moreover, BRAF V600E was detected in 3% variant allelic frequency (Fig. 1A). The presence of BRAF V600E mutations was confirmed by amplification refractory mutation system polymerase chain reaction in plasma collected in March but not detected in January (Fig. 1B). These data provide confirmation of the role of BRAF V600E as a mechanism of escape after a third-generation EGFR tyrosine kinase inhibitor and suggest that liquid biopsy is suitable for detecting new molecular data regarding resistance. There was a consistency between progression as seen on CT scan and clinically and the presence of BRAF V600E in the cfDNA.The course of disease with this new oncogenic transformation was clinically very aggressive.
Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this protocol in ongoing trials and the association of cisplatin, docetaxel, and cetuximab appears to be the most efficient. The human papilloma virus is very likely a favorable prognostic factor. Immunotherapy with nivolumab or pembrolizumab is now a new standard of treatment in second line after yielding an improvement in overall survival, but predictive markers of efficacy are needed to refine the selection of patients. The combination of paclitaxel and buparlisib appears to be promising.
Concomitant chemotherapy with cisplatin (100 mg/m every 3 weeks) improves outcome for high-risk patients in the postoperative setting and for inoperable disease. Toxicity is increased. Other schemes of potentiation are sometimes used to reduce toxicity, but efficiency is diminished. Cetuximab also improves outcome, but there has been no direct comparison with cisplatin. Immunotherapy is currently being evaluated in association with radiation therapy. Trials are ongoing to evaluate the impact of de-escalation for human papillomavirus-positive patients. The association of docetaxel, cisplatin, and 5-fluorouracil is the standard of induction; it is also the standard treatment for laryngeal preservation. Many trials have attempted to compare the concomitant approach with the sequential treatment; none have managed to show a difference between the two. After induction chemotherapy, there is still no standard of potentiation of radiotherapy.
Angiogenesis is critical for tumor growth, proliferation and metastasis with the crucial role of Vascular Endothelial Growth factor (VEGF) pathway. Ramucirumab is a monoclonal antibody that specifically targets the extracellular domain of Vascular Endothelial Growth Factor Receptor 2. Areas covered: We performed a search on Medline to browse the current literature on Ramucirumab and anti-angiogenic agents, for the treatment of NSCLC. The REVEL study demonstrated a significant improvement of response rate, progression-free survival and overall survival by adding ramucirumab to docetaxel compared to docetaxel plus a placebo in second-line treatment of advanced non-small cell lung cancer, irrespective of histology, with an acceptable safety profile. This article has for objective to summarize efficacy and safety data of the use of ramucirumab in combination with docetaxel in second line in NSCLC. Expert commentary: REVEL constitutes the first significant advance in second-line setting for patients eligible to anti-angiogenic therapy. The landscape of post-platinum therapy in NSCLC is considerably evolving and the role of ramucirumab or other anti-angiogenic agents as nintedanib in this setting has to be discussed for each patient with other available treatment options, among which immune checkpoints inhibitors, as well as the best treatment sequence.
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