Motesanib Fails in a Phase III Trial for NSCLC

The gist: New research results have dashed hopes that a drug called motesanib (AMG 706) might be an effective treatment for Asian people with stage IV, non-squamous non-small cell lung cancer (NSCLC). In 2011, the drug failed testing in patients, but data showed there might be some benefit for certain Asian patients. Testing continued in a group of patients from Japan, South Korea, Taiwan, and Hong Kong. However, the new results show that motesanib does not improve standard treatment with the drugs paclitaxel and carboplatin.


Linifanib With Chemotherapy Delays Disease Worsening in Advanced Non-Squamous NSCLC

The gist: People with advanced non-squamous non-small cell lung cancer (NSCLC) might do better if a drug called linifanib is added to chemo treatment with the drugs carboplatin and paclitaxel. In a clinical trial with volunteer patients, people who took all three drugs went for several weeks longer without their disease worsening than patients who took only carboplatin and paclitaxel.

“The addition of linifanib to a carboplatin and paclitaxel regimen offered significantly improved progression-free survival (PFS) over placebo in a randomized phase II trial of patients with advanced non-squamous non–small-cell lung cancer (NSCLC).

“Previous work has shown that adding inhibitors of VEGF to standard chemotherapy can improve survival outcomes in advanced NSCLC. Linifanib (Abbott Laboratories) is a tyrosine kinase inhibitor with activity against VEGF and PDGF receptors. “Single-agent activity of linifanib in phase I and II clinical studies in patients with advanced NSCLC encouraged further evaluation of linifanib as a component of therapy for these patients,” wrote study authors led by Suresh S. Ramalingam, MD, of Winship Cancer Institute of Emory University in Atlanta…

“ ‘Although additional studies of linifanib in NSCLC are not currently planned, further evaluation of linifanib in patients with the identified biomarker signature is warranted,’ the authors concluded. ‘These findings are also of potential significance for other antiangiogenic agents presently under development for NSCLC.’ ”


Thymidylate Synthase Predicts Response to Chemo in NSCLC

The gist: Scientists have found that measuring a patient’s levels of a protein called thymidylate synthase (TS) could predict how well different kinds of chemotherapy might work for treating non-small cell lung cancer (NSCLC). Specifically, patients with low-levels of TS benefitted more from treatment with cisplatin plus pemetrexed than with cisplatin plus gemcitabine.

“A new phase II study suggests that expression of the enzyme thymidylate synthase (TS) can be used as a predictive marker for patients with non–small-cell lung cancer undergoing chemotherapy. Benefits of cisplatin plus pemetrexed over cisplatin plus gemcitabine were more pronounced in TS-negative patients than in TS-positive patients.

“ ‘Thymidylate synthase,’ said Myung-Ju Ahn, MD, of Sungkyunkwan University School of Medicine in Seoul, in a press release, ‘is targeted by pemetrexed, which is the most widely used chemotherapeutic regimen in the treatment of non-squamous NSCLC.’ Previous work has shown that the cisplatin/pemetrexed combination is superior to cisplatin/gemcitabine in non-squamous NSCLC, but levels of TS could predict the level of response.

“In this study, 315 non-squamous NSCLC patients were first stratified as either TS-positive (more than 10% of tumor cells express TS) or TS-negative, and then randomized to cisplatin plus either pemetrexed or gemcitabine. Results were presented at the European Society of Medical Oncology (ESMO) 2014 Congress in Madrid.

“The objective response rate in the cisplatin/pemetrexed patients who were TS-negative was 47%, compared with 21.1% in the cisplatin/gemcitabine group. In the TS-positive patients, meanwhile, the objective response rates were 40.3% for cisplatin/pemetrexed patients and 39.2% for cisplatin/gemcitabine patients (P = .008).”


Erlotinib Alone or with Bevacizumab as First-Line Therapy in Patients with Advanced Non-Squamous Non-Small-Cell Lung Cancer Harbouring EGFR Mutations (JO25567): An Open-Label, Randomised, Multicentre, Phase 2 Study

Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to compare two different treatment approaches for non-squamous non-small cell lung cancer (NSCLC) with mutations in the EGFR gene. One treatment combined the drugs erlotinib and bevacizumab, and the other treatment was simply erlotinib alone. Based on the results, the researchers say that erlotinib plus bevacizumab could be a new standard treatment for people with NSCLC with EGFR mutations.

“The authors aimed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non–squamous NSCLC with activating EGFR mutation–positive disease. Erlotinib plus bevacizumab combination could be a new first–line regimen in EGFR mutation–positive NSCLC. Further investigation of the regimen is warranted.”


ASCO 2014 Lung Cancer Roundup


Every year, thousands of people gather in Chicago, Illinois, for the American Society of Clinical Oncology (ASCO) Annual Meeting. The largest meeting of its kind, ASCO brings together doctors, researchers, nurses, patient advocates, pharmaceutical company representatives, and more to discuss the latest in cancer research. Here are some of the most exciting new developments in lung cancer research presented last week at ASCO 2014: Continue reading…


Phase II Trial of Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab Followed by Cetuximab and Bevacizumab in Advanced Nonsquamous Non-Small-Cell Lung Cancer: SWOG S0536

Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC.

 

This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.


Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous NSCLC

AVAPERL evaluated the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment. In an unselected population of patients with nonsquamous NSCLC who had achieved disease control with platinum-based chemotherapy plus bevacizumab, bevacizumab plus pemetrexed maintenance was associated with a significant PFS benefit compared with bevacizumab alone. The combination was well tolerated.


Efficacy of bevacizumab-containing chemotherapy for non-squamous non-small cell lung cancer with bone metastases

Skeletal-related events (SREs) negatively affect the quality of life of patients with cancer. Vascular endothelial growth factor receptor (VEGFR)-targeted therapy is effective against bone metastasis in animal models, but the clinical efficacy of anti-VEGFR inhibitors against bone metastases remains unclear. Therefore, we aimed to investigate the efficacy of chemotherapy with bevacizumab, an anti-VEGF antibody, against bone metastases.”


Avastin-Taxol Regimen May Be Effective Late-Line Treatment for Advanced Non-Squamous NSCLC

A retrospective study assessed the use of weekly bevacizumab (Avastin) along with paclitaxel (Taxol) every 3 weeks in patients with advanced non-squamous, non-small cell lung cancer (NSCLC) who had previously received at least three rounds of treatment. The Avastin-Taxol combination was found to be an effective antitumor treatment. Some patients experienced serious side effects, including one death. However, overall toxicity was deemed acceptable compared to typical chemotherapy results in similar patients.