A Randomized Phase II Trial of Pemetrexed/Gemcitabine/Bevacizumab or Pemetrexed/Carboplatin/Bevacizumab in the First-Line Treatment of Elderly Patients with Advanced Non-small Cell Lung Cancer

Spigel, David R.; Hainsworth, John D.; Shipley, Dianna; Ervin, Thomas J.; Köhler, Peter; Lubiner, Eric T.; Peyton, James D.; Waterhouse, David; Burris, Howard A.; Greco, F. Anthony

doi:10.1097/jto.0b013e3182307efe

Cited by 26 publications

(10 citation statements)

References 31 publications

(25 reference statements)

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“…Similarly, a phase II study randomized 192 patients with stage IIIB or IV NSCLC to receive erlotinib 150 mg and pazopanib 600 mg daily or erlotinib and placebo, following one to two lines of chemotherapy [ 41 ]. The combination regimen obtained a significant improvement of PFS (2.6 versus 1.8 months, HR 0.59, 95% CI: 0.43–0.83, p = 0.0016), but no advantage in OS (6.8 versus 6.7 months, HR 1.1, 95% CI: 0.77–1.55, p = 0.61).…”

Section: Sunitinib Sorafenib Vandetanibmentioning

confidence: 99%

Angiogenesis Inhibitors in NSCLC

Manzo

Montanino

Carillio

et al. 2017

IJMS

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Angiogenesis is a complex biological process that plays a relevant role in sustaining the microenvironment, growth, and metastatic potential of several tumors, including non-small cell lung cancer (NSCLC). Bevacizumab was the first angiogenesis inhibitor approved for the treatment of patients with advanced NSCLC in combination with chemotherapy; however, it was limited to patients with non-squamous histology and first-line setting. Approval was based on the results of two phase III trials (ECOG4599 and AVAIL) that demonstrated an improvement of about two months in progression-free survival (PFS) in both trials, and in the ECOG4599 trial, an improvement in overall survival (OS) also. Afterwards, other antiangiogenic agents, including sunitinib, sorafenib, and vandetanib have been unsuccessfully tested in first and successive lines. Recently, two new antiangiogenic agents (ramucirumab and nintedanib) produced a significant survival benefit in second-line setting. In the REVEL study, ramucirumab plus docetaxel prolonged the median OS of patients with any histology NSCLC when compared with docetaxel alone (10.4 versus 9.1 months, hazard ratio (HR) 0.857, p = 0.0235). In the LUME-Lung 1 study, nintedanib plus docetaxel prolonged the median PFS of patients with any tumor histology (p = 0.0019), and improved OS (12.6 versus 10.3 months) in patients with adenocarcinoma. As a result, it became a new option for the second-line treatment of patients with advanced NSCLC and adenocarcinoma histology. Identifying predictive biomarkers to optimize the benefit of antiangiogenic drugs remains an ongoing challenge.

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Section: Sunitinib Sorafenib Vandetanibmentioning

confidence: 99%

Angiogenesis Inhibitors in NSCLC

Manzo

Montanino

Carillio

et al. 2017

IJMS

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“…The selection process is summarized in Figure 1. In total, 6,433 patients were investigated in these trials and they had a variety of cancers: NSCLC (twelve trials) [19], [20], [23], [32], [33], [34], [35], [36], [37], [38], [39], [40], breast cancer (three trials) [24], [41], [42], pancreatic cancer (three trials) [13], [43], [44], bladder cancer (one trial) [21], Carcinoma of unknown (one trial) [45]. All included trials involved randomized treatment allocation.…”

Section: Resultsmentioning

confidence: 99%

Increased Risk of High-Grade Hemorrhage in Cancer Patients Treated with Gemcitabine: A Meta-Analysis of 20 Randomized Controlled Trials

Wang

Tao

et al. 2013

PLoS ONE

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PurposeGemcitabine, a third-generation anticancer agent, has been shown to be active in several solid tumors. High-grade hemorrhage (grade≥3) has been reported with this drug, although the overall risk remains unclear. We conducted a meta-analysis of randomized controlled trials evaluating the incidence and risk of high-grade hemorrhage associated with gemcitabine.MethodsPubmed was searched for articles published from January 1, 1990 to December 31, 2012. Eligible studies included prospective randomized controlled phase II and III trials evaluating gemcitabine-based vs non-gemcitabine-based therapy in patients with solid tumors. Data on high-grade hemorrhage were extracted. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of included trials.ResultsA total of 6433 patients from 20 trials were included. Among patients treated with gemcitabine-based chemotherapy, the overall incidence of high-grade hemorrhage was 1.7% (95%CI: 0.9–3.1%), and the RR of high-grade hemorrhage was 2.727 (95%CI: 1.581–4.702, p<0.001). Exploratory subgroup analysis revealed the highest RR of hemorrhage in non-small-cell lung cancer (NSCLC) patients (RR: 3.234; 95%CI, 1.678–6.233; p<0.001), phase II trials (RR 7.053, 95%CI: 1.591–31.27; p = 0.01), trials reported during 2006–2012 (RR: 3.750; 95%CI: 1.735–8.108, p<0.001) and gemcitabine used as single agent (RR 7.48; 95%CI: 0.78–71.92, p = 0.081).ConclusionGemcitabine is associated with a significant increase risk of high-grade hemorrhage in patients with solid tumors when compared with non-gemcitabine-based therapy.

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“…The presented cases demonstrated significant clinical efficacy with mild adverse effects. The clinical activity of this regimen as the first-line treatment for elderly patients with non-squamous NSCLC was recently reported [7]. We think this regimen might be a viable treatment option even after heavy treatment such as platinum-containing chemotherapy, especially for relatively young patients with preserved organ function and good performance status.…”

Section: Discussionmentioning

confidence: 97%

Successful Treatment with Pemetrexed, Carboplatin, and Bevacizumab for Platinum-Resistant Adenocarcinoma of the Lung

Wada

Fujimoto

Gemba

et al. 2012

Case Reports in Oncological Medicine

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We present two cases of relapsed adenocarcinoma of the lung: a 50-year-old male and a 67-year-old male. Both patients had previously been treated with platinum-containing systemic chemotherapy. In both cases, significant clinical efficacy was demonstrated with combination chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab as salvage treatment. Adverse events were mild. This regimen might be a viable therapeutic option even after heavy treatment such as platinum-containing chemotherapy, especially for patients with preserved organ function and good performance status.

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A Randomized Phase II Trial of Pemetrexed/Gemcitabine/Bevacizumab or Pemetrexed/Carboplatin/Bevacizumab in the First-Line Treatment of Elderly Patients with Advanced Non-small Cell Lung Cancer

Abstract: Treatment with pemetrexed/carboplatin/bevacizumab was associated with improved TTP and OS in this elderly population and should be further evaluated. Treatment-related toxicities were expected and usually manageable, although deaths occurred with both regimens.

Cited by 26 publications

References 31 publications

Angiogenesis Inhibitors in NSCLC

Angiogenesis Inhibitors in NSCLC

Increased Risk of High-Grade Hemorrhage in Cancer Patients Treated with Gemcitabine: A Meta-Analysis of 20 Randomized Controlled Trials

Successful Treatment with Pemetrexed, Carboplatin, and Bevacizumab for Platinum-Resistant Adenocarcinoma of the Lung

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