A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer

Ciuleanu, Tudor-Eliade; Tsai, Chun Ming; Tsao, Chao Jung; Milanowski, Janusz; Amoroso, Domenico; Heo, Dae Seog; Groen, Harry J.M.; Szczęsna, Aleksandra; Chung, Chen-Yen; Chao, Tsu‐Yi; Middleton, Gary; Zeaiter, Ali; Klingelschmitt, Gaëlle; Klughammer, Barbara; Thatcher, Nick

doi:10.1016/j.lungcan.2013.08.002

Cited by 34 publications

(38 citation statements)

References 29 publications

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“…The TASK trial showed a second-line proportion of 49% after first-line EB [11]. The SAKK (Swiss Group for Clinical Cancer Research) reported on a fixed-sequence protocol with initial EB treatment, showing a higher starting proportion in second-line treatment (62 (61%) out of 101) but a substantial drop down for those receiving four cycles or more (35 (35%) out of 101) [17].…”

Section: Discussionmentioning

confidence: 99%

“…The DSMB reviewed the study performance at regular intervals. When unfavourable results emerged in the TASK trial (a study of tarceva (erlotinib) in combination with avastin (bevacizumab) in patients with advanced NSCLC) [11], which used similar comparators, the DSMB reviewed current, interim efficacy data from the INNOVATIONS trial and indicated no reason to stop the trial. The study was conducted in accordance with the Declaration of Helsinki (version 1996) and the applicable ICH-GCP (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Good Clinical Practice) guidelines.…”

Section: Introductionmentioning

confidence: 99%

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Erlotinib and bevacizumabversuscisplatin, gemcitabine and bevacizumab in unselected nonsquamous nonsmall cell lung cancer

et al. 2015

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Erlotinib with bevacizumab showed promising activity in recurrent nonsquamous (NS) nonsmall cell lung cancer (NSCLC). The INNOVATIONS study was designed to assess in first-line treatment of unselected cisplatin-eligible patients this combination compared to cisplatin, gemcitabine and bevacizumab.Stage IIIB/IV patients with NS-NSCLC were randomised on erlotinib (150 mg daily) and bevacizumab (15 mg·kg −1 on day 1, every 3 weeks) (EB) until progression, or cisplatin (80 mg·m −2 on day 1, every 3 weeks) and gemcitabine (1250 mg·m −2 on days 1 and 8, every 3 weeks) up to six cycles and bevacizumab (15 mg·kg −1 on day 1, every 3 weeks) (PGB) until progression. 224 patients were randomised (EB n=111, PGB n=113). The response rate (12% versus 36%; p<0.0001), progression-free survival (median 3.5 versus 6.9 months; hazard ratio (HR) 1.85, 95% CI 1.39-2.45; p<0.0001) and overall survival (median 12.6 versus 17.8 months; HR 1.41, 95% CI 1.01-1.97; p=0.04) clearly favoured PGB. In patients with epidermal growth factor receptor mutations (n=32), response rate, progression-free survival and overall survival were not superior with EB.Platinum-based combination chemotherapy remains the standard of care in first-line treatment of unselected NS-NSCLC. Molecular targeted approaches strongly mandate appropriate testing and patient selection. @ERSpublications Platinum-based combination chemotherapy remains the standard of care in first-line treatment of unselected NS-NSCLC http://ow.ly/ITkNj

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Erlotinib and bevacizumabversuscisplatin, gemcitabine and bevacizumab in unselected nonsquamous nonsmall cell lung cancer

et al. 2015

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“…Bevacizumab in combination with 5-fluorouracilbased chemotherapy has been approved as first/second line therapy for advanced colorectal cancer (CRC) and in combination with carboplatin and/or paclitaxel has been approved as first line therapy for advanced non-small cell lung cancer (NSCLC). [18][19][20][21] The success of bevacizumab can be attributed to its sustained target inhibition resulted from its long half-life and good safety profile due to its high specificity allowing it to combine with a variety of chemotherapies. However, bevacizumab has its limitations in the clinic, such as its intravenous dosing, immunogenicity and potential to induce autoimmune diseases after long term treatment.…”

Section: Introductionmentioning

confidence: 99%

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy

Sun¹,

Zhou²,

Zhang³

et al. 2014

Cancer Biology & Therapy

103

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“…In a double-blind, placebo-controlled, phase 3 trial, this combination regimen significantly prolonged PFS in patients with recurrent or refractory NSCLC compared with the effects of Erl alone (median 3.4 vs 1.7 months; HR=0.62, 95% CI 0.52 to 0.75) 13. However, a contradictory result was obtained in another phase 2 study, in which the combination therapy shortened PFS compared with Bev+CT (BC; 18.4 vs25.0 months; HR=2.05, 95% CI 1.11 to 3.77) 14. The treatment line might affect the efficacy of Bev and Erl.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis

et al. 2016

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ObjectivesBevacizumab and erlotinib inhibit different tumour growth pathways, and both exhibit beneficial effects in the treatment of non-small-cell lung cancer (NSCLC). However, the efficacy of bevacizumab in combination with erlotinib remains controversial. Therefore, we conducted a meta-analysis to compare combination treatment with bevacizumab and erlotinib to bevacizumab or erlotinib monotherapy in the treatment of NSCLC.MethodsRandomised controlled trials (RCTs) published in PubMed, Web of Science and EMBASE were systematically reviewed. The main outcome measures included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and adverse events. Results were expressed as HRs or risk ratios (RRs) with 95% CIs.Results5 RCTs involving a total of 1736 patients were included in this meta-analysis. The combination of bevacizumab and erlotinib significantly improved PFS (HR=0.63, 95% CI 0.53 to 0.75; p=0.000) and the ORR (RR=1.91, 95% CI 1.19 to 3.06; p=0.007) in the second-line treatment of NSCLC compared with bevacizumab or erlotinib alone. However, no significant difference in OS was observed between the combination and monotherapy groups (HR=0.96, 95% CI 0.83 to 1.11; p=0.573). A subgroup analysis has shown that the greatest PFS benefit was associated with an age of <65 years(HR=0.74, 95% CI 0.57 to 0.96; p=0.026), Asian/Pacific Islander ethnicity (HR=0.23, 95% CI 0.10 to 0.54; p=0.001), Eastern Cooperative Oncology Group performance status (ECOG PS) 1 (HR=0.82, 95% CI 0.68 to 0.98; p=0.033), stage IIIB or IV disease (HR=0.68, 95% CI 0.57 to 0.82; p=0.000) and no history of smoking (HR=0.48, 95% CI 0.32 to 0.71; p=0.000). The incidence of grade 3/4 adverse events such as rash and diarrhoea was higher in the combination group than in the monotherapy group.ConclusionsThe addition of bevacizumab to erlotinib can significantly improve PFS and the ORR in the second-line treatment of NSCLC with an acceptable and manageable risk of rash and diarrhoea. Further well-conducted, large-scale trials are needed to validate these findings.

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A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer

Abstract: 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.

Cited by 34 publications

References 29 publications

Erlotinib and bevacizumabversuscisplatin, gemcitabine and bevacizumab in unselected nonsquamous nonsmall cell lung cancer

Erlotinib and bevacizumabversuscisplatin, gemcitabine and bevacizumab in unselected nonsquamous nonsmall cell lung cancer

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy

Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis

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