Search

I Moya-Horno,1 J Cortés1,2 1Department of Medical Oncology, Instituto Oncológico Baselga, Hospital Quirón, 2Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Barcelona, Spain Abstract: Breast cancer tumors that demonstrate gene amplification or overexpression of human epidermal growth factor receptor 2 (HER2) are classified as HER2-positive. They account for approximately 15% of all breast cancers and represent an adverse prognostic factor. Over the past years, many new therapies have become available for the treatment of breast cancer. Particularly, the treatment of patients with HER2-positive breast cancer has developed with the arrival of anti-HER2 targeted therapies that have been proven to increase survival in both the metastatic and early-stage settings of the disease. Trastuzumab, a monoclonal antibody targeting HER2, significantly improves survival in HER2-positive breast cancer. Nevertheless, it is still a challenge to evolve anti-HER2 therapies, as the disease may progress. Pertuzumab inhibits HER2 by binding to a different HER2 epitope than trastuzumab and represents a complementary mechanism of action to trastuzumab. The efficacy and safety of pertuzumab in combination with trastuzumab with or without chemotherapy have been demonstrated in both advanced and early stages of HER2-positive breast cancer. Herein, we review the available data on the use of pertuzumab for the treatment of patients with HER2-positive breast cancer. Keywords: pertuzumab, anti-HER2 targeted therapies, HER2-positive breast cancer

ALK, ROS1, and RET fusions and MET∆ex14 variant associate with response to targeted therapies in non-small-cell lung cancer (NSCLC). Technologies for fusion testing in tissue must be adapted to liquid biopsies, which are often the only material available. In this study, circulating-free RNA (cfRNA) and extracellular vesicle RNA (EV-RNA) were purified from liquid biopsies. Fusion and MET∆ex14 transcripts were analyzed by nCounter (Nanostring) and digital PCR (dPCR) using the QuantStudio ® System (Applied Biosystems). We found that nCounter detected ALK, ROS1, RET, or MET∆ex14 aberrant transcripts in 28/40 cfRNA samples from positive patients and 0/16 of control individuals (70% sensitivity). Regarding dPCR, aberrant transcripts were detected in the cfRNA of 25/40 positive patients. Concordance between the two techniques was 58%. Inferior results were obtained when analyzing EV-RNA, where nCounter often failed due to a low amount of input RNA. Finally, results of dPCR testing in serial liquid biopsies of five patients correlated with response to targeted therapy. We conclude that nCounter can be used for multiplex detection of fusion and MET∆ex14 transcripts in liquid biopsies, showing a performance comparable with next-generation sequencing platforms. dPCR could be employed for disease follow-up in patients with a known alteration. cfRNA should be preferred over EV-RNA for these analyses., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non-small-cell lung cancer and melanoma patients. Cell-free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA-Q-PCR or next-generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty-three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatment decisions, such as initiation of osimertinib treatment or selection of specific ALK tyrosine-kinase inhibitors. In conclusion, fluids close to metastatic sites are superior to blood for the detection of relevant mutations and can offer valuable clinical information, particularly in patients progressing to targeted therapies., (© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Introduction: Despite all treatment advances, lung cancer is still the main cause of death worldwide. Treatment for resectable stage IIIA remains controversial including definitive chemoradiotherapy and induction treatment followed by surgery. After definitive chemoradiation up to 35% of patients will relapse locally. Experience with salvage resection after definitive chemoradiotherapy in lung cancer is limited. We present our experience in 27 patients who underwent surgical resection after definitive treatment., Patients and Methods: Between January 2007 and December 2016, 27 patients were evaluated in our department for surgical resection after receiving definitive chemoradiation treatment in different institutions. We conducted a retrospective study gathering the following data: age, gender, clinical and pathologic stage, histology, chemotherapy treatment regimen, radiotherapy dosage, surgical procedure and complications. Time between surgical resection and last follow-up was used to calculate Overall Survival (OS). Disease-Free Survival (DFS) was calculated from surgical resection to diagnosis of relapse., Results: Most of the patients were men with a median age of 56.09 years. Median follow-up time was 46.94 months. All patients received platinum-based chemotherapy regimen and high-dose radiotherapy, except for one patient who received 45 Gy. Lobectomy and bilobectomy was performed in 7 patients each, and pneumonectomy in 13. Complications appeared in 5 patients. Bronchopleural fistula appeared in two patients, and only one death in the early postoperative period. The analysis showed an OS of 75.56 months, with 1-year, 3-year and 5-year survival of 74.1%, 57.8% and 53.3% respectively., Conclusion: Salvage surgery in selected patients is technically feasible, with low morbidity and mortality rates and good long-term outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: In a significant percentage of advanced non-small cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses at time to progression. We prospectively analyzed the appearance of genetic alterations associated with resistance in liquid biopsies of advanced NSCLC patients progressing to targeted therapies using the NGS platform., Methods: A total of 24 NSCLC patients were included in the study, 22 progressing to tyrosine kinase inhibitors and two to other treatments. Liquid biopsies samples were obtained and analyzed using the GeneRead TM QIAact Lung DNA UMI Panel, designed to enrich specific target regions and containing 550 variant positions in 19 selected genes frequently altered in lung cancer tumors. Previously, a retrospective validation of the panel was performed in clinical samples., Results: Of the 21 patients progressing to tyrosine kinase inhibitors with valid results in liquid biopsy, NGS analysis identified a potential mechanism of resistance in 12 (57%). The most common were acquired mutations in ALK and EGFR , which appeared in 8/21 patients (38%), followed by amplifications in 5/21 patients (24%), and KRAS mutations in one patient (5%). Loss of the p.T790M was also identified in two patients progressing to osimertinib. Three of the 21 (14%) patients presented two or more concomitant alterations associated with resistance. Finally, an EGFR amplification was found in the only patient progressing to immunotherapy included in the study., Conclusions: NGS analysis in liquid biopsies of patients progressing to targeted therapies using the GeneReader platform is feasible and can help the oncologist to make treatment decisions., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2018.10.12). The series “Targeted Therapy and Non-Small Cell Lung Cancer: A New Era?” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Treatment for advanced non-small cell lung cancer (NSCLC) has been significantly improved in recent years with the incorporation of drugs targeting antiangiogenesis and more specifically genomic alterations such as the EGFR mutations and ALK translocations. However, most patients invariably progress and die. The emergence of immune checkpoint inhibitors targeting the pathways involved in tumor-induced immunosuppression have redefined the management of the disease, achieving significant long-lasting responses with manageable safety profiles, regardless of histology. Still, response rates with immunotherapy are deemed suboptimal. Current efforts are focusing on new potential combination strategies with synergistic antitumor activity, using immune checkpoint blockade as a partner for targeted agents. Herein we discuss the available data on the combined use of immunotherapy, including PD-1/PD-L1 and CTLA-4 inhibitors, with EGFR and ALK inhibitors and comment on the current status of immunotherapy plus antiangiogenic drugs for molecularly unselected advanced NSCLC., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Haemolytic uraemic syndrome (HUS) is a rare thromboembolic complication observed in patients with cancer. It is characterised by the clinical triad of acute renal failure, microangiopathic haemolytic anaemia and thrombocytopaenia. It may be associated with a variety of aetiologies, including chemotherapeutic agents such as mitomycin, cisplatin, bleomycin, 5-fluorouracil and, most recently, gemcitabine. We report a 70-year-old patient treated with gemcitabine who developed haemolytic uraemic syndrome.