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The review also emphasizes the urgent need for reliable biomarkers to guide therapeutic decision-making and outlines prospective changes to the second-line landscape with some of the current second-line treatment concepts likely to be moved to the first-line.

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Drug reimbursement is bound to the presence of a common activating EGFR mutation i. However, the relevance of EGFR mutations for the second-line decision-making process remained less clear, and erlotinib for all NSCLC as well as afatinib for squamous cell histology only have initially been FDA-approved irrespective of EGFR mutational status or other predictive markers 3Three er bb nail.

Both drugs demonstrated promising activity against TM in preclinical models but failed to overcome TM-mediated resistance in patients due to dose-limiting toxicity resulting from inhibition of wild-type EGFR Currently, treatment paradigms are most dramatically changing in tumors with squamous cell histology.

Reflecting the tobacco carcinogenesis, tumors are genomically complex yet EGFR mutations are sporadic, and EGFR molecular testing is not routinely performed in this subgroup Molecular analyses indicated that pan-ErbB blockade could be of therapeutic benefit in squamous cell tumors due to multiple genetic aberrations in ErbB receptors HER2: This approval is irrespective of the intratumoral EGFR mutational status.

Supposedly, the improved OS [median 7.

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