Crinò L, Dansin E, Garrido P, et al. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study
ABSTRACT 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.
Full-textDOI: · Available from: Yi-Long Wu, Sep 27, 2015
- SourceAvailable from: PubMed Central
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- "However, a clear long-term beneficial effect of bevacizumab maintenance therapy has not yet been confirmed. The present case was part of the SAiL (2) clinical trial, and the primary endpoint results suggested that bevacizumab combined with chemotherapy regimens may delay the time to progression (TTP) by 7.2–7.8 months and achieve 14.6–15.3 "
ABSTRACT: The safety of Avastin in lung cancer (SAiL) study is a multi-center, open-source, stand-alone study. Patients with untreated, locally advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered up to six cycles of chemotherapy combined with bevacizumab-humanized monoclonal antibodies, followed by maintenance therapy with bevacizumab until further progression of the disease. From August, 2006 to July, 2008 there were a total of 2,172 patients enrolled in the study, with a median progression-free survival time of 7.8 months and an overall survival time of 14.6 months. The present study describes the case of a 54-year-old male with lung cancer and T3N0M1 subcutaneous metastasis, which was initially treated with bevacizumab-combined carboplatin/paclitaxel (C/P) therapy and then maintained solely with bevacizumab for five years. Following six cycles of C/P bevacizumab treatment, the therapeutic evaluation revealed a stable disease (SD). The patient was kept on bevacizumab maintenance therapy for 50 months without disease progression until a persistent 3+ proteinuria was diagnosed in a follow-up review, which led to bevacizumab withdrawal and concomitant tumor growth. The present study concluded that the long-term application of bevacizumab monoclonal antibodies (mABs) was safe in a late-stage non-small cell lung cancer patient. The major adverse reaction that was exhibited was proteinuria, which was associated with the cumulative dose of bevacizumab and was able to be reversed by withdrawal. Patients with a prolonged SD may benefit from bevacizumab maintenance therapy.Oncology letters 12/2013; 6(6):1779-1783. DOI:10.3892/ol.2013.1603 · 1.55 Impact Factor
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- "In a phase IV trial bevacizumab-based therapy resulted in median OS of 14.6 months (95% CI 13.8–15.3) . Erlotinib is an EGFR TKI. "
ABSTRACT: Background: Molecularly targeted agents for non-small cell lung cancer (NSCLC) can provide similar efficacy to chemotherapy without chemotherapy-associated toxicities. Combining two agents with different modes of action could further increase the efficacy of these therapies. The TASK study evaluated the efficacy and safety of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with the anti-angiogenic agent bevacizumab as first-line therapy in unselected, advanced non-squamous NSCLC patients. Methods: Patients were recruited from December 2007 to September 2008. Planned sample size was 200 patients, a total of 124 patients were randomized. Patients were randomized using a minimization algorithm 1:1 to receive bevacizumab (iv 15 mg/kg day 1 of each 21-day cycle) plus chemotherapy (gemcitabine/cisplatin or carboplatin/paclitaxel standard doses, 4-6 cycles) (BC arm) or bevacizumab plus erlotinib (p.o. 150 mg/day; BE arm) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). If the hazard ratio (HR) of PFS for BE relative to BC was above 1.25 at the pre-planned interim analysis in favor of BC, the study would be re-evaluated. Secondary endpoints included overall survival, response rate and safety. Results: All randomized patients (n = 63 BE; n = 61 BC) were evaluated for the efficacy analyses. At the updated interim analysis, median PFS was 18.4 weeks (95% confidence interval [CI] 17.0-25.1) versus 25.0 weeks (95% CI 20.6-[not reached]) for BE versus BC, respectively (HR for death or disease progression, BE relative to BC, 2.05, p = 0.0183). The incidence of death was 19% for BE treatment compared with 11.5% for BC treatment. The HR for PFS at the updated interim analysis was above 1.25, therefore patients on the BE arm were permitted to change arms or switch to another drug and the study was terminated. Adverse events reported were as expected. Conclusions: The TASK study did not show a benefit in terms of PFS for the combination of erlotinib with bevacizumab in unselected first-line advanced non-squamous NSCLC compared with chemotherapy plus bevacizumab.Lung cancer (Amsterdam, Netherlands) 08/2013; 82(2). DOI:10.1016/j.lungcan.2013.08.002 · 3.96 Impact Factor
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- "We observed a median PFS of 5.4 months (compared with 6.2 and 6.5 months in the E4599 and AVAiL trials, respectively) and a median OS of 14.7 months (compared with 12.3 and >13 months in E4599 and AVAiL, respectively). In fact, the better comparator for our reported outcomes is the results of the SAiL phase IV trial, since they reflect the experience of community practice similar to that presented here, outside the rigidity of a phase III trial protocol. In the SAiL trial, the median OS was 14.6 months, which is very similar to our finding, and the time to tumor progression, which is usually longer than the PFS, was 7.8 months. "
ABSTRACT: Objectives Bevacizumab has been approved by the US Food and Drug Administration as a first-line therapy for metastatic non-small-cell lung cancer (NSCLC), in combination with carboplatin and paclitaxel. A single Latin American center experience was reviewed to determine the safety and efficacy of adding bevacizumab to first-line chemotherapy in a local population. Methods We retrospectively identified patients with non-squamous NSCLC treated with bevacizumab plus chemotherapy combinations as first-line chemotherapy between July 1, 2006, and January 30, 2011, at Sirio Libanes Hospital in Sao Paulo, Brazil. We collected data on patient characteristics, treatment combinations, toxicities, response to treatment, and survival. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis, and prognostic factors were identified by the Cox regression model. Results A total of 56 patients were included in the final analysis (median age 62.4 years; 70% male). In 35 patients (62.5%), bevacizumab was combined with carboplatin and paclitaxel, and in 16 patients (28.6%), it was combined with pemetrexed and carboplatin. The response rate evaluated by the reference clinical team reached 74.5%, the median PFS was 5.3 months, and the median OS was 14.8 months. In multivariate analysis, use of maintenance therapy was the only predictive factor for OS (hazard ratio 6.85, 95% confidence interval 2.94–15.22). No treatment-related deaths were identified, and the overall incidence of grade 3–4 non-hematologic toxicities was 16%. Conclusion Our results confirm the efficacy and safety data of bevacizumab first-line combinations for NSCLC in a Brazilian population.12/2012; 12(4). DOI:10.2165/11636760-000000000-00000