Patricia Martin

Epidermal Growth Factor Receptor targeting in non-small cell lung cancer: revisiting different strategies against the same target.

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the paradigm of treatment in non-small cell lung cancer (NSCLC). The molecular biology study of EGFR has led to clinical trials that select patients more accurately, regarding the presence of EGFR activating mutations. Nonetheless, a lack of response or a temporary condition of the response has been detected in patients on EGFR TKIs. This has urged to study potential resistance mechanisms underneath. The most important ones are the presence of secondary mutations in EGFR, such as T790M, or the overexpression of mesenchymal-epithelial transition factor (MET) that may explain why patients who initially respond to EGFR TKIs, may ultimately become refractory. Several approaches have been taken and new drugs both targeting EGFR resistance-mutation or MET are currently being developed. Here we review and update the EGFR biological pathway as well as the clinical data leading to approval of the EGFR TKIs currently in the market. New compounds under investigation targeting resistance mutations or dually targeting EGFR and other relevant receptors are also reviewed and discussed.

712PA THREE-STEP STRATEGY OF INDUCTION CHEMOTHERAPY, CHEMO-RADIOTHERAPY AND SURGERY IN LOCALLY ADVANCED PANCREATIC CANCER (LAPC) PATIENTS. ROLE OF A NONLINEAR MIXED EFFECTS MODELING TO PREDICT OUTCOME

ABSTRACT Aim: The optimal strategy for patients with LAPC remain a therapeutic challenge. A growing evidence suggests that both, pts with borderline resectable and unresectable tumors may benefit from a multimodal approach aimed at improving resectability and survival times. In the present work our experience after a long-term follow-up period is reported. Methods: From December 2005 to July 2011, 67 histologically confirmed LAPC, endoscopic ultrasound (EUS) staged T3-4 and/or N+ were retrospectively analysed. They received induction gemcitabine/oxaliplatin- based chemotherapy followed, in case of radiological response or stable disease, by chemo-radiotherapy (50.4 Gy concurrently with daily capecitabine and weekly oxaliplatin). Salvage surgery was performed when technically feasible. We have applied a nonlinear mixed effects (NLME) modeling to evaluate the impact of dynamic changes in tumor size, Ca- 19.9, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio on the clinical outcome of these patients. Results: The median age was 63 years (range 35-85). Male to female 36/31. Thirty eight pts (57%) completed the whole program (group A), whereas 27 (40%) received chemo and radioterapy but were not elegible for surgery (Group B). Two pts (3%) progressed after induction chemotherapy (Group C). EUS staged T4 or N+ was found in 20 (30%) and 24 (36%) respectively. Toxicity profile was mild, with no grade 4 toxicity being documented. On an intent to treat basis, R0 resection rate was 57%; ypT0ypN0 were observed in 11 (29%) of patients. Among resected patients, local and distant failure rates were 5% and 55%, respectively. The liver was the most frequent site of relapse 21(43%) pts. After a median follow up of 23 months (range 4 to 102), median PFS was 21, 10 and 1 month in groups A, B and C respectively (p = Conclusions: Our date suggest that this three-step strategy is feasible and active in LAPC patients. The NMLE population modeling will be presented at the meeting Disclosure: All authors have declared no conflicts of interest.