J. de Castro Carpeño

Analysis of the Concordance in the EGFR Pathway Status Between Primary Tumors and Related Metastases of Colorectal Cancer Patients:Implications for Cancer Therapy

Patients with metastatic Colorectal Cancer (mCRC), in which primary tumors are KRAS mutated, have no response to anti-EGFR therapy. However, less than half of mCRC patients with KRAS wild-type primary tumors respond to anti-EGFR therapy. Other downstream effectors of the EGFR pathway are being analyzed to fine-tune KRAS predictive value. However, as the primary tumor is the tissue of analysis that determines the use of anti-EGFR therapy in advanced disease, a high concordance in the status of these effectors between primary tumors and related metastases is required. We analyzed the concordances of downstream EGFR effectors in tumoral pairs of primaries and related metastases in a series of KRAS wild-type patients. One hundred seventeen tumoral pairs from patients with CRC were tested for KRAS mutational status. The level of concordance in the presence of KRAS mutations was 91% between the primary tumor and related metastases. The 70 pairs with KRAS wild-type primary tumors were further analyzed for BRAF and PIK3CA mutational status and for EGFR, PTEN and pAKT expression, and the number of concordant pairs was 70 (100%), 66 (94%), 43 (61%), 46 (66%) and 36 (54%), respectively. Our findings suggest that the mutational status of KRAS, BRAF and PIK3CA in the primary tumor is an adequate surrogate marker of the status in the metastatic disease. On the other hand, the immunohistochemical analysis of EGFR, PTEN and pAKT showed a much higher degree of discordance between primaries and related metastases.

1252PNSCLC PATIENTS WITH BRAIN METASTASES TREATED WITH PLATINUM-BASED DOUBLETS AS FIRST-LINE THERAPY: ANALYSES FROM THE EUROPEAN FRAME OBSERVATIONAL STUDY

ABSTRACT Aim: Patients (pts) with brain metastases (mets) are often excluded from clinical trials and limited data exists. FRAME (2009-2012) was a prospective, non-interventional observational study of pts with advanced NSCLC receiving platinum (plt)-doublet chemotherapy as first-line treatment (FLT) across Europe. Thus, in FRAME unique real-life data could be collected on baseline characteristics, FLT and survival for NSCLC pts with brain mets. Methods: FLT decisions were at the discretion of the physicians under routine clinical practice. The primary objective of overall survival (OS) from FRAME was previously reported. Here, we describe baseline characteristics and survival for pts with brain mets at FLT initiation. Survival was estimated using Kaplan-Meier methods and unadjusted estimates are presented. Results: In FRAME overall, 1564 pts received plt in combination with: pemetrexed (pem; n = 569), gemcitabine (gem; n = 360), taxanes (tax; n = 295), vinorelbine (vin; n = 300), or other (n = 40); 263 (17%) of these pts had brain mets at FLT initiation. Pts with brain mets had a median age of 58 years [range: 33-84] (overall 64 years [range: 33-87], n = 1564), 64% were male (overall 72%), 84% had non-squamous histology (overall 72%), 21% had an ECOG performance status (PS) 2-3 (overall 17%), 58% received cisplatin as FLT plt backbone (overall 55%) and 34% received prior radiotherapy to the brain (overall 6%). Several baseline characteristics for pts with brain mets numerically varied among cohorts (Table 1, “other” cohort [n = 5] is not shown). For the overall study, median OS was 10.3 months (95% CI: 9.5-11.2). For pts with brain mets, median OS was 7.2 months (95% CI: 6.1-8.2); OS estimates for cohorts are shown in Table 1. Pts with brain mets FLT Baseline characteristics Pem n = 117 Gem n = 49 Tax n = 54 Vin n = 38 ≥70 yrs, % 12 25 20 21 ECOG PS 2-3, % 18 14 30 21 Never smoker, % 14 6 6 5 Non-squamous, % 97 69 70 82 Median OS, mos. (95% CI) 9.3 (6.2-11.9) 5.6 (4.1-8.4) 6.6 (3.7-7.8) 6.7 (5.2-9.3) Conclusions: Real-world data from the European FRAME study provide relevant information on NSCLC pts with brain mets, and may have implications on FLT management decisions for these pts. Disclosure: D. Moro-Sibilot: Consulting fees from Eli Lilly and Company, Roche, Astra Zeneca, Boehringer Ingelheim France, Amgen; J. De Castro Carpeno: Advisory board for Eli Lilly and Company, Roche and Pfizer; speakers bureau for Roche; K. Lesniewski-Kmak: Invited speaker for Eli Lilly and Company, Roche, Astra Zeneca, GSK, Amgen; J.G. Aerts: Research grant from and consultant for Eli Lilly and Company; advisory board for Eli Lilly and Company, Genentech, BMS; R. Villatoro: Speaker fee from Jansen, Pfizer; K. Kraaij: Employee and stockholder of Eli Lilly and Company; K. Nacerddine: Employee and stockholder of Eli Lilly and Company; Y. Dyachkova: Employee of Eli Lilly and Company; K. Smith: Employee and stockholder of Eli Lilly and Company; A. Girvan: Employee and stockholder of Eli Lilly and Company; C.M. Visseren-Grul: Employee and stockholder of Eli Lilly and Company; P.A. Schnabel: Research funding from Eli Lilly and Company. Speakers bureau for AstraZeneca, InterMune, Eli Lilly and Company, Novartis, Pfizer and Roche. Advisory board for Eli Lilly and Company, AstraZeneca, Novartis and Roche. All other authors have declared no conflicts of interest.

1247PANALYSIS OF PATIENTS TREATED WITH CISPLATIN OR CARBOPLATIN-BASED DOUBLET CHEMOTHERAPY IN THE EUROPEAN FRAME OBSERVATIONAL STUDY

ABSTRACT Aim: FRAME was a prospective observational study of patients (pts) receiving platinum (plt)-based chemotherapy as first-line treatment (FLT) for advanced or metastatic non-small cell lung cancer (NSCLC) across Europe between 2009 and 2012. Methods: The study primary objective of overall survival was previously reported. Here, we describe the association between baseline characteristics and the physicians choice of a cisplatin (cis) or carboplatin (cb) backbone for FLT observed in FRAME. The distribution of baseline characteristics was compared by t-test or k2-test and summarized by propensity of receiving cb estimated by logistic regression. Cohorts were matched by propensity score; survival for matched pts was compared using Kaplan-Meier approach. Results: In total, 1520 pts received either cis (n = 825) or cb (n = 695) in combination with either: pemetrexed, gemcitabine, taxanes or vinorelbine, and were analyzed here. Pts prescribed cb were on average older, had worse ECOG PS and were more likely to have squamous histology than pts who received cis (Table 1); they also had more pre-existing conditions (cardiovascular p Cis (n = 825) Cb (n = 695) p-value ≥70 yrs (%) 15 47 ECOG PS (%) Gr 0-1 Gr 2-3 87 12 77 22 FLT (+plt) (%) pemetrexed (n = 567) gemcitabine (n = 360) taxanes (n = 293) vinorelbine (n = 300) 47 23 9 21 26 24 31 19 Histology (%) Squamous (sq) Non-sq 23 75 26 70 .031 Conclusions: FRAME observed that age, ECOG PS, pre-existing conditions and pathological diagnosis have strong associations with the choice of cis or cb in FLT for advanced or metastatic NSCLC across Europe. Disclosure: D. Moro-Sibilot: Consulting fees from Eli Lilly and Company, Roche, Astra Zeneca, Boehringer Ingelheim France, Amgen; J. De Castro Carpeno: Speakers Bureau for Roche; Advisory board for Eli Lilly and Company, Roche and Pfizer; K. Kmak-Lesniewski: Invited speaker for Eli Lilly, Roche, Astra Zeneca, GSK, Amgen; J.G. Aerts: Research grant from and Consultant for Eli Lilly and Company. Advisory board for Eli Lilly and Company, Roche Genentech and BMS; R. Villatoro: Speaker fee from Jansen, Pfizer; K. Kraaij: Employee and stockholder of Eli Lilly and Company; K. Nacerddine: Employee and stockholder of Eli Lilly and Company; Y. Dyachkova: Employee and stockholder of Eli Lilly and Company; K. Smith: Employee of Eli Lilly and Company; A. Girvan: Employee and stockholder of Eli Lilly and Company; C.M. Visseren-Grul: Employee and stockholder of Eli Lilly and Company; P.A. Schnabel: Speakers Bureau for AstraZeneca, InterMune, Eli Lilly and Company, Novartis, Pfizer, Roche. Advisory board for AstraZeneca, Eli Lilly and Company, Novartis, Roche. Prior research funding from Eli Lilly and Company. All other authors have declared no conflicts of interest.

Cáncer de pulmón (II). Tratamiento médico

PUNTOS CLAVE Tratamiento quirurgico. Dentro del cancer de pulmon, la variante de celula no pequena supone el 80% de casos * La cirugia es el tratamiento de eleccion de los casos de cancer de pulmon no microcitico que son resecables. Tratamiento medico. El tratamiento medico del cancer de pulmon no microcitico puede conseguir un beneficio en la mayoria de los pacientes. Tratamiento adyuvante. La quimioterapia adyuvante, basada en un esquema de cisplatino incrementa la supervivencia conseguida con la cirugia. Tratamiento neoadyuvante. El tratamiento neoadyuvante puede rescatar enfermos en estadio IIIA para la cirugia. Extension locorregional. En situacion de afectacion locorregional (estadio IIIB), la combinacion de quimioterapia y radioterapia, a ser posible concomitante, es la opcion terapeutica de eleccion. Enfermedad avanzada. La quimioterapia ha demostrado un beneficio clinico frente al mejor tratamiento de soporte, tanto en supervivencia como en reduccion de los sintomas relacionados. Terapia biologica. Las nuevas terapias dirigidas, como cetuximab y hevacizumab, ofrecen resultados muy interesantes. En caso de cetuximab, un subgrupo de pacientes con un perfil muy concreto, ya que se trata predominantemente de mujeres, con la variante de adenocarcinoma bronquioloalveolar, no fumadoras. En lo que respecta a Avastin, los resultados de este anticuerpo contra el VEGF son muy prometedores, ya que ha aumentado la supervivencia en combinacion con quimioterapia. --------------------------------------------------------------------------------