Gonzalo Recondo

Novel approaches to target HER2-positive breast cancer: trastuzumab emtansine

The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast carcinomas. Prior to the development of targeted therapies, HER2-positive breast cancer was associated with more aggressive disease and poor prognosis. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that results from the combination of trastuzumab and DM1, a derivative of the antimicrotubule agent maytansine. This molecule has the ability to enhance cytotoxic drug delivery to specifically targeted cells that overexpress HER2, therefore, maximizing efficacy while sparing toxicity. In recent years, T-DM1 has shown to improve outcomes in metastatic HER2-positive breast cancer that is resistant to trastuzumab. In addition, T-DM1 is currently being tested in the neoadjuvant and adjuvant settings to identify patients who may benefit from this therapy. This review focuses on the mechanism of action, early and late-phase clinical trials, and ongoing studies of T-DM1 in HER2-positive breast cancer.

Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice

BRCA1/2 mutations in Latin America are scarcely documented and in serious need of knowledge about the spectrum of BRCA pathogenic variants, information which may alter clinical practice and subsequently improve patient outcome. In addition, the search for data on testing policies in different regions constitutes a fundamental strength for the present study, which analyzes BRCA1/2 gene sequences and large rearrangements in 940 probands with familial and/or personal history of breast/ovary cancer (BOC). In non-mutated DNA samples, Multiplex Ligation-dependent Probe Amplification assays (MLPA) were used for the analysis of large rearrangements. Our studies detected 179 deleterious mutations out of 940 (19.04%) probands, including 5 large rearrangements and 22 novel mutations. The recurrent mutations accounted for 15.08% of the total and only 2.87% of the probands analyzed, very different from a Hispanic panel previously described. In conclusion: a) this first comprehensive description of the spectrum in BRCA1/2 sheds light on the low frequency of recurrent mutations; b) this information is key in clinical practice to select adequate sequencing studies in our population, subsequently improve patient outcome and prevent damage associated to false normal reports resulting from the use of invalid population panels; c) panels of mutations from other populations should be cautiously validated before imported, even those of apparently similar origin, a concept to be considered beyond significance in Argentina.

Immunotherapy for Non-Small Cell Lung Cancer - Finally a Hint of Hope.

Lung cancer is a major public health problem worldwide and the leading cause of cancerrelated mortality in developed countries. Significant advances have been made especially with the discovery of targeted agents. However, only a small proportion of patients carry activating mutations; until recently conventional chemotherapy and angiogenesis inhibitors were the preferred treatment for the vast majority of patients. Now, the successful experience of anti-PD-1 agents may have opened the door to a novel and previously unexplored dimension in the treatment of lung cancer: immunotherapy. In this mini-review we will discuss the current applications and future consequences related this topic, paying special attention to the clinical studies that constitute the scientific evidence to supports its use.

What is the Current Role of Immunotherapy for Colon Cancer

Colon cancer is a leading cause of cancer related mortality. Until very recently the only existing options that medical oncologists had to treat metastatic colon cancer were a combination of chemotherapy, anti-EGFR and anti-angiogenic agents. We currently have the first proof that immune therapies could be an effective approach to battle colorectal cancers that carry a mismatch repair machinery deficient phenotype. It is expected that as our knowledge of the different mechanisms of immune-resistance grows, this therapeutic modality might soon be applicable to all patients. However, due to the continuous increase in the cost of oncological drugs, some treatment overheads may soon become prohibitive for many. In this review we will examine the current evidence related to this topic with the objective to provide the reader with concise but practical information about the potential role of immunotherapy in CRC.

P20 Molecular Characterization of Non–Small Cell Lung Cancer (NSCLC) Patients by Next Generation Sequencing: Preliminary Data

and its value as a prognostic biomarker in patients with metastatic nonesmall cell lung cancer (NSCLC). Method: The clinical chart of consecutive metastatic NSCLC patients treated in Edgardo Rebagliati Martins National Hospital, Lima-Perú, between July 2014 and December 2015, were retrospectively evaluated. Epidemiological, disease and extension data were collected, as well as white cell differential before either, definitive treatment or best supportive care. Survival analysis was performed using log-rank test, Kaplan-Meier method and Cox regression analysis using NLR cut-off point of 5 as previously reported. R language was used for statistical analysis. Results: Ninety clinical charts of advanced NSCLC patients were evaluated, of which 36 cases were considered for final analysis. The mean age was 69 years (SD 11.9). Twenty-three patients were female (63.9%), 28 were nonsmokers (77.8%) and 32 had adenocarcinoma (88.9%), median NLR was 3.4. The median overall survival (OS) was 7.95 months. Median OS for patients with NLR 3 5 was 3.97 months vs. 12.07 months for NLR < 5 (p 1⁄4 0.0041). Cox analysis for NLR < 5 was performed, adjusting with variables such as age (HR: 0.27, p 1⁄4 0.008), gender (HR: 0.30, p 1⁄4 0.012) and systemic treatment (HR: 0.34, p 1⁄4 0.038). Finally, we performed multivariate analysis adjusting for all variables that potentially can influence in mortality such as age, gender, systemic treatment and metastatic sites and we found HR 0.27 for NLR < 5 (95%CI 0.09 0.84, p 1⁄4 0.024). Conclusion: NLR < 5 was statistically associated with better overall survival. Multivariate analysis adjusted by age, gender, systemic treatment and metastatic compromise, was able to predict better overall survival, with a hazard ratio of 0.27 for NLR < 5. The retrospective design and limitations of our study only allow us to generate the hypothesis that NLR < 5 could be an easy and inexpensive marker of better survival in metastatic lung cancer patients and support design of larger and prospective trials.

P49 Lung Adenocarcinoma with Double Heterozygote EGFR mutation and Combined Resistance: ALK Translocation and EGFR T790M

P49 Lung Adenocarcinoma with Double Heterozygote EGFR mutation and Combined Resistance: ALK Translocation and EGFR T790M V. Denninghoff, V. Wainsztein, M.T. Cuello, G. Recondo, E. Rojas Bilbao, A. Avagnina, G. Recondo Molecular Biology, CEMIC, Buenos Aires/AR, Clinical Oncology, CEMIC, CABA/AR, CEMIC, CABA/AR, Oncology, CEMIC, Buenos Aires/AR, Instituto de Oncologia Angel H Roffo, CABA/AR, Pathology, CEMIC, Buenos Aires/AR