Treatment Paradigms for Patients with Metastatic Non-Small Cell Lung Cancer, Squamous Lung Cancer: First, Second, and Third-Line

Al-Farsi, Abdulaziz; Ellis, Peter

doi:10.3389/fonc.2014.00157

Cited by 40 publications

(27 citation statements)

References 29 publications

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“…Currently, 'continuation' or 'switch maintenance' for non-progressive disease after frontline therapy is the recommended alternative for patients with good performance status [13][14][15][16][17]. 'Continuation maintenance' implies that a chemotherapy or biological that was part of the initial platinum-based therapy is continued.…”

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confidence: 99%

“…Alternatively, switch maintenance means that a third agent is initiated prior to Vaccine Profile evidence of disease progression after completion of platinumbased therapy [13][14][15][16][17]. Several drugs used as maintenance only improve the progression-free survival, while agents like pemetrexed or erlotinib also increase the overall survival of the non-squamous NSCLC patients [13][14][15][16][17]. Two antibodies targeting EGFR, cetuximab and necitumumab, were evaluated in Phase III studies in advanced NSCLC patients.…”

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confidence: 99%

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CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer

Ramos

Rodríguez

Vinageras

et al. 2015

Expert Review of Vaccines

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Epidermal growth factor receptor (EGFR) is overexpressed in many epithelial tumors and its role in the development of non-small-cell lung cancer (NSCLC) is widely documented. CIMAvax-EGF is a therapeutic cancer vaccine composed by recombinant EGF conjugated to a carrier protein and emulsified in Montanide ISA51. Vaccination induces antibodies against self-EGF that block EGF-EGFR interaction and inhibit EGFR phosphorylation. Five clinical trials were conducted to optimize vaccine formulation and schedule. Then, two randomized studies were completed in advanced NSCLC, where CIMAvax-EGF was administered after chemotherapy, as 'switch maintenance'. The vaccine was very well tolerated and the most frequent adverse events consisted of grade 1/2 injection site reactions, fever, headache, vomiting and chills. CIMAvax was immunogenic and EGF concentration was reduced after vaccination. Subjects receiving a minimum of 4 vaccine doses had a significant survival advantage. NSCLC patients with high EGF concentration at baseline had the largest benefit, comparable with best maintenance therapies.

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confidence: 99%

Section: Please Scroll Down For Articlementioning

confidence: 99%

CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer

Ramos

Rodríguez

Vinageras

et al. 2015

Expert Review of Vaccines

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“…The most common preoperative treatment option for patients with NSCLC is chemotherapy, including first-line, second-line or third-line treatments [3,4]. Up to now, unlike the availability of many single or combined reagents for first-line chemotherapy, only limited choices of chemotherapy reagents are available for standard second-line settings, namely three single chemotherapy reagents: docetaxel, pemetrexed and erlotinib, that had been approved by the Food and Drug Administration (FDA) in the USA to treat NSCLC patients with prior failed first-line chemotherapy [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

A phase II clinical study of using nab-paclitaxel as second-line chemotherapy for Chinese patients with advanced non-small cell lung cancer

Zhang

2015

Med Oncol

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The aim of this clinical study was to evaluate the efficacy and safety of nab-paclitaxel to treat patients with advanced non-small cell lung cancer (NSCLC) who failed first-line chemotherapy. Eligible patients had advanced NSCLC and had been treated with first-line platinum-based chemotherapy but still had disease progression. Patients received nab-paclitaxel 100 mg/m(2) (i.v.) on days 1, 8 and 15 of a 28-day cycle. Primary endpoint is 6-month progression-free survival (PFS). Fifty-six patients with advanced NSCLC were enrolled in the study (55.4 % male patients, 44.6 % female patients; median age 59.6 years; ranging from 32 to 83 years). Six-month PFS rate was 18 % (95 % CI 7.8-28.7 %). Median PFS was 3.5 months (95 % CI 1.9-5.8 months). Median overall survival was 6.8 months (95 % CI 4.7-9.3 months). No complete responses were achieved. Overall response rate was 16.1 % (95 % CI 8.9-24.7 %). Grade 3 or 4 adverse events (AEs) were observed in patients receiving nab-paclitaxel. The most common grade 3 or 4 AEs were dizziness, pulmonary embolism and fatigue. Nab-paclitaxel showed clinically equivalent efficacy on patients' survivals and response rates, as compared with other FDA-approved second-line chemotherapy agents. Given the tolerability on grade 3 or 4 adverse events, nab-paclitaxel may be considered an alternative second-line treatment option for NSCLC.

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“…As a result of the above therapeutic limitations, standard chemotherapy regimens for squamous NSCLC (sqNSCLC) consist of a platinum agent and gemcitabine, paclitaxel, or vinorelbine as first-line therapy and docetaxel in the secondline setting [10]. Given the limited efficacy of conventional chemotherapies, however, therapeutic alternatives in squamous cell carcinoma of the lung have been investigated, including agents targeting epidermal growth factor receptor (EGFR).…”

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Inhibition in the Management of Squamous Cell Carcinoma of the Lung

Goss

Spaans

2016

The Oncologist

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Molecular therapies targeting epidermal growth factor receptor (EGFR) have had a profound impact on the management of advanced non-small cell lung cancer (NSCLC). EGFR inhibition with EGFR tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR monoclonal antibodies (mAbs) in squamous NSCLC (sqNSCLC) remains controversial in patients whose tumors are not known to harbor EGFR mutations. Recent meta-analyses of EGFR-inhibition randomized trials that are adequately powered for histological subgroup analysis and anti-EGFR trials limited to patients with squamous histology afford the opportunity to revisit EGFR treatment in sqNSCLC. In unselected patients with sqNSCLC who are not eligible for chemotherapy, EGFR-TKI therapy is a valid treatment option over placebo or best supportive care, with improved progression-free survival noted in randomized controlled trials in both the first-and second-line setting and improved overall survival (OS) in the second-line setting. In patients eligible for chemotherapy, first-line combination regimens with anti-EGFR mAbs have been shown to improve OS over chemotherapy alone in patients with squamous histology in meta-analysis and more recently in the SQUIRE sqNSCLC trial (chemotherapy with and without necitumumab).In sqNSCLC patients who respond to induction chemotherapy, maintenance therapy with erlotinib delays disease progression and may improve the survival of patients with stable disease. In the second-line setting, survival outcomes are comparable between chemotherapy and EGFR-TKIs in meta-analysis, with the latter being more tolerable as a second-line therapy. Newer-generation EGFR-TKI therapies may further benefit patients with sqNSCLC who have failed first-line chemotherapy, given the positive trial results from LUX-Lung 8 (afatinib vs. erlotinib). EGFR is a valid therapeutic target in unselected/EGFR wild-type patients with squamous cell carcinoma of the lung. With the recent approval of immune checkpoint inhibitors in the second-line management of advanced sqNSCLC and their adoption as a new standard of care, there exists an opportunity for novel combination therapies to increase therapeutic efficacy and durable tumor control. As more targeted agents are approved, combination regimens that include an anti-EGFR agent should be evaluated, and the optimal sequencing of targeted therapies should be defined. The Oncologist 2016; 21:205-213Implications for Practice: Anti-epidermal growth factor receptor (EGFR) therapies remain controversial in unselected/wild-type EGFR squamous non-small cell lung cancer (NSCLC). Recent meta-analyses and squamous-only NSCLC EGFR-inhibition trials have overcome the power limitations of early trials and can now inform the management of squamous NSCLC with anti-EGFR therapies. With the approval of immunotherapeutics in the second-line management of squamous NSCLC, there exists an opportunity for novel combination therapies to improve efficacy and durable tumor control. The optimal timing and sequencing of available second-line targeted thera...

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Treatment Paradigms for Patients with Metastatic Non-Small Cell Lung Cancer, Squamous Lung Cancer: First, Second, and Third-Line

Cited by 40 publications

References 29 publications

CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer

CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer

A phase II clinical study of using nab-paclitaxel as second-line chemotherapy for Chinese patients with advanced non-small cell lung cancer

Epidermal Growth Factor Receptor Inhibition in the Management of Squamous Cell Carcinoma of the Lung

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