KI) therapy has proven worth in patients with advanced non-small cell lung cancer. Outcomes of the JBR.21 study demonstrated a survival advantage for erlotinib versus best supportive care within the second- or third-line therapy of sophisticated non-small cell lung cancer, top to the approval of erlotinib for this indication [1]. It was later found that EGFR TKI therapy is of distinct benefit for any subset of patients with tumors harboring activating EGFR gene mutations, including exon 19 deletions and exon 21 L858R gene mutations. Primarily based onCorrespondence:AfshinDowlati,M.D.,DepartmentofMedicine,UniversityHospitalsCaseMedicalCenter,CaseWesternReserveUniversity,11100Euclid Avenue, Cleveland, Ohio 44106, USA. Telephone: 216-844-5181; E-Mail: [email protected]; or Balazs Halmos, M.D., Division of Hematology/Oncology, Herbert Irving Extensive Cancer Center, New York Presbyterian Hospital-Columbia University Medical Center, 161 Fort Washington Avenue, New York, New York 10032, USA.Telephone: 212-305-8574; E-Mail: [email protected] Received April 1, 2015; accepted for publication July 2, 2015; published On-line First on August 25, 2015. �AlphaMed Press 1083-7159/2015/ 20.00/0 Oncologist 2015;20:1298sirtuininhibitor303 www.TheOncologist�AlphaMed PressHalmos, Pennell, Fu et al. a series of randomized research demonstrating enhanced response prices and progression-free survival with EGFR TKI therapy (erlotinib, gefitinib, and afatinib) when compared with frontline chemotherapy, frontline EGFR TKI therapy has turn into the standard ofcare for this molecularly defined subgroup of patients [2].TGF alpha/TGFA, Human (CHO) Despite the constant benefit of EGFR TKI therapy in EGFRmutated lung cancer, illness progression is uniform and acquired resistance is usually a key clinical difficulty [3, 4].LILRA2/CD85h/ILT1 Protein Gene ID It remains unclear irrespective of whether continuation of EGFR TKI therapy in the time of illness progression is of advantage, but, in practice, it is actually frequently pursued, analogous to continuing antiandrogen or trastuzumab therapy beyond progression in prostate and ErbB2-positive breast cancer [5, 6]. At the time of progression, each and every patient likely harbors various tumor clones, for example ones with acquired resistance mechanisms responsible for the observed illness progression on imaging, too as other clones that stay sensitive and suppressed by way of EGFR TKI therapy.PMID:23912708 Continued suppression of those clones could theoretically yield clinical rewards by way of EGFR TKI therapy beyond progression. Moreover, anecdotal clinical observations suggestive of speedy tumor flares upon cessation of targeted therapy in about 20 with the patients have added for the typical acceptance in clinical practice of continuing EGFR TKI therapy beyond progression [7]. Nevertheless, pharmacodynamic interactions, added toxicity, and expenses, as well as high-level molecular resistance, which includes the improvement of acquired T790M mutations, might limit the benefit of continued EGFR TKI therapy with a reversible EGFR TKI for instance erlotinib [8]. In spite of the intriguing basis for continued EGFR TKI therapy upon progression and its use in clinical practice, we continue to lack evidence of a clinical advantage from such an method. Provided the monetary charges and linked toxicities of TKI therapy, randomized trials evaluating the function of continuing these drugs beyond progression are desperately needed. In 2007, we initiated a randomized phase II study to assess the possible benefit for continued EGFR TKI ther.