Received Maintenance Bevacizumab Research Articles

Real-world efficacy and safety of bevacizumab single-maintenance therapy following platinum-paclitaxel chemotherapy plus bevacizumab in patients with advanced cervical cancer.

Bevacizumab maintenance therapy following platinum-based combination chemotherapy for metastatic, recurrent, or persistent cervical cancer is not recommended as standard therapy. This pilot study aimed to evaluate the efficacy and safety of bevacizumab maintenance therapy and the contribution of the platinum-free interval to the efficacy of subsequent chemotherapy for advanced cervical cancer. We retrospectively identified 115 patients with metastatic, recurrent, or persistent cervical cancer treated with platinum-paclitaxel chemotherapy plus bevacizumab at 7 institutions between 2015 and 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients who received bevacizumab maintenance therapy and those who did not. We also analyzed the adverse events associated with bevacizumab and survival time from the start of subsequent chemotherapy in both groups. Following platinum-paclitaxel plus bevacizumab chemotherapy, 34 patients received bevacizumab maintenance therapy and 81 patients did not. Of the 115 patients, 56 received chemotherapy for subsequent relapse. Although bevacizumab maintenance therapy prolonged PFS (median of 16.0 months vs. 9.0 months, p=0.041), significant differences were not observed in OS (p=0.374). Furthermore, bevacizumab maintenance therapy did not prolong OS and PFS after the start of subsequent chemotherapy (p=0.663 and p=0.136, respectively). Bevacizumab maintenance therapy significantly increased hypertension (p=0.035) and proteinuria (p=0.005) but did not cause complications leading to death. Bevacizumab single-maintenance therapy for advanced cervical cancer can be considered in selected cases, such as those with acceptable bevacizumab-related side effects. The outcomes of our study will likely contribute to decision-making regarding practical treatment strategies.

Paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy for metastatic, recurrent, and persistent uterine cervical cancer: An open-label multicenter phase II trial (JGOG1079)

ObjectiveThis multicenter, open-label, phase II study aimed to evaluate the efficacy and safety of paclitaxel–carboplatin, bevacizumab, and bevacizumab-based maintenance therapy for metastatic, recurrent, and persistent uterine cervical cancer. MethodsPatients with measurable diseases that were not adapted to regional therapies, such as surgery or radiotherapy, and were systematic chemotherapy-naïve were eligible. The participants received paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) every three weeks until disease progression or unacceptable adverse events occurred. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), overall survival (OS), safety, and time to treatment failure. ResultsSixty-nine patients were analyzed using our protocol. The median paclitaxel– carboplatin therapy duration was six cycles; 40% of patients received bevacizumab maintenance therapy. The median PFS was 11.3 months. The median OS was not reached; the median time to treatment failure was 5.9 months. The ORR was 79.7% [95% confidence interval (CI) 63.8–88.4]; 16 patients (23.2%) showed complete response (CR) and 39 patients (56.5%) showed partial response (PR). The median PFS was 14.3 months (95% CI 7.3–17 months) for the 25 patients who received maintenance therapy and 7.4 months (95% CI 6.1–11 months) for nonrecipients (p = 0.0449). Gastrointestinal perforation/fistulas occurred in four patients (5.6%), all of whom had a history of radiation therapy. ConclusionsPaclitaxel–carboplatin and bevacizumab therapy is an acceptable and tolerable treatment for advanced or recurrent cervical cancer.

Primary results from CECILIA, a global single-arm phase II study evaluating bevacizumab, carboplatin and paclitaxel for advanced cervical cancer

ObjectiveAdding bevacizumab to cisplatin–paclitaxel for advanced cervical cancer significantly improves overall and progression-free survival. We evaluated bevacizumab with a widely used carboplatin–paclitaxel backbone. MethodsPatients with metastatic/recurrent/persistent cervical cancer not amenable to curative surgery and/or radiotherapy received 3-weekly bevacizumab 15 mg/kg, paclitaxel 175 mg/m2, and carboplatin AUC 5 until progression or unacceptable toxicity. Maintenance bevacizumab was allowed. Patients with ongoing bladder/rectal involvement, prior cobalt radiotherapy, a history of fistula/gastrointestinal perforation, or recent bowel resection/chemoradiation were excluded. The primary objective was to determine incidences of gastrointestinal perforation/fistula, gastrointestinal-vaginal fistula, and genitourinary fistula. ResultsAmong 150 treated patients, disease at study entry was persistent in 21%, recurrent in 56%, and newly diagnosed metastatic in 23%. After 27.8 months' median follow-up, median bevacizumab duration was 6.7 months; 57% received maintenance bevacizumab. Seventeen patients (11.3%; 95% CI: 6.7–17.5%) experienced ≥1 perforation/fistula event: gastrointestinal perforation/fistula in 4.7% (1.9–9.4%), gastrointestinal-vaginal fistula in 4.0% (1.5–8.5%), and genitourinary fistula in 4.7% (1.9–9.4%). Of these, 16 were previously irradiated, several with ongoing radiation effects. The most common grade 3/4 adverse events were neutropenia (25%), anemia (19%), and hypertension (14%). Five patients (3%) had fatal adverse events. Objective response rate was 61% (95% CI: 52–69%), median progression-free survival was 10.9 (10.1–13.7) months, and median overall survival was 25.0 (20.9–30.4) months. ConclusionsBevacizumab can be combined with carboplatin–paclitaxel in the CECILIA study population. The fistula/gastrointestinal perforation incidence is in line with GOG-0240; efficacy results are encouraging.Trial registration number.NCT02467907 (ClinicalTrials.gov).

The efficacy and safety of bevacizumab in addition to platinum-based chemotherapy for the first-line treatment of patients with advanced nonsquamous non-small-cell lung cancer: Final results of AVALANCHE, an observational cohort study.

The previous results of former clinical studies confirmed that first-line bevacizumab (BEV) in combination with chemotherapy improves clinical outcomes in patients with advanced non-squamous non-small cell lung cancer. The AVALANCHE study (ClinicalTrials.gov Identifier NCT03170284) was undertaken to assess the clinical outcomes of first-line BEV combined with standard platinum-based regimens in the Hungarian clinical practice. This observational study was conducted in 28 Hungarian sites, with patients enrolled between July 2008 and April 2011. Patients with untreated locally advanced, metastatic or recurrent lung adenocarcinoma received BEV (7.5 mg/kg, q3w) with any platinum-doublet for up to 6 cycles, and then non-progressors proceeded to receive BEV until disease progression or unacceptable toxicity. The primary endpoint was time-to-progression, and secondary endpoints included overall survival (OS), tumour control rate and safety. Patients were also analysed as two cohorts (non-progressors vs. progressors) based on whether or not they received BEV maintenance therapy following completion of first-line chemotherapy plus BEV. The study enrolled 283 patients (median age: 58.2 (18–78) years; males: 50.5%; stage: III/B: 18.4%, IV: 79.9%; adenocarcinoma/other: 95.8/4.2%; ECOG PS 0/1/2/≥3: 30.8/59.7/2.6/1.4%). Centrally located tumours were reported in 21.6%. Cisplatin/carboplatin-based regimens: 53.8/46.2%. A total of 43% of patients received BEV maintenance therapy. The median number of BEV cycles was 6. Median progression-free survival (PFS) was 7.2 months and OS was 15.2 months for the entire cohort. Longer PFS and OS were observed in patients who received BEV maintenance therapy [median OS, 26.2 vs. 10.2 months (P<0.001); median PFS, 9.2 vs. 5.8 months (P<0.001)]. Contrary to the results of previous OCS no significant difference was recorded in the different age groups or gender. Best tumour response: Complete remission/partial remission/stable disease/progressive disease/not reported were: 1.5/29.9/26.9/9.1/32.6% of all patients. In conclusion, clinical outcomes obtained in this real-life population were consistent with pivotal studies. BEV maintenance treatment was associated with a significantly longer PFS and OS.

Evaluation of Natriuretic Peptide in Non-small Cell Lung Cancer Patients Treated with Bevacizumab Together with Carboplatin-Paclitaxel: A Prospective Study.

To identify predictive markers for efficacy of combination bevacizumab and carboplatin-paclitaxel treatment in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Twenty patients received carboplatin (area under the concentration-time curve (AUC) 6 mg/ml×min) and paclitaxel (200 mg/m2) with bevacizumab (15 mg/kg) on day 1 of a 21-day cycle. After four cycles of induction therapy, patients received bevacizumab maintenance therapy until disease progression or unacceptable toxicity occurred. Plasma and serum samples (baseline, day 8 and before cycle 2) were analyzed for natriuretic peptide content. Plasma brain natriuretic peptide (BNP) levels were significantly decreased at day 8 (20.1±4.0 pg/ml vs. 9.1±1.8 pg/ml, p=0.0002). Patients whose plasma BNP level was reduced to <50% of the baseline at day 8 had a longer progression-free survival (PFS) than those with a less decrease (9.73 versus 2.63 months, p=0.00013). In multivariate Cox analysis, decrease of plasma BNP concentration was associated with a longer PFS (p=0.0022). Decrease of plasma BNP concentration correlated with PFS after a treatment of combination bevacizumab plus carboplatin-paclitaxel.

ED13.05 Systemic Therapy of Inoperable Malignant Pleural Mesothelioma

ED13.05 Systemic Therapy of Inoperable Malignant Pleural Mesothelioma

P3.02c-015 Phase II Trial of S-1/Cisplatin Combined with Bevacizumab for Advanced Non-Squamous Non-Small Cell Lung Cancer: TCOG LC-1202: Topic: Targeted Therapy

S-1 plus cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC) (Ann. Oncol. 2015; 26:1401-8). The addition of bevacizumab significantly improved overall survival (OS) in patients with advanced non-squamous (non-SQ) NSCLC who received carboplatin plus paclitaxel but failed to show an OS advantage in patients who received cisplatin plus gemcitabine. Few studies of bevacizumab have evaluated quality of life (QOL) in patients with non-SQ NSCLC. Chemotherapy-naïve patients with stage IIIB, IV, or recurrent non-SQ NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–1, age 20–74 years, and measurable lesions were treated with a 3-week cycle of S-1 40 mg/m2 twice a day on days 1–14, cisplatin 60 mg/m2 on day 8, and bevacizumab 15 mg/kg on day 8, for 4–6 cycles. Patients without progressive disease received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 40 mg/m2 twice a day every other day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), OS, toxicity profile, and QOL. From June 2013 to January 2015, 39 evaluable patients were enrolled from 8 institutions: 10 women and 29 men; median age 65 (range, 38–74) years; epidermal growth factor receptor positive/anaplastic lymphoma kinase positive: two patients/two patients; performance status 0/1: 22/17; stage IIIB/IV/recurrence: 1/35/3; adeno/large cell/other: 35/1/3. Thirty one patients (80%) completed 4 cycles of induction chemotherapy, and 23 patients (59%) were started on maintenance chemotherapy. Median PFS, OS, and ORR were 7.3 months (95% confidence interval (CI): 5.9–8.7), 21.4 months (95% CI: 14.7–not reached), and 64%, respectively. The worst hematologic and non-hematologic adverse events were as follows (%): grade 3/4 leukopenia: 13/0; neutropenia: 18/5; thrombocytopenia: 0/0; anemia: 0/0; neutropenic fever: 3/0; and hypertension: 28/0; diarrhea: 3/0. QOL data will be presented at the meeting. S-1 plus cisplatin in combination with bevacizumab met the primary endpoint in patients with advanced non-SQ NSCLC in the present trial. Additionally, the response rate is anticipated to be high, and the regimen was well tolerated. Clinical trial information: UMIN000009476.

P3.02c-020 More Than 3 Years Long-Term Maintenance Treatment of Bevacizumab for Advanced-Stage NSCLC: A Report of Three Cases: Topic: Targeted Therapy

Bevacizumab has proven efficacy in extending OS and PFS as first-line treatment for advanced nonsquamous NSCLC. There were three advanced NSCLC patients received maintenance with bevacizumab for more than 3 years in our hospital, and here we share the data of these patients. All three patients with advanced-stage lung adenocarcinoma received bevacizumab (15mg/kg) plus paclitaxel and carboplatin for 6 cycles as first-line treatment and bevacizumab maintenance. In the maintenance, proteinuria occurred in all three patients after 6 months of treatment or longer and caused cessation of bevacizumab in two patients. It’s noteworthy that two patients presented spleen changes after long-term maintenance. In patient 01, proteinuria occurred after 8 cycles of bevacizumab, caused cessation of 7 doses, and lasted till one year after discontinuation of bevacizumab. In patient 02, splenomegaly was found after 44 cycles of bevacizumab, caused treatment discontinuation, and reversed after 6 months of discontinuation. In patient 03, proteinuria occurred after 29 cycles of bevacizumab and caused cessation of 5 doses of bevacizumab. Besides, increased serum creatinine and blood urea nitrogen were found after 18 months of protienuria, and CT scan indicated wedge-shaped defects in spleen after 55 cycles. After disease progression or discontinuation of bevacizumab, two patients were confirmed harboring EGFR mutations and received EGFR TKI treatment. The other patient, EGFR mutation and ALK-arrangement negative, received chemotherapy after disease progression. These patients received bevacizumab maintenance for more than 3 years were all enrolled in clinical trials, and the long-term maintenance brought them adverse effects as well as clinical benefit. In the real world, the cycles of maintenance and the best total dosage of bevacizumab for NSCLC remain uncertain. Is it true that the longer the treatment lasts, the more benefit the patients get with the maintenance treatment of bevacizumab?

Bevacizumab en association à une première ligne de chimiothérapie chez des patients atteints d’un cancer bronchique non à petites cellules, non épidermoïde, à un stade avancé ou en rechute : résultats de l’étude non interventionnelle EOLE

The EOLE cohort aimed to describe, in routine clinical practice, the characteristics and management of patients receiving bevacizumab in combination with first-line metastatic chemotherapy for advanced metastatic or recurrent non squamous non-small cell lung cancer (nsNSCLC), as well as its efficacy and safety. A total of 423patients were enrolled in this prospective, national, multicenter study. Data were collected every 3months over an 18-month period. Amongst the 407patients analyzed (mean age 60±10years, male 68%, ECOG-PS≤1 88%, smokers or former smokers 87%, cardiovascular comorbidities 40%), all except for 2patients received bevacizumab (7.5 or 15mg/kg/3weeks in 99% of patients) in combination with doublet chemotherapy. A total of 160 (60%) patients who completed induction received bevacizumab maintenance therapy. Median progression-free survival was 6.9months (95% CI=[6.0-7.5]). Median overall survival (12.8 months [10.4-14.7]) was longer in patients with ECOG-PS≤1 (14.4 months [12.3-15.9] versus 4.9 months [3.4-8.3] if ECOG-PS=2). A total of 131 (32%) patients experienced at least one serious adverse event (SAE), and 51 (12%) at least one bevacizumab-related SAE. EOLE confirms the efficacy and safety of bevacizumab in aNSCLC patients, in current medical practice.

Quantitative measurement of adiposity using CT images to predict the benefit of bevacizumab-based chemotherapy in epithelial ovarian cancer patients.

The present study aims to quantitatively measure adiposity-related image features and to test the feasibility of applying multivariate statistical data analysis-based prediction models to generate a novel clinical marker and predict the benefit of epithelial ovarian cancer (EOC) patients with and without maintenance bevacizumab-based chemotherapy. A dataset involving computed tomography (CT) images acquired from 59 patients diagnosed with advanced EOC was retrospectively collected. Among them, 32 patients received maintenance bevacizumab following primary chemotherapy, while 27 did not. A computer-aided detection scheme was developed to automatically segment visceral and subcutaneous fat areas depicted on CT images of abdominal sections, and 7 adiposity-related image features were computed. Upon combining these features with the measured body mass index, multivariate data analyses were performed using three statistical models (multiple linear, logistic and Cox proportional hazards regressions) to analyze the association between the model-generated prediction results and the treatment outcome, including progression-free survival (PFS) and overall survival (OS) of the patients. The results demonstrated that applying all three prediction models yielded a significant association between the adiposity-related image features and patients' PFS or OS in the group of the patients who received maintenance bevacizumab (P<0.010), while there was no significant difference when these prediction models were applied to predict both PFS and OS in the group of patients that did not receive maintenance bevacizumab. Therefore, the present study demonstrated that the use of a quantitative adiposity-related image feature-based statistical model may generate a novel clinical marker to predict who will benefit among EOC patients receiving maintenance bevacizumab-based chemotherapy.

Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer: single center experience.

BackgroundMetastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients’ register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer.Patients and methodsThe registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories.ResultsBetween January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (≥ 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7–16.2) and 11.3 (95% CI, 10.2–12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4–28.9) and 27.4 (95% CI, 22.7–31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21/22 %, hypertension 25/19 %, haemorrhage 2/4 % and thromboembolic events 10/6 %, for elderly and < 70 years group, respectively.ConclusionsIn routine clinical practice, the combination of bevacizumab and chemotherapy is effective and well-tolerated regimen in elderly patients with metastatic colorectal cancer.

Phase II study of oral S-1 plus cisplatin with bevacizumab for advanced non-squamous non-small cell lung cancer

BackgroundWe conducted a phase II study to evaluate the efficacy and safety of S-1 plus cisplatin with bevacizumab followed by maintenance bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Patients and methodsChemotherapy-naïve patients received S-1 plus cisplatin with bevacizumab. S-1 (80mg/m2) was administered orally twice daily for 14 days, cisplatin (60mg/m2) on day 1, and bevacizumab (15mg/kg) on day 1 and every 3 weeks for 4–6 cycles. Patients with an objective response or stable disease received maintenance bevacizumab every 3 weeks until disease progression. ResultsThirty patients were enrolled in this study. The median number of chemotherapy was four (range, 1–6 cycles), and the median number of bevacizumab alone was three (range, 1–31 cycles). The grade 3/4 toxicities were neutropaenia (23%), thrombocytopaenia (10%), febrile neutropaenia (3%), hypertension (17%), pneumonia (7%), and bowel perforation (3%). The objective response rate was 71% (95% CI, 55–88%) for a disease control rate of 100%. The median progression-free and overall survival times were 7.0 months and 20.0 months, respectively. ConclusionsS-1 plus cisplatin with bevacizumab is an active and well-tolerated regimen in patients with chemotherapy-naïve non-squamous NSCLC.

Survival analysis of induction cisplatin (CDDP)-docetaxel (DOC)-bevacizumab (BEV) chemotherapy followed by maintenance BEV-pemetrexed (PEM) therapy in advanced nonsquamous non-small cell lung cancer (NonSq NSCLC): A phase II trial from Okayama Lung Cancer Study Group 0903.

e19040 Background: BEV maintenance therapy and PEM maintenance therapy in platinum-based chemotherapy yield a significant survival advantage in CALGB and PARAMUNT trials, respectively, but each agent gave only modest impact on survival. We conducted a phase II trial of CDDP-DOC-BEV therapy followed by maintenance BEV-PEM therapy inchemo-naïve advanced NonSq NSCLC. Methods: Forty-one patients (pts) participated in the induction phase, specified as four cycles of induction CDDP (80 mg/m2), DOC (60 mg/m2) and BEV (15 mg/kg) on day 1 of a 21-day cycle. Pts who had not progressed during CDDP-DOC-BEV received maintenance BEV (15 mg/kg) and PEM (500 mg/m2) on day 1 of a 21-day cycle until disease progression. The primary endpoint was PFS, and the secondary endpoints included OS, toxicity, and response. Survival time was calculated from the date of registration. Results: Pt characteristics were as follows: median age: 62 yrs; 76% male; 32% PS 0; 73% stage IV; 93% Ad; 5% EGFR-mutant and 2% ALK-mutant. At the time of this analysis, 34 pts (83%) discontinued the treatment, mainly due to progressive disease (53%). The principal toxicity was myelosuppression (gr. 4 hematological: 21 pts [51%]), and grs. 3/4 febrile neutropenia was observed in 10 (24%) despite no treatment-related deaths. The objective response rate and disease control rate (DCR, % pts with CR/PR/SD) was 82.9% and 97.6%, respectively. Median follow-up time was 15.6 months, and 1-yr PFS rate was 34.2% with 95% confidence interval (CI) of 20.3-48.5%, which met the primary endpoint. Also, 1-yr OS rate was 75.6% (95%CI: 59.4-86.1%). Exploratory analysis for pts with both EGFR- and ALK-wild-typed NonSq NSCLC (n = 16) demonstrated 1-yr PFS and OS rates of 50.0% (24.5-71.1%) and 87.5% (58.6-96.7%), respectively. Also, pts with maintenance therapy (n = 34) had 1-yr PFS and OS rates of 41.2% (24.8-56.9%) and 82.4% (64.9-91.7%), respectively. Conclusions: CDDP-DOC-BEV followed by BEV-PEM maintenance seems highly effective despite moderately toxic profiles in chemo-naïve pts with advanced NonSq NSCLC. Clinical trial information: UMIN000004127.

Efficacy and safety of paclitaxel and carboplatin with bevacizumab for the first-line treatment of patients with nonsquamous non-small cell lung cancer (NSCLC): Analyses based on age in the phase III PointBreak and E4599 trials.

8073 Background: A post hoc analysis of NSCLC (pts) ≥70 y in the pivotal E4599 trial found increased adverse events (AEs) and numerically decreased survival benefit associated with bevacizumab (BEV) vs pts &lt;70 y. We evaluated the efficacy and safety of BEV by age in pts in a pooled dataset from the E4599 and PointBreak (PB) trials. Methods: Pts randomized to the PC (paclitaxel and carboplatin ) + BEV arms of E4599 and PB received P 200 mg/m2, C AUC 6, and BEV 15 mg/kg q3w for 6 (E4599) or 4 (PB) cycles; 1 pt in PB received 6 cycles. Eligible pts received maintenance BEV q3w until disease progression or unacceptable toxicity. Overall survival (OS), progression-free survival (PFS), and safety were assessed in pts grouped according to age (&lt;65 y, 65–75 y, 70–75 y, &lt;75 y, and ≥75 y). Pt-level data from the PC + BEV arms of E4599 and PB were pooled and compared with data from pts in the PC-alone arm of E4599. Results: PB and E4599 randomized 467 pts and 434 pts to PC + BEV, respectively. Baseline characteristics were balanced between age groups. OS and PFS hazard ratios (HRs) and increases in grade ≥3 AEs for the pooled pt cohort relative to E4599 PC-alone arm are shown (Table). Outcomes were similar in pts &lt;70 y and ≥70 y, and data from the pooled population were similar to those seen in each individual trial (data not shown). Conclusions: In a pooled exploratory analysis of pt data from E4599 and PB, the statistically significant benefit associated with the addition of BEV to PC appeared consistent across all age groups &lt;75y. Pts ≥75 y receiving BEV had a higher incidence of grade ≥3 AEs relative to PC alone with no statistically significant survival benefit, although an increase in grade ≥3 AEs was observed in all age groups. Clinical trial information: NCT00762034 and NCT00021060. [Table: see text]

Carboplatin plus paclitaxel in combination with bevacizumab for the treatment of adenocarcinoma with interstitial lung diseases

Interstitial lung diseases (ILDs) are frequently associated with lung cancer. The safety of carboplatin plus paclitaxel in combination with bevacizumab (CP-B) in patients with ILD and lung cancer (ILD-LC) remains to be clarified. In the present study, the safety and efficacy of CP-B treatment in ILD-LC patients were retrospectively investigated. Four patients, who completed CP-B therapy, were included in this study. The dose of carboplatin was the area under the curve 5, paclitaxel was 200 mg/m2 and bevacizumab was 15 mg/kg at treatment initiation. The patients were males, had histologically confirmed adenocarcinoma, were smokers and demonstrated non-usual interstitial pneumonia (non-UIP) patterns on computed tomography (CT). Patients received 1-6 cycles of CP-B therapy. Three of the four patients received maintenance bevacizumab therapy for 3-10 cycles. Only one patient demonstrated a partial response. Neutropenia was the most frequent adverse event. One patient experienced gut perforation during the first course of CP-B. No pulmonary toxicity was observed. Thus, treatment of ILD-LC patients with CP-B was not associated with pulmonary toxicity, however, this study population appeared to be at a low risk.

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.

Bevacizumab Maintenance in Patients with Advanced Non–Small-Cell Lung Cancer, Clinical Patterns, and Outcomes in the Eastern Cooperative Oncology Group 4599 Study: Results of An Exploratory Analysis

The Eastern Cooperative Oncology Group (ECOG) 4599 study showed a significant survival benefit with the use of bevacizumab (BV) in combination with carboplatin and paclitaxel (CP) in comparison with CP chemotherapy alone in patients with previously untreated advanced, metastatic or recurrent non-small-cell lung cancer (NSCLC). Such results were achieved using BV as maintenance therapy until progressive disease. Because current data on single-agent BV maintenance in non-small-cell lung cancer are limited, we present a retrospective analysis of safety and efficacy outcomes for patients who received maintenance BV after induction treatment and the maintenance-eligible population of the control arm in ECOG 4599. Landmark analyses were conducted in patients in both the CP and CP+BV groups who were alive and progression free through the completion of six cycles + 21 days. The BV maintenance population consisted of patients in the CP+BV arm, who were alive without progressive disease before the start of maintenance (maintenance-nonprogressor population). CP nonprogressors were those patients in the CP-alone arm without progressive disease after six cycles of CP + 21 days. Two hundred and seventeen patients (51%) were alive, progression free, and eligible for maintenance therapy six cycles + 21 days after induction CP+ BV compared with 134 patients (30%) in the CP-alone arm. Postinduction progression-free survival was significantly longer in the BV maintenance group relative to CP nonprogressors (4.4 versus 2.8 months; hazards ratio [HR] 0.64; p < 0.001). One-year overall survival rates were 75% for the BV maintenance group versus 69% in the CP nonprogressor group. Two-year overall survival rates were 34% for the BV maintenance group versus 25% in the CP nonprogressor group. Median postinduction overall survival (OS) was also significantly longer for the BV-maintenance group compared with CP nonprogressors (12.8 versus 11.4 months; HR 0.75; p = 0.030). Within the subgroup having complete response or partial response after induction, the progression-free survival and OS hazard ratio estimates were 0.59 (95% [confidence interval] CI: 0.41-0.84) and 0.78 (95% CI: 0.53-1.14), respectively. In the maintenance setting, BV was associated with a less-than 1% rate of grade 3 or 4 hematological toxicities, no grade 3 or 4 nausea, vomiting or diarrhea, and no grade 5 toxicities. In this retrospective analysis of patients in the ECOG 4599 study, who were alive, progression free, and on-study 21 days after six cycles of induction therapy, significant reductions in HRs for progression (0.64, p < 0.001) and survival (0.75, p = 0.03) were associated with BV treatment during induction and maintenance compared with CP induction therapy alone and suggestive of possible benefit because of bevacizumab maintenance.

Evaluating the Impact of Bevacizumab Maintenance Therapy on Overall Survival in Advanced Non–Small-Cell Lung Cancer

BackgroundIn patients with advanced-stage non–small-cell lung cancer (NSCLC) with nonsquamous histology, bevacizumab maintenance therapy after initial combination with platinum-based chemotherapy has been approved in the United States and Europe. In this study, a comparative effectiveness analysis of bevacizumab maintenance therapy after initial chemotherapy with bevacizumab is described. MethodsA retrospective analysis of patients treated in 17 community oncology practices across the United States was conducted. Inclusion criteria consisted of patients with stage IIIb or IV disease who received bevacizumab maintenance after an initial first-line induction regimen. Overall survival (OS) was evaluated by using the method of Kaplan-Meier and Cox proportional hazard modeling. To control for selection bias that is inherent in observational studies, an 18-week landmark and propensity score analysis was conducted. The hazard ratio (HR) for OS was then evaluated in a sensitivity analysis. ResultsA total of 272 patients with advanced-stage NSCLC met the inclusion criteria. Only 74 (27.2%) patients received bevacizumab maintenance therapy. Patients in the bevacizumab maintenance group tended to be younger and fitter, with a more favorable disease profile, which resulted in an improvement in the crude unadjusted OS (23.1 vs. 10.3 months; hazard ratio (HR) 0.44 [95% CI, 0.32-0.59]). Landmark and propensity score analyses supported the finding of a reduced risk of death with bevacizumab maintenance therapy (HR 0.52 [95% CI, 0.37-0.73] for landmark analyses and HR 0.70 [95% CI, 0.39-1.28] for propensity score analyses). ConclusionsBevacizumab maintenance therapy contributed to an OS benefit in this retrospective sample of patients with NSCLC, even after multiple statistical adjustments for selection bias.

First-line bevacizumab, cisplatin and vinorelbine plus maintenance bevacizumab in advanced non-squamous non-small cell lung cancer chemo-naïve patients

Objective: The aim of this study was to evaluate efficacy and safety of first-line treatment with bevacizumab, cisplatin and vinorelbine and bevacizumab maintenance in non-squamous, non-small cell lung cancer (NSCLC).Research design and methods: Forty-nine patients with stage IIIB plus pleural effusion or stage IV NSCLC were included in a Phase II clinical trial. Treatment consisted of 3-week cycles of bevacizumab (15 mg/kg on day 1), cisplatin (80 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1 and 8). After 6 cycles, non-progressing patients received bevacizumab maintenance therapy. The primary end point was progression-free survival (PFS), calculated using the Kaplan–Meier method.Results: Thirteen (29%) of 45 evaluable patients presented a partial response. PFS and overall survival were 6.0 months (95% confidence interval (CI) 4.5 – 7.5) and 14.7 months (95% CI 8.4 – 21), respectively. Fourteen patients (28%) experienced grade 3 – 4 neutropenia and 7 (14%) experienced febrile neutropenia during the combination treatment. During the maintenance phase, the most frequent grade 3 – 4 adverse event was hypertension. Neither grade 3 – 4 thrombocytopenia nor toxic death was observed.Conclusions: The studied regimen achieved a similar efficacy to other regimens containing platinum doublets. The data provide further evidence that bevacizumab may be used in combination with multiple standard platinum-based doublets in this setting.

IFCT-GFPC-0701 MAPS trial, a multicenter randomized phase III trial of pemetrexed-cisplatin with or without bevacizumab in patients with malignant pleural mesothelioma (MPM).

TPS7112 Background: MPM median OS does not exceed 13 months with pem/CDDP doublet. U.S. Intergroup phase II trial of gemcitabine/CDDP, with or without bevacizumab, gave an appealing 15.6 months median OS in the bevacizumab arm. French Intergroup aimed to test pem/CDDP with bevacizumab (PCB), in a randomized phase III trial. Methods: Eligible patients had unresectable histologically proved MPM, no prior chemo, PS 0-2, no thrombosis, nor bleeding. Primary endpoint: The primary outcome will be survival. The secondary endpoint will be Progression-Free Survival. Patients received pem 500 mg/m2, CDDP 75 mg/m2 (PC),at D1, and vitamin B12 +B9 substitution, with (arm B) or without bevacizumab (arm A), 15 mg/kg Q21D, for 6 cycles. Arm B nonprogressive patients received bevacizumab maintenance therapy until progression or toxicity. 445 patients to be recruited during a period 48 months, with at least 24 months of follow-up, and 385 events (deaths), will be needed to assure a power of 80% and detect at least a 4.3 months of median survival increase. This hypothesis leads to a Hazard Ratio (HR) of 1.33 and a 3-years survival of 14.7% in control arm and 23.6 % in experimental arm, with an absolute difference of 8.9% in survival rates. Accrual status: The first patient was included in February 2008. On January 31, 2012, 257 patients from 85 French centers had been enrolled. The end of accrual can be expected for September 2013. Ancillary studies: For molecular biomarker analyses, thoracoscopic tissue specimens (TS, ERCC1, MSH2, TUBB3, NF2, p16, RASSF1A methylation,15 microRNAs ) and blood samples (micro-RNAS, VEGF, osteopontin, SRMP) at diagnosis are centrally collected. Finally, a prospective study comparing PET-CT to standard CT with central blinded analysis, is currently on-going for evaluation of response, and accuracy of modified RECIST criteria for mesothelioma.