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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Recent advances in the treatment of non-small cell and small cell lung cancer
1University of North Carolina at Chapel Hill 170 Manning Drive, Physician's Office Building, 3rd Floor, Chapel Hill, NC 27599-7305 USA.
Abstract:
Recent presentations at the American Society of Clinical Oncology (ASCO) meeting from 30 May to 3 June, 2014, will impact routine clinical care and the development of clinical trials in non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (ES-SCLC). Patients with activating epidermal growth factor receptor (EGFR) mutations, defined as exon 19 and exon 21 L858R point mutations, experience a high objective response rate and prolonged progression-free survival with EGFR tyrosine kinase inhibitors. However, inevitably, patients experience disease progression and the most common mechanism of acquired resistance is an EGFR exon 20 T790M mutation. Several agents (AZD9291, CO-1686 and HM61713) have demonstrated impressive activity in patients with T790M resistance mutations. Additional data on the efficacy of first-line therapy with afatinib and the combination of erlotinib and bevacizumab for patients with EGFR mutant NSCLC were presented. The results of a phase III trial of crizotinib compared to platinum-pemetrexed in the first-line setting, and a phase I trial and expansion cohort of ceritinib, provided additional efficacy and toxicity data for patients with anaplastic lymphoma kinase rearranged NSCLC. A phase III trial of cisplatin and gemcitabine, with and without necitumumab, revealed an improvement in overall survival with the addition of necitumumab in patients with squamous NSCLC. In the second-line setting, a phase III trial of docetaxel with ramucirumab or placebo revealed an improvement in overall survival with the addition of ramucirumab. In extensive stage small cell lung cancer phase III trials of consolidative thoracic radiation therapy and prophylactic cranial radiation failed to reveal an improvement in overall survival.
Insights
New lung cancer treatments show promise. Epidermal growth factor receptor (EGFR) inhibitors benefit EGFR-mutated non-small cell lung cancer (NSCLC), while new agents target T790M resistance mutations. Anaplastic lymphoma kinase (ALK) inhibitors and additions to chemotherapy also show efficacy.
Area of Science:
- Medical Oncology
- Clinical Trials
- Translational Research
Background:
- Activating epidermal growth factor receptor (EGFR) mutations (exon 19, exon 21 L858R) in non-small cell lung cancer (NSCLC) respond well to EGFR tyrosine kinase inhibitors (TKIs).
- Acquired resistance, often via EGFR T790M mutation, limits TKI efficacy.
- Anaplastic lymphoma kinase (ALK) rearrangements and squamous histology are other NSCLC subtypes with distinct treatment landscapes.
Purpose of the Study:
- To summarize key clinical trial data presented at the 2014 American Society of Clinical Oncology (ASCO) meeting.
- To highlight advancements in targeted therapies and chemotherapy for NSCLC and extensive stage small cell lung cancer (ES-SCLC).
- To inform clinical practice and future trial design in lung cancer.
Main Methods:
- Review of clinical trial results presented at the 2014 ASCO meeting.
- Analysis of data on targeted agents (EGFR TKIs, ALK inhibitors) and chemotherapy combinations.
- Evaluation of outcomes including objective response rate, progression-free survival, and overall survival.
Main Results:
- New agents (AZD9291, CO-1686, HM61713) show activity against EGFR T790M resistance mutations.
- First-line afatinib and erlotinib/bevacizumab data for EGFR-mutant NSCLC were presented.
- Crizotinib and ceritinib data for ALK-rearranged NSCLC were updated.
- Necitumumab improved overall survival in squamous NSCLC when added to cisplatin/gemcitabine.
- Ramucirumab improved overall survival in second-line NSCLC when added to docetaxel.
- Consolidative thoracic radiation and prophylactic cranial radiation did not improve survival in ES-SCLC.
Conclusions:
- Targeted therapies continue to evolve for EGFR-mutant and ALK-rearranged NSCLC, with emerging options for resistance.
- Chemotherapy combinations, like cisplatin/gemcitabine with necitumumab, offer survival benefits in specific NSCLC subtypes.
- Second-line ramucirumab improves survival in NSCLC.
- Current radiation strategies do not enhance survival in ES-SCLC.
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