. The treated cancers were colorectal cancer (n = 13), small bowel cancer (n = 4), non-small cell lung cancer (n = 3), breast cancer (n = 3), and other cancers (n = 4). Patients received bevacizumab in combination with chemotherapy and/or as maintenance for a median of 6.7 months. Grade 2 or higher bevacizumab-related complications were proteinuria in two patients and hypertension, diarrhea, rectal bleeding, and intestinal perforation in one patient each. No clinical IBD flares were observed during bevacizumab treatment. Conclusion: Bevacizumab combined with chemotherapy is safe in cancer patients with moderately active or quiescent IBD.

Bevacizumab, carboplatin, and paclitaxel in the first line treatment of advanced ovarian cancer patients: the phase IV MITO-16A/MaNGO-OV2A study

ObjectiveTo explore the clinical and biological prognostic factors for advanced ovarian cancer patients receiving first-line treatment with carboplatin, paclitaxel, and bevacizumab.MethodsA multicenter, phase IV, single arm trial was performed. Patients...

Bevacizumab in Combination with Pemetrexed and Platinum Significantly Improved the Clinical Outcome of Patients with Advanced Adenocarcinoma NSCLC and Brain Metastases.

BackgroundThe study aims to evaluate the clinical efficacy and safety of bevacizumab in combination with the first-line pemetrexed-platinum (PP) in patients with advanced adenocarcinoma non-small-cell lung cancer (NSCLC) and brain metastases.MethodsThe clinical data of patients with adenocarcinoma NSCLC and symptomatic or asymptomatic brain metastases were collected in our study. The basic chemotherapy regimen was pemetrexed-platinum (PP). According to whether combined with bevacizumab (B) or not, all enrolled patients were assigned to the B+PP group or the PP alone group.ResultsA total of 71 patients were enrolled in the current study. Twenty-six patients were allocated to the B+PP group and 45 were allocated to the PP group. Overall response rates (ORRs), disease control rates (DCRs) of the thoracic tumors and intracranial metastases and overall survival (OS) were not significantly different between the 2 groups. However, progression-free survival (PFS) and intracranial PFS (iPFS) were significantly prolonged in the B+PP group compared with the PP group. The median PFS was 9.2 and 8.2 months, and the 1-year PFS rates were 47.1% and 15.9%, respectively, in the 2 groups (P=0.029). And, the median iPFS were 24.3 and 10.9 months, and the 1-year iPFS rates were 80.1% and 40.1%, respectively, in the 2 groups (P=0.008). Univariate and multivariate analyses suggested that maintenance therapy and bevacizumab therapy were independent favorable prognostic factors of PFS and iPFS.ConclusionThe addition of bevacizumab to the first-line pemetrexed and platinum significantly improved clinical outcomes of patients with advanced adenocarcinoma NSCLC and brain metastases.

AVAiLABLE NIS \u2013 AVASTIN\xae in lung cancer treatment in routine oncology practice in Germany

BackgroundBevacizumab (Avastin®), a recombinant humanized monoclonal antibody, in combination with platinum-doublet chemotherapy has become a routine treatment for advanced non-small-cell lung cancer (NSCLC). The post-authorization, non-interventional study ‘AVAiLABLE’ assessed the effectiveness and safety of bevacizumab combined with chemotherapy as first-line treatment.MethodsNine hundred and eighty-seven adult patients (mean age 61.5 years, 59.8% male) with non-resectable advanced, metastatic or recurrent, predominantly non-squamous NSCLC were evaluated at 185 sites across Germany. 72.8% of the patients had stage IV disease at start of observation, 90.1% had histologically confirmed adenocarcinoma and 80.8% met the bevacizumab label ‘NSCLC other than predominantly squamous cell histology’. According to bevacizumab label, chemotherapy plus bevacizumab was recommended, followed by bevacizumab maintenance therapy. Effectiveness endpoints included response rates and progression-free survival (PFS); safety endpoints comprised adverse drug reactions (ADRs). Patients were followed until progression or intolerable toxicity. Data were evaluated by descriptive statistical methods.ResultsMedian PFS was 7.4 months (95% CI: 7.1; 8.4), overall response rate (ORR) 45.6% and disease control rate (DCR) 75%. The majority of patients (72.7%) achieved partial response or stable disease. Complete response was reached by 2.3%. 33.6% of patients experienced an ADR of grade ≥ 3. Bevacizumab-related ADRs of grade ≥ 3 occurred in 5.7% of patients, with the highest incidence for leukopenia, neutropenia, and hypertension.ConclusionsResults of the non-interventional study ‘AVAiLABLE’ confirmed the effectiveness and safety of bevacizumab in combination with platinum-based chemotherapy as first-line treatment for advanced NSCLC in accordance with previous studies. No new safety signals were identified. Maintenance therapy with bevacizumab was well tolerated and safe even over extended periods (> 20 cycles).Trial registrationClinicalTrials.gov Identifier: NCT02596958; registered on 4 November 2015.

An open-label, randomized, phase II trial evaluating the efficacy and safety of standard of care with or without bevacizumab in platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer patients previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer: rationale, design, and methods of the Japanese Gynecologic Oncology Group study JGOG3023

BackgroundWe present the study rationale and design of the JGOG3023 study, an open-label, parallel-arm, randomized, phase II trial that aimed to assess the efficacy and safety of chemotherapy with or without bevacizumab in patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer. We hypothesize that patients treated with a combination of single-agent chemotherapy and bevacizumab will show improved progression-free survival (PFS) compared with those treated with single-agent chemotherapy alone, in the setting beyond disease progression following prior bevacizumab treatment.Methods/designA total of 106 patients who have recurrence or progression of ovarian cancer, while receiving chemotherapy or within 6 months after the final dose of platinum, after completing at least three cycles of bevacizumab plus platinum chemotherapy will be randomized in a 1:1 ratio to treatment with single-agent chemotherapy or single-agent chemotherapy combined with bevacizumab. For chemotherapy, one of the following four drugs will be chosen by an investigator: pegylated liposomal doxorubicin, topotecan, paclitaxel, or gemcitabine. The primary endpoint is investigator-assessed PFS. The secondary endpoints are overall survival, objective response rate, number of paracentesis, and response rate by CA125. Safety will be evaluated by the incidence of adverse events.DiscussionThis study will assess the efficacy and safety of bevacizumab in combination with single-agent chemotherapy, which could be used continuously after disease progression following standard platinum-based chemotherapy with bevacizumab.Trial registrationUMIN000017247 (registered April 22, 2015).

An open label, single arm, prospective phase II study to evaluate the efficacy and safety of bevacizumab with gemcitabine and carboplatin as first-line treatment for metastatic triple negative breast cancer patients.

1098Background: There is a higher burden (29.2%-46%) of TNBC patients in India. This single arm, phase II trial evaluated the efficacy and safety of bevacizumab in combination with gemcitabine and ...

Efficacy and safety of bevacizumab in combination with irinotecan and capecitabine in first-line treatment of metastatic colorectal carcer

Background/Aim. The efficacy and safety of bevacizumab (BEV) in combination with capecitabin and irinotecan in first-line therapy for patients with metastatic colorectal cancer (mCRC) were studied. In order to improve safety and efficacy of chemotherapy, as well as to reduce adverse reactions to a minimum, doses of active agents applied were changed in relation to previously employed schedules. Methods. Patients with histologically documented mCRC with no previously received chemotherapy or with received adjuvant or neoadjuvant chemotherapy, which ended 6 months before capecitabin treatment (1000 mg/m2 per os from the 2nd to 8th day of each cycle), irinotecan (175 mg/m2 iv every 2 weeks), plus bevacizumab (5 mg/kg iv every 2 weeks) were observed. Results. This prospective study included 35 patients of both sexes. The overall response rate (ORR) of 28.6%, partial response (PR) of 28.6%, progressive disease (PD) of 28.6% and stable disease (SD) of 42.8% were found. The progressionfree survival (PFS) of the analyzed patients was 11.3 (95% CL: 9.1?12.9) months while overall survival (OS) of the included patients was 25.2 (95% CL: 17.4?28.4) months and 117 adverse effects were recorded in 24 patients. Alopecia, nausea and vomiting, hemorrhage, hand-foot syndrome, diarrhea, abdominal pain, proteinuria, and hypertension (51.4%, 37.1%, 37.1%, 25.7%, 22.8%, 20.0%, 20.0% and 17.1%, respectively) were most frequently observed adverse effects. Conclusion. The results of this clinical trial support and recommend the use of bevacizumab plus capecitabin and irinotecan in the doses and schedule applied throughout this study as the first-line treatment of mCRC patients.

Efficacy and safety of addition of bevacizumab to FOLFIRI or irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer: A meta-analysis.

Recent studies have paid much attention on the safety of bevacizumab as adjuvant chemotherapy for metastatic colorectal cancer. The aim of this meta-analysis was to study the efficacy and safety of bevacizumab in combination with irinotecan, bolus followed by infusional 5-fluorouracil, and leucovorin (FOLFIRI) and, irinotecan, bolus fluorouracil, leucovorin (IFL) for patients with metastatic colorectal cancer (mCRC).An electronic search of related trials was conducted from PubMed, EMBASE, Cochrane Library databases. Risk ratio (RRs) and its 95% confidence intervals (95% CIs) were calculated by using either DerSimonian–Laird method or Mantel–Haenszel method according to the heterogeneity of included articles. The risk of mortality, therapeutic efficacy, and adverse effect were meta-analyzed.In total, 6 RCTs including 2165 participants (1109 in the treatment group, 1056 in the control group) were included in this meta-analysis. Compared with FOLFIRI-panitumumab/cetuximab, the bevacizumab addition significantly reduced the complete response (CR) rate (RR [95%CI] = 0.31[0.11, 0.89], P = 0.03) and the risk of grade 3/4 adverse event (RR [95%CI] = 0.89[0.80, 0.98], P = 0.01). Compared with FOLFIRI and IFL alone, the addition of bevacizumb significantly increased the partial response (PR) and objective response (OR) rates. Compared with IFL alone, the addition of bevacizumb significantly reduced the mortality risk of PFS (RR [95%CI] = 0.53[0.42, 0.66], P < 0.00001) and OS (RR[95%CI] = 0.70[0.60, 0.82], P < 0.00001), but increased the risk of adverse events (RR[95%CI] = 1.14[1.06, 1.21], P = 0.0002).Combination chemotherapy of bevacizumab plus FOLFIRI or IFL had a relative high efficacy and acceptable safety for treatment of mCRC.

Survival Benefit and Safety of Bevacizumab in Combination with Erlotinib as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: A Meta-Analysis.

Recently, the need for maintenance chemotherapy arose as a result of the significantly improved survival of patients with metastatic colorectal cancer (mCRC) without increasing adverse events. Currently used maintenance regimens are fluoropyrimidines, bevacizumab, and the combination of fluoropyrimidine with bevacizumab. A new combination with bevacizumab and erlotinib, a tyrosine kinase inhibitor of the epithelial growth factor receptor, has shown synergistic effects in preclinical tests and promising results in some clinical trials. Whether bevacizumab combined with erlotinib vs. bevacizumab alone as maintenance therapy will further improve the clinical outcomes in patients with mCRC is controversial. We conducted this meta-analysis to compare the survival benefit and safety of these two regimens in patients with mCRC. We searched PubMed, EMBASE, and the Central Registry of Controlled Trials of the Cochrane Library up to August 2016. We also searched the Proceedings of the American Society of Clinical Oncology (1986 to August 2016). Abstracts were manually searched to identify relevant trials. A total of three randomized controlled trials with 682 patients met the inclusion criteria. Our results demonstrated that bevacizumab combined with erlotinib significantly improved overall survival (hazard ratio 0.78; 95% confidence interval 0.66-0.93; p=0.006) and progression-free survival (hazard ratio 0.79; 95% confidence interval 0.68-0.92; p=0.002). Significantly more grade 3 rash, diarrhea, infection total, and fatigue were observed in the bevacizumab combined with erlotinib arm, which were controllable and reversible. Based on current evidence, the addition of erlotinib to bevacizumab as maintenance therapy significantly increases overall survival and progression-free survival with an increased but manageable toxicity in patients with mCRC. It should be considered as a treatment option for these patients under the premise of a reasonable selection of the target population.

A phase II study of bevacizumab in combination with irinotecan plus S-1 as first-line treatment in patients with KRAS mutant-type metastatic colorectal cancer.

676 Background: FOLFIRI+bevacizumab (BV) is considered as a first-line treatment in patients (pts) with metastatic colorectal cancer (mCRC). The FIRIS study showed the non-inferiority of irinotecan plus S-1 (IRIS) to FOLFIRI. Therefore, we conducted a phase II study to evaluate the efficacy and safety of BV in combination with IRIS as first-line chemotherapy for KRAS mutant-type (mt) mCRC (clinical trial information: UMIN000004630). Methods: Eligibility criteria included histologically confirmed mCRC, KRAS mt, no previous chemotherapy, ECOG performance status (PS) of 0/1, and adequate organ function. S-1 was administered at 80 mg/m2 on days 1–14 and irinotecan at 100 mg/m2 on days 1 and 15 every 28 days. BV was administered at 5 mg/kg on days 1 and 15 every 28 days. The primary endpoint was response rate (RR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. The sample size was calculated to reject a RR of 25% in favor of a target RR of 50% with a significance level of 0.05 and a statistical power of 80%. Results: Of 26 patients enrolled for the study between December 2010 and September 2015, 23 met the inclusion criteria. The patient characteristics were as follows: median age, 66 (range, 46–77) years; male/female, 15/8; PS 0/1, 9/14; number of metastatic tumors 1/ ≥ 2, 8/15; colon/rectum as the primary tumor site, 13/10; primary tumor +/−, 15/8; and unresectable/recurrent, 15/8. The RR was 60.9% (95% confidence interval (CI): 40.8%–77.8%) with complete response, 0; partial response, 14; stable disease, 8; progressive disease, 0; and not evaluable, 1. With a median follow-up period of 58.1 months, the median PFS and OS were 10.7 (95% CI: 4.7–16.8) and 28.5 (95% CI: 17.6–39.3) months, respectively. The most common grade 3 or 4 adverse events were neutropenia (35%), diarrhea (22%), leukopenia (17%), febrile neutropenia (13%), anemia (13%), and hypoalbuminemia (13%). Conclusions: BV in combination with IRIS as first-line chemotherapy showed promising anti-tumor effects and manageable toxicities for KRAS mt mCRC. Clinical trial information: UMIN000004630.

The Breast Avastin Trial: phase II study of bevacizumab maintenance therapy after induction chemotherapy with docetaxel and capecitabine for the first-line treatment of patients with locally recurrent or metastatic breast cancer

Therapeutic approach for patients with metastatic breast cancer (MBC) is still controversial. This study was conducted to assess the efficacy and safety of bevacizumab in combination with docetaxel plus capecitabine as first-line treatment for MBC. The feasibility of bevacizumab maintenance therapy in this setting was also evaluated. In this single-arm, multicenter phase II study, patients received bevacizumab 15 mg/kg and docetaxel 60 mg/m(2) on day 1, plus capecitabine 900 mg/m(2) twice daily on days 1-14 every 21 days. Treatment was administered for up to 6 cycles, then bevacizumab continued until progressive disease. The primary end point was progression-free survival (PFS); secondary end points were tumor response rate, overall survival, and toxicity. Seventy-nine eligible patients were treated with bevacizumab in combination with docetaxel plus capecitabine. The overall response rate was 61 %, with a complete response rate of 8 % and a median duration of response of 10 months. At a median follow-up of 28 months, the median PFS was 11 months. Fifty-two (65 %) patients received bevacizumab maintenance therapy for a median duration of 7 months (range 1 to 33+). Neutropenia was the most common grade 3-4 toxicity (28.1 % of patients), and two fatal adverse events occurred (septic shock and gastrointestinal perforation). Bevacizumab in combination with docetaxel and capecitabine demonstrates significant activity and quite acceptable toxicity profile as first-line treatment of MBC. Subsequent maintenance therapy with bevacizumab is feasible for a long period of stable disease. Results deserve confirmation.

O2-025 - Efficacy and Safety of Bevacizumab in Combination with Carboplatin and Paclitaxel for Patients with Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer

ABSTRACT Background Efficacy of bevacizumab in combination with platinum-based chemotherapy for EGFR mutation-positive non-small-cell lung cancer (NSCLC) is less well known. The purpose of this study was to determine the efficacy and safety of bevacizumab with carboplatin plus paclitaxel for patients with advanced EGFR mutation-positive NSCLC. Methods We retrospectively reviewed 22 consecutive patients with advanced EGFR mutation-positive NSCLC treated with bevacizumab with carboplatin plus paclitaxel at our institution from April 2010 to September 2011. Carboplatin AUC 6 and paclitaxel 200 mg/m2 for up to six cycles plus bevacizumab 15 mg/kg were administered intravenously every 3–4 weeks until disease progression or development of intolerance. Results Profile of patients included: median age was 63 years (range 36–71); male/female = 7/15; PS 0/1 = 4/18; EGFR mutation type exon 19 deletion/L858R in exon 21 = 11/11 and all patients had stage IV adenocarcinoma. Thirteen patients had received no prior chemotherapy and nine patients had been treated with EGFR tyrosine kinase inhibitors (EGFR TKIs). A partial response was achieved in 8 of 22 patients, and the overall response rate was 36%. The median progression-free survival (PFS) in all patients was 8.9 months. The response rate of patients who had received prior EGFR TKIs was 44% (4 of 9), as opposed to 31% (4 of 13) among untreated patients (P = 0.66). Median PFS was 8.9 months in prior EGFR TKIs-treated patients, compared with 6.1 months in untreated patients (P = 0.66). The median overall survival has not been reached. The most common adverse events were grade 3/4 neutropenia (45%) and grade 1 bleeding events (50%). There were no severe pulmonary hemorrhage and treatment-related deaths. Conclusions In patients with advanced EGFR mutation-positive NSCLC, prior EGFR TKIs therapy status is not significantly associated with efficacy of bevacizumab with carboplatin plus paclitaxel.

Irinotecan and Capecitabine (CAPIRI) Plus Bevacizumab in First-Line Treatment of Metastatic Colorectal Cancer

The purpose of this prospective study was to assess the efficacy and safety of bevacizumab in combination with reduced doses of irinotecan plus capecitabine (CAPIRI regimen), in patients with metastatic colorectal cancer (mCRC), as first-line chemotherapy. A cohort of 120 mCRC consecutive patients was included. The overall response rate was 63.3% (76 patients; 95% confidence interval [CI], 53.97%-71.77%). Median time to progression and overall survival were 15 months (range: 2-49 months; 95% CI: 13.00, 17.00 months) and 22.5 months (range: 4-54 months; 95% CI: 21.00, 27.00 months), respectively. The one year survival rate was 81.5%. CAPIRI-related grade 3/4 adverse events included alopecia (29.2%) and diarrhoea (16.7%), which were manageable. Bevacizumab-related grade 3 hypertension was reported in 2 patients. One patient died due to treatment related adverse event, which was no bevacizumab-related. In conclusion, combination of bevacizumab plus CAPIRI is a feasible treatment which provides a clinical benefit as first-line treatment in chemonaïve patients with mCRC.

Phase II Study of Bevacizumab in Combination with Trastuzumab and Capecitabine as First-Line Treatment for HER-2-positive Locally Recurrent or Metastatic Breast Cancer

We report the first results from a phase II, open-label study designed to evaluate the efficacy and safety of bevacizumab in combination with trastuzumab and capecitabine as first-line therapy for human epidermal growth factor receptor (HER)-2-positive locally recurrent (LR) or metastatic breast cancer (MBC). Patients were aged ≥18 years with confirmed breast adenocarcinoma, measurable LR/MBC and documented HER-2-positive disease. Patients received bevacizumab (15 mg/kg on day 1) plus trastuzumab (8 mg/kg on day 1 of cycle 1, 6 mg/kg on day 1 of each subsequent cycle) plus capecitabine (1,000 mg/m2 twice daily, days 1-14) every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. Eighty-eight patients were enrolled; 40 (46%) are still on study treatment. The median follow-up was 8.8 months (range, 0.9-17.1 months). The overall response rate, the primary endpoint, was 73% (95% confidence interval [CI], 62%-82%), comprising 7% complete and 66% partial responses. The median progression-free survival interval was 14.4 months (95% CI, 10.4 months to not reached [NR]), with 35 events. The median time to progression was 14.5 months (95% CI, 10.5 months to NR), with 33 events. Treatment was well tolerated; main side effects were grade 3 hand-foot syndrome (22%), grade ≥3 diarrhea (9%), and grade ≥3 hypertension (7%). Overall, 44% of patients experienced grade ≥3 treatment-related adverse events and 13 patients discontinued capecitabine because of toxicity, but continued with bevacizumab and trastuzumab. Heart failure was seen in two patients. The combination of bevacizumab, trastuzumab, and capecitabine was clinically active as first-line therapy for patients with HER-2-positive MBC, with an acceptable safety profile and no unexpected toxicities.

RIBBON-2: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy for Second-Line Treatment of Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

This phase III study compared the efficacy and safety of bevacizumab combined with standard chemotherapy regimens versus chemotherapy alone as second-line treatment of patients with human epidermal growth factor receptor 2 (HER2) -negative metastatic breast cancer. Patients were randomly assigned 2:1 to chemotherapy + bevacizumab or to chemotherapy + placebo. Before random assignment, investigators chose capecitabine, a taxane (paclitaxel, nab-paclitaxel, or docetaxel), gemcitabine, or vinorelbine. Dosing for bevacizumab or placebo was 15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks, depending on chemotherapy regimen. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, PFS by chemotherapy cohort, objective response rate (ORR), duration of objective response, 1-year survival rate, and safety. RIBBON-2 enrolled 684 patients (225, chemotherapy + placebo; 459, chemotherapy + bevacizumab). The combination of bevacizumab with chemotherapy demonstrated a statistically significant benefit. Median PFS increased from 5.1 to 7.2 months (stratified hazard ratio for PFS, 0.78; 95% CI, 0.64 to 0.93; P = .0072). The 10% improvement in ORR between the placebo- and bevacizumab-containing arms (39.5% v 29.6%; P = .0193), although not statistically significant, was consistent with previous trials. There was no statistically significant difference in overall survival. The most common grade ≥ 3 adverse events (AEs) related to bevacizumab treatment were hypertension (9.0%) and proteinuria (3.1%). There was an increased number of AEs leading to study discontinuation in the chemotherapy + bevacizumab arm compared with the chemotherapy + placebo arm (13.3% v 7.2%). The combination of bevacizumab with commonly used chemotherapies improved PFS in the second-line treatment of patients with HER2-negative metastatic breast cancer, with a safety profile comparable with that in prior phase III studies.

Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: Results from AVADO

BackgroundOncologic treatment in elderly patients is challenging, due to comorbidities, often impaired organ function, limited clinical trial evidence, inadequate guidelines and no consistent ‘elderly’ definition. We report exploratory sub-analyses of safety and efficacy in elderly patients, defined as ⩾65years old, in AVastin And DOcetaxel (AVADO) receiving first-line bevacizumab plus docetaxel for metastatic breast cancer (mBC). Patients and methodsPatients with HER2-negative, locally recurrent or mBC were randomised to 3-weekly docetaxel (100mg/m2) with placebo, bevacizumab 7.5mg/kg or bevacizumab 15mg/kg, for 9 cycles or until disease progression or unacceptable toxicity. Patients had no prior chemotherapy for mBC. ResultsProgression-free survival (PFS) was increased with bevacizumab in the elderly subpopulation (n=127), the effect being greater with higher dose (hazard ratio=0.63 [95% confidence interval (CI) 0.383–1.032] versus 0.76 [95% CI: 0.46–1.262], respectively). PFS was numerically similar in the elderly and overall populations, but the former failed to achieve statistical significance. Overall response rates for docetaxel plus placebo, bevacizumab 7.5mg/kg and 15mg/kg were 44.7%, 36.6% and 50.0%, respectively. Effects on survival were not statistically significant. Bevacizumab was well tolerated in elderly patients, the most common adverse effects were neutropenia and febrile neutropenia; there was no excess of grade⩾3 cardiovascular events. There was no clear correlation between baseline hypertension and its development during study treatment. ConclusionsIn this exploratory sub-analysis in AVADO, bevacizumab plus docetaxel showed efficacy in elderly patients similar to the overall study population. There were no unexpected safety signals in patients aged 65years or older.

Salvage with erlotinib plus bevacizumab: not in NSCLC

In The Lancet, Roy Herbst and colleagues report the phase 3, double-blind, randomised BeTa trial, 1 Herbst RS Ansari R Bustin F et al. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011; 377: 1846-1854 Summary Full Text Full Text PDF PubMed Scopus (338) Google Scholar in which they assessed the efficacy and safety of bevacizumab in combination with erlotinib, compared with erlotinib alone, for treatment of advanced non-small-cell lung cancer (NSCLC) after failure of first-line chemotherapy. The study was designed to detect a 33% improvement in median survival. However, overall survival did not differ between treatment groups, with a median overall survival of 9·3 months (IQR 4·1–21·6) for the 319 patients who received bevacizumab plus erlotinib and 9·2 months (3·8–20·2) for 317 patients who received erlotinib alone. Addition of bevacizumab to erlotinib therefore does not seem to improve survival in patients with recurrent or refractory NSCLC. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trialAddition of bevacizumab to erlotinib does not improve survival in patients with recurrent or refractory NSCLC. Full-Text PDF

Efficacy and safety of bevacizumab (BEV) plus chemotherapy in Chinese patients (pts) with metastatic colorectal cancer (mCRC): Results from the ARTIST study.

e14002 Background: BEV inhibits tumor angiogenesis by targeting vascular endothelial growth factor (VEGF). This randomized open-label multicenter study (ARTIST) evaluated the efficacy and safety of BEV in combination with modified IFL (mIFL) as first-line treatment for Chinese pts with mCRC. Methods: Pts >18 years with histologically confirmed, previously untreated, measurable mCRC and ECOG PS 0 or 1 were randomized 2:1 to BEV + mIFL or mIFL alone until disease progression, death, or unacceptable toxicities. mIFL (irinotecan 125 mg/m2, leucovorin 20 mg/m2 bolus, and 5-FU 500 mg/m2) was given weekly for 4 weeks every 6 weeks. BEV 5 mg/kg was given on Day 1 with chemotherapy, then every 2 weeks. Primary objectives were progression-free survival (PFS) and 6-month PFS rate; secondary objectives included overall survival (OS), overall response rate (ORR), response duration, and safety. Results: Between Jul 07 and Aug 08, 214 pts were enrolled at 12 centers in China (203 pts evaluable); final analysis was performed 10 months after the last pt was enrolled. Pt characteristics were balanced between arms. Addition of BEV to chemotherapy significantly improved PFS, 6-month PFS, OS, and ORR (table); risk of disease progression or death was reduced by 56% and risk of death by 38%. BEV plus mIFL was well tolerated; no grade 4/5 adverse events (AEs) of special interest, wound-healing complications, or episodes of congestive heart failure were reported (for grade 3 AEs see Table). Conclusions: The ARTIST study has shown that BEV plus mIFL is effective and well tolerated as first-line therapy for mCRC. The clinical benefit and safety profiles of BEV in Chinese pts are consistent with those observed in pivotal phase III multinational studies. Outcome (95% CI) BEV + mIFL mIFL p value Efficacy Evaluable patients 139 64 6-month PFS, % 62.6 (54.5–70.6) 25.0 (14.4–35.6) p<0.001 Median PFS, months 8.3 (7.4–8.9) 4.2 (3.7–4.9) p<0.001 HR=0.44 (0.31–0.63) Median OS, months 18.7 (15.8–19.6) 13.4 (9.7–17.2) p=0.014 HR=0.62 (0.41–0.95) ORR, % 35.3 (27.5–43.5) 17.2 (8.4–27.7) p=0.013 Safety Evaluable patients 141 70 Grade 3 hypertension, % 3.5 0 Grade 3 bleeding, % 0.7 1.4 Grade 3 GI perforation, % 0.7 0 No significant financial relationships to disclose.

RIBBON-2: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating the Efficacy and Safety of Bevacizumab In Combination with Chemotherapy for Second-Line Treatment of HER2-Negative Metastatic Breast Cancer.

Abstract Background: Three prior Phase III trials (E2100, AVADO, and RIBBON-1) established the clinical benefit of adding bevacizumab (BV) to various chemotherapies (chemos) as first-line treatment for metastatic breast cancer (MBC). A previous Phase III study (AVF2119g) in patients with predominantly heavily pre-treated MBC, in which BV was added to capecitabine (Cape), resulted in a significant increase in objective response rate (ORR), but did not meet the primary endpoint for progression-free survival (PFS). The current study, RIBBON-2, was designed to evaluate the efficacy and safety of the addition of BV to chemotherapies used as second-line treatment for MBC.Methods: Patients were randomized in a 2:1 ratio to chemo+BV or chemo+placebo (PL). Key eligibility criteria included one prior cytotoxic treatment for MBC, ECOG performance status of 0 to 1, and HER2-negative or unknown status. Prior to randomization, investigators chose one of the following chemo agents: taxane (T; paclitaxel 90 mg/m2/wk for 3 of the 4 weeks; paclitaxel 175 mg/m2, nab-paclitaxel 260 mg/m2, docetaxel 75–100 mg/m2, all given q3wk), gemcitabine (G; 1250 mg/m2 on Days 1 and 8 q3wk), Cape (2000 mg/m2 Days 1–14 q3wk), or vinorelbine (V; 30 mg/m2/wk). BV or PL was administered at 10 mg/kg q2wk or 15 mg/kg q3wk, depending on the chemo regimen. The primary endpoint of the study was investigator-assessed PFS pooled across the chemo cohorts. Key secondary endpoints included overall survival (OS), PFS within individual chemo cohorts, ORR, and safety.Results: 684 patients (T, 304; G, 160; Cape, 144; and V, 76) at 211 sites in 19 countries were randomized between February 2006 and June 2008. Overall, the two study arms were balanced for patient characteristics at baseline. The study met its primary endpoint of PFS pooled across chemo cohorts and also demonstrated a 10% increase in ORR when BV was added to chemo. At the interim analysis for OS, the median durations were 18 mo for chemo+BV and 16.4 mo for chemo+PL (see table).Across all chemo cohorts the incidence of BV-related AEs was consistent with data from previous studies. Hypertension was the only BV-related AE consistently increased in the chemo+BV arm across all chemo cohorts.Conclusions: The addition of BV to chemotherapies used for second-line treatment of MBC led to a significant improvement in PFS. The AE profile of BV in the overall study population and across the chemotherapy cohorts was consistent with that previously observed. Additional analyses, including PFS for the individual chemo cohorts, will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 42.

Efficacy and safety of bevacizumab (BEV)-based combination regimens in patients with metastatic colorectal cancer (mCRC): Randomized phase II study of BEV + FOLFIRI versus BEV + XELIRI (FNCLCC ACCORD 13/0503 study)

4086 Background: The combination of BEV and chemotherapy is highly effective in patients with mCRC and improves response rate, progression-free survival and overall survival compared with chemotherapy alone. This randomized non-comparative phase II trial evaluated the efficacy and safety of BEV in combination with either XELIRI or FOLFIRI as first-line therapy for mCRC. Methods: Patients were eligible for inclusion in this study if they had histologically proven measurable mCRC, were aged 18–75 years, and had an ECOG performance status (PS) of 0–2. Patients were treated with 8 cycles of XELIRI (irinotecan 200 mg/m2 on Day 1 and capecitabine 1000 mg/m2 bid on Days 1–14) + BEV 7.5 mg/kg on Day 1, every 3 weeks or 12 cycles of FOLFIRI (irinotecan 200 mg/m2 on Day 1 + 5-fluorouracil (5-FU) 400 mg/m2 + folinic acid 400 mg/m2 on day 1 followed by 5-FU 2400 mg/m2 via 46-h infusion) + BEV 5 mg/kg on day 1, every 2 weeks. BEV was continued to disease progression. Patients aged ≥65 years received a lower daily dose of capecitabine (800 mg/m2 bid). The primary endpoint was crude progression-free survival (PFS) at 6 months. Results: In total, 145 patients were entered in the study between March 2006 and January 2008; 72 patients received BEV + XELIRI and 73 patients received BEV + FOLFIRI (male 64%/48%; median age 61/61 years; 35/36% aged &gt;65 years). Preliminary results from the first 6 months of follow-up are reported here. A total of 491/783 cycles was administered, 63%/67% receiving at least the initially planned number of cycles (8 cycles for BEV + XELIRI and 12 for BEV + FOLFIRI). Main results are given in the table . Conclusions: This randomized non-comparative study has shown that BEV + XELIRI and BEV + FOLFIRI are similarly effective treatments for patients with mCRC, with manageable toxicity profiles. Results with updated follow-up will be presented at the Meeting. [Table: see text] [Table: see text]