EVITA - A double-blind, vehicle controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity Ann. Oncol. (IF 11.855) Pub Date : 2018-01-18 R-D Hofheinz, S Lorenzen, J Trojan, J Ocvirk, T J Ettrich, S-E Al-Batran, H Schulz, N Homann, H-P Feustel, M Schatz, M Kripp, N Schulte, M Tetyusheva, S Heeger, S Vlassak, K Merx
Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab.
Joint Adolescent - Adult Early Phase Clinical Trials to Improve Access to New Drugs for Adolescents with Cancer Proposals from the Multi-stakeholder Platform - ACCELERATE Ann. Oncol. (IF 11.855) Pub Date : 2018-01-16 N Gaspar, L V Marshall, D Binner, R Herold, R Rousseau, P Blanc, R Capdeville, J Carleer, C Copland, Y Kerloeguen, K Norga, L Pacaud, M-A Sevaux, C Spadoni, J Sterba, F Ligas, T Taube, M Uttenreuther-Fischer, S Chioato, M A O'Connell, B Geoerger, J-Y Blay, J C Soria, S Kaye, B Wulff, L Brugières, G Vassal, A D J Pearson
The impressive progress recently observed in adult cancers through the introduction of new drugs has not yet been translated to adolescents between 12 and 17 years of age. Currently adolescents are grouped with children, so their access to new, effective drugs already available for adults is delayed because paediatric drug development starts late relative to adult programmes. Moreover, specific early phase trials designed exclusively for adolescents in rare diseases recruit poorly, even if conducted internationally. Evidence has shown that adolescents demonstrate similar toxicity profiles, maximum tolerated doses and pharmacokinetic parameters to adults. Although they may have specific vulnerabilities and their interests should be protected, they are, in many countries in Europe, entitled to provide informed consent themselves. There are no insurmountable scientific, medical, or regulatory barriers to their participation in Phase-I to III adult trials. Based on a review of the literature, the multi-stakeholder platform ACCELERATE, with representatives from academia, patient/parent advocacy groups, regulatory agencies and pharmaceutical companies, proposes the inclusion of adolescents in adult Phase-I to III trials of cancer drugs targeting a relevant disease or mechanism of action, without requiring preceding specific paediatric trials. The trials, however, should be delivered in age-appropriate clinical care settings by clinicians with adolescent trial expertise. Joint adolescent-adult trials will not exclude adolescents from participating in paediatric trials, as these approaches are complementary. This strategy is considered to be safe, rational, efficient and would provide more clinical trial options and accelerate drug development for adolescents with cancer.
A mutational signature associated with alcohol consumption and prognostically significantly mutated driver genes in esophageal squamous cell carcinoma Ann. Oncol. (IF 11.855) Pub Date : 2018-01-16 X C Li, M Y Wang, M Yang, H J Dai, B F Zhang, W Wang, X L Chu, X Wang, H Zheng, R F Niu, W Zhang, K X Chen
Esophageal squamous cell carcinoma (ESCC) is often diagnosed at an advanced and incurable stage. Information on driver genes and prognosticators in ESCC remains incomplete. The objective was to elucidate significantly mutated genes (SMGs), mutational signatures, and prognosticators in ESCC.
Multicenter French harmonization study for PD-L1 IHC testing in non-small cell lung cancer Ann. Oncol. (IF 11.855) Pub Date : 2018-01-16 J Adam, N Le Stang, I Rouquette, A Cazes, C Badoual, H Pinot-Roussel, L Tixier, C Danel, F Damiola, D Damotte, F Penault-Llorca, S Lantuéjoul
Various PD-L1 immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDT).
Unique Genetic Profiles from Cerebrospinal Fluid Cell-free DNA in Leptomeningeal Metastases of EGFR-mutant Non-Small Cell Lung Cancer: A New Medium of Liquid Biopsy Ann. Oncol. (IF 11.855) Pub Date : 2018-01-15 Y S Li, B Y Jiang, J J Yang, X C Zhang, Z Zhang, J Y Ye, W Z Zhong, H Y Tu, H J Chen, Z Wang, C R Xu, B C Wang, H J Du, S Chuai, H Han-Zhang, J Su, Q Zhou, X N Yang, W B Guo, H H Yan, Y H Liu, L X Yan, B Huang, M M Zheng, Y L Wu
Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Activity and safety of afatinib in a window pre-operative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN) Ann. Oncol. (IF 11.855) Pub Date : 2018-01-15 J P Machiels, P Bossi, J Menis, M Lia, C Fortpied, Y Liu, R Lhommel, M Lemort, S Schmitz, S Canevari, L De Cecco, M Guzzo, R Bianchi, P Quattrone, F Crippa, T Duprez, Y Lalami, M Quiriny, N de Saint Aubain, P M Clement, R Coropciuc, E Hauben, L F Licitra
To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN).
Final Results of a Multi-institutional Phase II Trial of Re-Irradiation with Concurrent Weekly Cisplatin and Cetuximab for Recurrent or Second Primary Squamous Cell Carcinoma of the Head and Neck Ann. Oncol. (IF 11.855) Pub Date : 2018-01-15 M J Awan, L Nedzi, D Wang, V Tumati, B Sumer, X-J Xie, I Smith, J Truelson, R Hughes, L L Myers, P Lavertu, S Wong, M Yao
The optimal regimen of chemotherapy and re-irradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multi-center Phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC.
Clinical Considerations of the Role of Palbociclib in the Management of Advanced Breast Cancer Patients With and Without Visceral Metastases Ann. Oncol. (IF 11.855) Pub Date : 2018-01-11 N C Turner, R S Finn, M Martin, S-A Im, A DeMichele, J Ettl, V Diéras, S Moulder, O Lipatov, M Colleoni, M Cristofanilli, D R Lu, A Mori, C Giorgetti, S Iyer, C Huang Bartlett, K A Gelmon
This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor−positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases.
Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board Ann. Oncol. (IF 11.855) Pub Date : 2018-01-09 S P Somashekhar, M -J Sepúlveda, S Puglielli, A D Norden, E H Shortliffe, C Rohit Kumar, A Rauthan, N Arun Kumar, P Patil, K Rhee, Y Ramya
Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer.
Amplicon-based next-generation sequencing of plasma cell-free DNA for detection of driver and resistance mutations in advanced non-small cell lung cancer Ann. Oncol. (IF 11.855) Pub Date : 2018-01-09 N Guibert, Y Hu, N Feeney, Y Kuang, V Plagnol, G Jones, K Howarth, J F Beeler, C P Paweletz, G R Oxnard
Genomic analysis of plasma cell-free DNA is transforming lung cancer care, however available assays are limited by cost, turnaround time, and imperfect accuracy. Here we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC).
Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO. Ann. Oncol. (IF 11.855) Pub Date : 2018-01-08 E Dell'Aquila, C Cremolini, T Zeppola, S Lonardi, F Bergamo, G Masi, M Stellato, F Marmorino, M Schirripa, F Urbano, M Ronzoni, G Tomasello, A Zaniboni, P Racca, A Buonadonna, G Allegrini, E Fea, S Di Donato, S Chiara, G Tonini, D Tomcikova, L Boni, A Falcone, D Santini
Neutrophil/Lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial.
APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution Ann. Oncol. (IF 11.855) Pub Date : 2018-01-08 S Venkatesan, R Rosenthal, N Kanu, N McGranahan, J Bartek, S A Quezada, J Hare, R S Harris, C Swanton
The APOBEC mutational signature has only recently been detected in a multitude of cancers through next-generation sequencing. In contrast, APOBEC has been a focus of virology research for over a decade. Many lessons learnt regarding APOBEC within virology are likely to be applicable to cancer. In this review, we explore the parallels between the role of APOBEC enzymes in HIV and cancer evolution. We discuss data supporting the role of APOBEC mutagenesis in creating HIV genome heterogeneity, drug resistance, and immune escape variants. We hypothesize similar functions of APOBEC will also hold true in cancer.
Cancer immunotherapy full speed ahead Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 I Melero, B Navarro, A Teijeira, G Coukos
The field of immunotherapy is celebrating with well-justified pride on the recent regulatory approvals of PD-1/PD-L1 blocking agents for a number of new malignant tumor indications, as well as of the adoptive transfer of CAR-T cells gene-targeted to CD19, which are amazingly efficacious for the treatment of children with refractory acute lymphoid leukemia as well as adult patients with relapsed or refractory large B-cell lymphoma. Patients with advanced metastatic tumors of many kinds are not only responding but also achieve long-lasting remission. Such clinical efficacy results are certainly unprecedented in oncology but, even if dazzled, we must move on. In the January issue of Annals of Oncology, Shalabi et al. provide an analysis of the magnitude of the global immunotherapy effort with a comprehensive survey of public data estimating the number of clinical trials, agents and the investment volumes. This is to be taken only as an indication of the prominence and priority of the cancer immunotherapy field in both academia and industry .
Novel tools to assist neoepitope targeting in personalized cancer immunotherapy Ann. Oncol. (IF 11.855) Pub Date : 2017-10-30 S K Saini, N Rekers, S R Hadrup
Current cancer immunotherapy approaches utilize the remarkable surveillance capacity of the human immune system, which is capable of recognizing and eliminating cancer cells based on identification of tumor-associated antigens arising as a consequence of the transformation process. Among these, mutational-derived neoepitopes have proved to be powerful targets for tumor elimination and mutational load has been shown to correlate with the clinical response to treatment with checkpoint inhibitors in many different tumor types. This suggests a crucial role for neoepitope recognition in T-cell-mediated tumor eradication. Consequently, strategies to further boost neoepitope recognition, through vaccination or adoptive cell transfer, has received substantial interest. Although such strategies have enormous potential, there are also considerable challenges associated with these approaches. In the present review, we will focus on how novel technological developments can facilitate and improve feasibility and efficacy in neoepitope targeting.
Preclinical and clinical development of neoantigen vaccines Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 L Li, S P Goedegebuure, W E Gillanders
Cancer neoantigens are antigens that result from somatic mutations present in individual cancers. Neoantigens are considered important targets for cancer immunotherapy because of their immunogenicity and lack of expression in normal tissues. Next-generation sequencing technologies and computational analysis have recently made neoantigen discovery possible. Although neoantigens are important targets of checkpoint blockade therapy, neoantigen vaccines are currently being investigated in preclinical models and early-phase human clinical trials. Preliminary results from these clinical trials demonstrate that dendritic cell, synthetic long peptide, and RNA-based neoantigen vaccines are safe, and capable of inducing both CD8+ and CD4+ neoantigen-specific T-cell responses. We and others are testing neoantigen vaccines in melanoma, breast cancer, non-small-cell lung cancer and other cancer types. Since cancers have evolved mechanisms to escape immune control, it is particularly important to study the efficacy of neoantigen vaccines in combination with other immunotherapies including checkpoint blockade therapy, and immune therapies targeting the immunosuppressive tumor microenvironment.
Mechanisms regulating T-cell infiltration and activity in solid tumors Ann. Oncol. (IF 11.855) Pub Date : 2017-09-21 E Lanitis, D Dangaj, M Irving, G Coukos
T-lymphocytes play a critical role in cancer immunity as evidenced by their presence in resected tumor samples derived from long-surviving patients, and impressive clinical responses to various immunotherapies that reinvigorate them. Indeed, tumors can upregulate a wide array of defense mechanisms, both direct and indirect, to suppress the ability of Tcells to reach the tumor bed and mount curative responses upon infiltration. In addition, patient and tumor genetics, previous antigenic experience, and the microbiome, are all important factors in shaping the T-cell repertoire and sensitivity to immunotherapy. Here, we review the mechanisms that regulate T-cell homing, infiltration, and activity within the solid tumor bed. Finally, we summarize different immunotherapies and combinatorial treatment strategies that enable the immune system to overcome barriers for enhanced tumor control and improved patient outcome.
Intratumoral immunotherapy: using the tumor as the remedy Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 A Marabelle, L Tselikas, T de Baere, R Houot
Immune checkpoint-targeted monoclonal antibodies directed at Programmed Death Receptor 1 (PD-1), Programmed Death Ligand 1 (PD-L1) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4) are currently revolutionizing the prognosis of many cancers. By blocking co-inhibitory receptors expressed by antitumor T cells, these antibodies can break the immune tolerance against tumor cells and allow the generation of durable cancer immunity. Benefits in overall survival over conventional therapies have been demonstrated for patients treated with these immunotherapies, leading to multiple approvals of such therapies by regulatory authorities. However, only a minority of patients develop an objective tumor response with long-term survival benefits. Moreover, the systemic delivery of immunotherapies can be responsible for severe auto-immune toxicities. This risk increases dramatically with anti-PD(L)1 and anti-CTLA-4 combinations and currently hampers the development of triple combination immunotherapies. In addition, the price of these novel treatments is probably too high to be reimbursed by health insurances for all the potential indications where immunotherapy has shown activity (i.e. in more than 30 different cancer types). Intratumoral immunotherapy is a therapeutic strategy which aims to use the tumor as its own vaccine. Upon direct injections into the tumor, a high concentration of immunostimulatory products can be achieved in situ, while using small amounts of drugs. Local delivery of immunotherapies allows multiple combination therapies, while preventing significant systemic exposure and off-target toxicities. Despite being uncertain of the dominant epitopes of a given cancer, one can therefore trigger an immune response against the relevant neo-antigens or tumor-associated antigens without the need for their characterization. Such immune stimulation can induce a strong priming of the cancer immunity locally while generating systemic (abscopal) tumor responses, thanks to the circulation of properly activated antitumor immune cells. While addressing many of the current limitations of cancer immunotherapy development, intratumoral immunotherapy also offers a unique opportunity to better understand the dynamics of cancer immunity by allowing sequential and multifocal biopsies at every tumor injection.
Antigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapy Ann. Oncol. (IF 11.855) Pub Date : 2017-09-01 A R Sánchez-Paulete, A Teijeira, F J Cueto, S Garasa, J L Pérez-Gracia, A Sánchez-Arráez, D Sancho, I Melero
Dendritic cells (DCs) are the main professional antigen-presenting cells for induction of T-cell adaptive responses. Cancer cells express tumor antigens, including neoantigens generated by nonsynonymous mutations, but are poor for antigen presentation and for providing costimulatory signals for T-cell priming. Mounting evidence suggests that antigen transfer to DCs and their surrogate presentation on major histocompatibility complex class I and II molecules together with costimulatory signals is paramount for induction of viral and cancer immunity. Of the great diversity of DCs, BATF3/IRF8-dependent conventional DCs type 1 (cDC1) excel at cross-presentation of tumor cell-associated antigens. Location of cDC1s in the tumor correlates with improved infiltration by CD8+ T cells and tumor-specific T-cell immunity. Indeed, cDC1s are crucial for antitumor efficacy using checkpoint inhibitors and anti-CD137 agonist monoclonal antibodies in mouse models. Enhancement and exploitation of T-cell cross-priming by cDC1s offer opportunities for improved cancer immunotherapy, including in vivo targeting of tumor antigens to internalizing receptors on cDC1s and strategies to increase their numbers, activation and priming capacity within tumors and tumor-draining lymph nodes.
Informatics for cancer immunotherapy Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 J Hammerbacher, A Snyder
The rapid development of immunomodulatory cancer therapies has led to a concurrent increase in the application of informatics techniques to the analysis of tumors, the tumor microenvironment, and measures of systemic immunity. In this review, the use of tumors to gather genetic and expression data will first be explored. Next, techniques to assess tumor immunity are reviewed, including HLA status, predicted neoantigens, immune microenvironment deconvolution, and T-cell receptor sequencing. Attempts to integrate these data are in early stages of development and are discussed in this review. Finally, we review the application of these informatics strategies to therapy development, with a focus on vaccines, adoptive cell transfer, and checkpoint blockade therapies.
Antigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapy Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 A R Sánchez-Paulete, A Teijeira, F J Cueto, S Garasa, J L Pérez-Gracia, A Sánchez-Arráez, D Sancho, I Melero
Ann Oncol 2017; (doi: 10.1093/annonc/mdx237)
Targeting the fibroblast growth factor receptor 2 in gastric cancer: promise or pitfall? Ann. Oncol. (IF 11.855) Pub Date : 2018-01-02 C Hierro, M Alsina, M Sánchez, V Serra, J Rodon, J Tabernero
Ann Oncol 2017; 28: 1207–1216 (doi: 10.1093/annonc/mdx081)
A phase II study of temsirolimus added to low-dose weekly carboplatin and paclitaxel for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) Ann. Oncol. (IF 11.855) Pub Date : 2018-01-02 L A Dunn, M G Fury, H Xiao, S S Baxi, E J Sherman, S Korte, C Pfister, S Haque, N Katabi, A L Ho, D G Pfister
Ann Oncol 2017; 28: 2533–2538 (doi: 10.1093/annonc/mdx346)
Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab Ann. Oncol. (IF 11.855) Pub Date : 2018-01-02 S M Swain, A Schneeweiss, L Gianni, J J Gao, A Stein, M Waldron-Lynch, S Heeson, M S Beattie, B Yoo, J Cortes, J Baselga
Ann Oncol 2017; 28: 761–768 (doi: 10.1093/annonc/mdw695)
Body mass index and 20-specific cancers: re-analyses of dose-response meta-analyses of observational studies. Ann. Oncol. (IF 11.855) Pub Date : 2017-12-28 E K Choi, H B Park, K H Lee, J H Park, M Eisenhut, H J van der Vliet, G Kim, J I Shin
Objectives were to provide an overview and understand the strength of evidence and extent of potential biases and validity of claimed associations between Body Mass Index (BMI) and risk of developing cancer.
Prognostic markers for colorectal cancer; estimating ploidy and stroma Ann. Oncol. (IF 11.855) Pub Date : 2017-12-27 H E Danielsen, T S Hveem, E Domingo, M Pradhan, A Kleppe, R A Syvertsen, I Kostolomov, J A Nesheim, H A Askautrud, A Nesbakken, R A Lothe, A Svindland, N Shepherd, M Novelli, E Johnstone, I Tomlinson, R Kerr, D J Kerr
We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage CRC.
S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase 3, non-inferiority trial Ann. Oncol. (IF 11.855) Pub Date : 2017-12-27 Y Yamada, T Denda, M Gamoh, I Iwanaga, S Yuki, H Shimodaira, M Nakamura, T Yamaguchi, H Ohori, K Kobayashi, M Tsuda, Y Kobayashi, Y Miyamoto, M Kotake, K Shimada, A Sato, S Morita, S Takahashi, Y Komatsu, C Ishioka
Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment for metastatic colorectal cancer (mCRC). We performed a randomized, open-label, phase 3 trial to determine whether S-1 and irinotecan plus bevacizumab is non-inferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS).
Aromatase Inhibitors and the Risk of Colorectal Cancer in Post-Menopausal Women with Breast Cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-12-27 F Khosrow-Khavar, H Yin, A Barkun, N Bouganim, L Azoulay
A large trial of post-menopausal women with breast cancer reported an imbalance in colorectal cancer events with aromatase inhibitors (AIs), compared with tamoxifen in the adjuvant setting. This unexpected signal was observed within 3 years of randomization. To date, no observational studies have examined this important safety question in the natural setting of clinical practice. Thus, the objective of this study was to determine whether AIs, when compared with tamoxifen, are associated with increased risk of colorectal cancer in post-menopausal women with breast cancer.
CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two Phase II trials Ann. Oncol. (IF 11.855) Pub Date : 2017-12-23 G Goss, C-M Tsai, F A Shepherd, M-J Ahn, L Bazhenova, L Crinò, F de Marinis, E Felip, A Morabito, R Hodge, M Cantarini, M Johnson, T Mitsudomi, P A Jänne, J C-H Yang
Central nervous system (CNS) metastases are common in patients with non-small-cell lung cancer (NSCLC). Osimertinib has shown systemic efficacy in patients with CNS metastases and early clinical evidence shows efficacy in the CNS. To evaluate osimertinib activity further, we present a pre-specified subgroup analysis of CNS response using pooled data from two Phase II studies: AURA extension (NCT01802632) and AURA2 (NCT02094261).
Impact of homologous recombination deficiency biomarkers on outcomes in patients with triple-negative breast cancer treated with doxorubicin-based adjuvant chemotherapy (SWOG S9313) Ann. Oncol. (IF 11.855) Pub Date : 2017-12-23 P Sharma, W E Barlow, A K Godwin, H Pathak, K Isakova, D Williams, K M Timms, A R Hartman, R J Wenstrup, H M Linden, D Tripathy, G N Hortobagyi, D F Hayes
Homologous recombination deficiency (HRD) causing alterations have been reported in triple-negative breast cancer (TNBC). We hypothesized that TNBCs with HRD alterations might be more sensitive to anthracycline plus cyclophosphamide-based chemotherapy and report on HRD status and BRCA1 promoter methylation (PM) as prognostic markers in TNBC patients treated with adjuvant doxorubicin (A) and cyclophosphamide (C) in SWOG9313.
Radiotherapy and anti-PD-1/PD-L1 combinations in lung cancer: building better translational research platforms Ann. Oncol. (IF 11.855) Pub Date : 2017-12-22 T Kordbacheh, J Honeychurch, F Blackhall, C Faivre-Finn, T Illidge
Despite the unheralded success of immune checkpoint blockade in delivering durable responses for some patients with non-small cell lung cancer (NSCLC), the majority of patients do not respond. PD-L1 tumour expression and pre-existing tumour T-cell infiltration have been correlated with improved clinical outcomes to anti-PD-1/anti-PD-L1. However, patients with tumours that are negative for PD-L1 expression can also respond to treatment. Strategies to combine other treatment modalities like radiotherapy with immune checkpoint inhibitors are being investigated as means of improving the response rates to PD-1/PD-L1 antibody blockade. Radiotherapy induces immunogenic changes in cancer cells, can adaptively upregulate tumour cell PD-L1 expression and can improve the efficacy of anti-PD-1/anti-PD-L1 therapy. How we design future clinical trials in NSCLC also depends on practical considerations of delivering these treatment combinations, such as radiotherapy dose, fractionation and field volume, as well as scheduling with immune checkpoint blockade. Here, we review reasons for resistance to anti-PD-1/anti-PD-L1 and how radiotherapy may be utilised in combination with these drugs to enhance their effect by building better translational research platforms.
Autologous Stem Cell Transplantation After Second Line Brentuximab Vedotin in Relapsed or Refractory Hodgkin Lymphoma Ann. Oncol. (IF 11.855) Pub Date : 2017-12-20 A F Herrera, J Palmer, P Martin, S Armenian, N-C Tsai, N Kennedy, F Sahebi, T Cao, L E Budde, M Mei, T Siddiqi, L Popplewell, S Rosen, L Kwak, A Nademanee, S Forman, R Chen
Background: We previously demonstrated that brentuximab vedotin (BV) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation (AHCT). Here we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography (PET) adapted dose-escalation of second-line BV was utilized. Patients and Methods: Patients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for 2 cycles. Patients in complete remission (CR) after 2 cycles received 2 additional cycles of BV at 1.8 mg/kg, while patients with stable disease or partial response were escalated to 2.4 mg/kg for 2 cycles. All patients, regardless of treatment cohort, proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV.
Androgen Deprivation Therapy and Risk of Rheumatoid Arthritis in Patients with Localized Prostate Cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-12-18 D D Yang, A Krasnova, K T Nead, T K Choueiri, J C Hu, K E Hoffman, J B Yu, D E Spratt, F Y Feng, Q -D Trinh, P L Nguyen
Androgens are generally immunosuppressive, and men with untreated hypogonadism are at increased risk for autoimmune conditions. To date, there has been no evidence linking androgen deprivation therapy (ADT) to autoimmune diseases, including rheumatoid arthritis (RA). We investigated the association between ADT and RA in patients with prostate cancer.
Interim monitoring for non-inferiority trials: minimizing patient exposure to inferior therapies Ann. Oncol. (IF 11.855) Pub Date : 2017-12-18 E L Korn, B Freidlin
The goal of a non-inferiority randomized trial is to demonstrate that an experimental treatment is not unacceptably worse than a standard treatment. The experimental treatment is known to have less toxicity or other quality-of-life benefits as compared to the standard treatment, so that a small decrement in efficacy would be acceptable. Interim monitoring of randomized trials is used to stop trials early if the conclusions of the trial become definitive early. In the context of a non-inferiority trial, of special interest is stopping a trial early when the experimental treatment is inferior to the standard treatment.
A polymorphic MYC response element in KBTBD11 influences colorectal cancer risk, especially in interaction with a MYC regulated SNP rs6983267 Ann. Oncol. (IF 11.855) Pub Date : 2017-12-18 J Gong, J Tian, J Lou, X Wang, J Ke, J Li, Y Yang, Y Gong, Y Zhu, D Zou, X Peng, N Yang, S Mei, R Zhong, J Chang, X Miao
MYC is a well-established cancer driver gene regulating the expression of numerous genes, indicating that polymorphisms in MYC response elements could affect tumorigenesis through altering MYC regulation. We performed integrative multistage study to evaluate the effects of variants in MYC response elements and colorectal cancer (CRC) risk.
Phase I-II clinical trial design: A state-of-the-art paradigm for dose finding Ann. Oncol. (IF 11.855) Pub Date : 2017-12-18 F Yan, P F Thall, K H Lu, M R Gilbert, Y Yuan
Conventional phase I algorithms for finding a phase-2 recommended dose (P2RD) based on toxicity alone is problematic because the maximum tolerated dose (MTD) is not necessarily the optimal dose with the most desirable risk-benefit trade-off. Moreover, the increasingly common practice of treating an expansion cohort at a chosen MTD has undesirable consequences that may not be obvious.
Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters - patient centered endpoints in trials of maintenance therapy Ann. Oncol. (IF 11.855) Pub Date : 2017-12-18 M Friedlander, J Rau, C K Lee, W Meier, A Lesoin, J-W Kim, A Poveda, M Buck, G Scambia, M Shimada, F Hilpert, M T King, P Debruyne, A Bolog, S Malander, B J Monk, E Petru, P Calvert, T J Herzog, C Barrett, A du Bois
Health related quality of life (HRQOL) was a secondary endpoint in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient centered endpoints.
The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 P N Aguiar, L A Perry, J Penny-Dimri, H Babiker, H Tadokoro, R A de Mello, G L Lopes
Ann Oncol 2017; 00: 1–8 (doi:10.1093/annonc/mdx305)
Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 T E Witzig, K Tobinai, L Rigacci, T Ikeda, A Vanazzi, M Hino, Y Shi, J Mayer, L. J Costa, C D Bermudez Silva, J Zhu, D Belada, K Bouabdallah, J G Kattan, J Kuruvilla, W S Kim, J-F Larouche, M Ogura, M Ozcan, L Fayad, C Wu, J Fan, A-L Louveau, M Voi, F Cavalli
Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus.
Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 S M Swain, M S Ewer, G Viale, S Delaloge, J-M Ferrero, M Verrill, R Colomer, C Vieira, T L Werner, H Douthwaite, D Bradley, M Waldron-Lynch, A Kiermaier, J Eng-Wong, C Dang
Anti-HER2 therapies are associated with a risk of increased cardiac toxicity, particularly when part of anthracycline-containing regimens. We report cardiac safety of pertuzumab, trastuzumab, and chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer.
Circulating cell-free DNA as predictor of treatment failure after neo-adjuvant chemo-radiotherapy before surgery in patients with locally advanced rectal cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 J V Schou, F O Larsen, B S Sørensen, R Abrantes, A K Boysen, J S Johansen, B V Jensen, D L Nielsen, KL Spindler
Treatment of patients with locally advanced rectal cancer (LARC) is based on a combination of chemo-radiotherapy (CRT) and surgery. The rate of distant recurrences remains over 25%. Circulating cell-free DNA (cfDNA) in plasma is a mixture of normal and cancer-specific DNA segments, and is a promising biomarker in patients with colorectal cancer. The aim of our study was to investigate plasma cfDNA as a prognostic marker for outcome in patients with LARC treated with neoadjuvant CRT and surgery.
Role of up-front autologous stem cell transplantation in peripheral T-cell lymphoma for patients in response after induction: An analysis of patients from LYSA centers Ann. Oncol. (IF 11.855) Pub Date : 2017-12-15 G Fossard, F Broussais, I Coelho, S Bailly, E Nicolas-Virelizier, E Toussaint, C Lancesseur, F Le Bras, E Willems, E Tchernonog, T Chalopin, R Delarue, R Gressin, A Chauchet, E Gyan, G Cartron, C Bonnet, C Haioun, G Damaj, P Gaulard, L Fornecker, H Ghesquières, O Tournilhac, M Gomes da Silva, R Bouabdallah, G Salles, E Bachy
Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem cell transplant (ASCT) is, therefore, still intensely debated.
European Society for Medical Oncology (ESMO) position paper on supportive and palliative care Ann. Oncol. (IF 11.855) Pub Date : 2017-12-14 K Jordan, M Aapro, S Kaasa, C I Ripamonti, F Scotté, F Strasser, A Young, E Bruera, J Herrstedt, D Keefe, B Laird, D Walsh, J Y Douillard, A Cervantes
Oncology has come a long way in addressing patients’ quality of life, together with developing surgical, radio-oncological and medical anticancer therapies. However, the multiple and varying needs of patients are still not being met adequately as part of routine cancer care. Supportive and palliative care interventions should be integrated, dynamic, personalised and based on best evidence. They should start at the time of diagnosis and continue through to end-of-life or survivorship. ESMO is committed to excellence in all aspects of oncological care during the continuum of the cancer experience. Following the 2003 ESMO stand on supportive and palliative care (Cherny N, Catane R, Kosmidis P. ESMO takes a stand on supportive and palliative care. Ann Oncol 2003; 14(9): 1335–1337), this position paper highlights the evolving and growing gap between the needs of cancer patients and the actual provision of care. The concept of patient-centred cancer care is presented along with key requisites and areas for further work.
Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-12-13 F Janku, L K Johnson, D D Karp, J T Atkins, P A Singleton, J Moss
Ann Oncol 2016; 27: 2032–2038 (doi:10.1093/annonc/mdw317)
Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium Ann. Oncol. (IF 11.855) Pub Date : 2017-12-13 J M Ordóñez-Me, V Walter, B Schöttker, M Jenab, M G O’Doherty, F Kee, B Bueno-de-Mesquita, P H M Peeters, B H Stricker, R Ruiter, A Hofman, S Söderberg, P Jousilahti, K Kuulasmaa, N D Freedman, T Wilsgaard, A Wolk, L M Nilsson, A Tjønneland, J R Quirós, F J B van Duijnhoven, P D Siersema, P Boffetta, A Trichopoulou, H Brenner
Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited.
Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post-hoc analysis of COU-AA-301 and COU-AA-302 Ann. Oncol. (IF 11.855) Pub Date : 2017-12-11 D Cella, S Traina, T Li, K Johnson, K F Ho, A Molina, N D Shore
Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aimed to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC).
A randomized trial of induction docetaxel-cisplatin-5FU followed by concomitant cisplatin-RT versus concomitant cisplatin-RT in nasopharyngeal carcinoma (GORTEC 2006-02) Ann. Oncol. (IF 11.855) Pub Date : 2017-12-11 M Frikha, A Auperin, Y Tao, F Elloumi, N Toumi, P Blanchard, P Lang, S Sun, S Racadot, J Thariat, M Alfonsi, C Tuchais, A Cornely, A Moussa, J Guigay, J Daoud, J Bourhis
concomitant CT-RT is a standard of care in locally advanced nasopharyngeal carcinoma (NPC) and a role for induction CT is not established.
Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer. Ann. Oncol. (IF 11.855) Pub Date : 2017-12-11 R Condorelli, L Spring, J O’Shaughnessy, L Lacroix, C Bailleux, V Scott, J Dubois, RJ Nagy, RB Lanman, AJ Iafrate, F Andre, A Bardia
While deregulation of the cyclin D1-CDK4/6-retinoblastoma pathway is common in hormone receptor positive (HR+) breast cancer, Rb is usually intact in HR+ breast cancer, and targeted CDK 4/6 inhibitors that act upstream of Rb, are routinely being utilized in clinical practice. However, factors that can lead to clinical resistance to CDK 4/6 inhibitors are not known.
Neuroblastoma PTPome analysis unveils association of DUSP5 and PTPN1 expression with poor prognosis Ann. Oncol. (IF 11.855) Pub Date : 2017-12-08
Ann Oncol 2017; 28 (Suppl 7): mdx511.023 (abstr. 57). https://doi.org/10.1093/annonc/mdx511.023.
A randomized phase II study evaluating different maintenance schedules of nab-Paclitaxel in the first-line treatment of metastatic breast cancer: final results of the IBCSG 42-12/BIG 2-12 SNAP trial Ann. Oncol. (IF 11.855) Pub Date : 2017-12-08 A Gennari, Z Sun, U Hasler-Strub, M Colleoni, M J Kennedy, R Von Moos, J Cortés, M J Vidal, B Hennessy, J Walshe, K Amillano Parraga, K Ribi, J Bernhard, S Murillo Morales, O Pagani, A Barbeaux, S Borstnar, M Rabaglio-Poretti, R Maibach, M M Regan, G Jerusalem
The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses.
Analysis of Angiogenesis Biomarkers for Ramucirumab Efficacy in Patients with Metastatic Colorectal Cancer from RAISE, a Global, Randomized, Double-Blind, Phase III Study Ann. Oncol. (IF 11.855) Pub Date : 2017-12-07 J Tabernero, R R Hozak, T Yoshino, A L Cohn, R Obermannova, G Bodoky, R Garcia-Carbonero, T-E Ciuleanu, D C Portnoy, J Prausová, K Muro, R W Siegel, R J Konrad, H Ouyang, S A Melemed, D Ferry, F Nasroulah, E Van Cutsem
The phase III RAISE trial (NCT01183780) demonstrated that the vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 binding monoclonal antibody ramucirumab plus 5-fluororuracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo+FOLFIRI as second-line metastatic colorectal cancer (mCRC) treatment. To identify patients who benefit the most from VEGFR-2 blockade, the RAISE trial design included a prospective and comprehensive biomarker program that assessed the association of biomarkers with ramucirumab efficacy outcomes.
LAG-3: another brake to release in breast cancer? Ann. Oncol. (IF 11.855) Pub Date : 2017-10-30 M Kok
Upregulation of inhibitory immune checkpoints is critical for the control of T-cell activation in order to prevent autoimmunity and tissue damage. It is now clear that tumors can hijack immune checkpoint mechanisms as protection against the anticancer T-cell response. Blockade of the PD-1/PD-L1 immune checkpoint pathway has created a revolution in the treatment of melanoma, lung cancer and several other cancer types. In metastatic breast cancer patients, the response rates to PD-1 blocking antibodies are modest (4%–25%), but durable responses are seen [1–7]. Given that the majority of patients do not have clinical benefit, there is an urgent need to improve immunotherapy for breast cancer patients. This optimization is not a paved road and requires the integration of different parallel approaches, such...
Role of adjuvant chemotherapy in early-stage endometrioid and clear-cell ovarian cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-09-18 D Lorusso, S Pignata
With more than 200 000 new cases annually worldwide , ovarian cancer represents the sixth most common cancer among women and the most lethal gynecologic malignancy.
Incremental improvement in osteosarcoma chemotherapy? Ann. Oncol. (IF 11.855) Pub Date : 2017-10-30 S M Schuetze
Osteosarcoma is one of the first solid cancers for which a survival benefit from adjuvant chemotherapy was established [1, 2]. After decades of clinical research to improve on results obtained in the 1980s, the long-standing chemotherapy regimen of doxorubicin and cisplatin with or without methotrexate remains a standard treatment of osteosarcoma, resulting in a 5-year survival rate of more than 60% in patients with localized disease [3, 4]. In patients with metastatic osteosarcoma at diagnosis, or with distant disease relapse after treatment of localized disease, the long-term survival rate is <20%, and new therapies are much needed for this group of patients . Neither the intensification of chemotherapy by adding ifosfamide and etoposide nor the use...
DPYD genotype-guided fluoropyrimidines dose: is it ready for prime time? Ann. Oncol. (IF 11.855) Pub Date : 2017-10-05 D Páez, R Salazar, J Tabernero
For over 50 years, fluoropyrimidines have been the cornerstone of anticancer drugs for various types of solid cancers. Treatment with these drugs—5-fluorouracil (FU) and its oral prodrugs, capecitabine and tegafur—is generally well-tolerated, except in a small proportion of patients who develop severe and life-threatening early toxicity. This toxicity is mainly associated with a deficiency of the primary fluoropyrimidine detoxifying enzyme, dihydropryrimidine dehydrogenase (DPD) . The drug labels of FU and capecitabine state DPD deficiency as a contraindication, but they give no warning for the 3%–8% of the population who are partially DPD deficient.
DPYD genotype-guided dose individualization to improve patient safety of fluoropyrimidine therapy: call for a drug label update Ann. Oncol. (IF 11.855) Pub Date : 2017-08-02 L M Henricks, F L Opdam, J H Beijnen, A Cats, J H M Schellens
The fluoropyrimidine anticancer drugs, especially 5-fluorouracil (5-FU) and capecitabine, are frequently prescribed for several types of cancer, including breast, colorectal, head and neck and gastric cancer. In the current drug labels of 5-FU and capecitabine in the European Union and the United States, no adaptive dosing strategies are incorporated for polymorphic metabolism of 5-FU. Although treatment with fluoropyrimidines is generally well tolerated, a major clinical limitation is that a proportion of the treated population experiences severe, sometimes life-threatening, fluoropyrimidine-related toxicity. This toxicity is strongly affected by interindividual variability in activity of dihydropyrimidine dehydrogenase (DPD), the main metabolic enzyme for inactivation of fluoropyrimidines, with an estimated 3%–8% of the population being partially DPD deficient. A reduced functional or abrogated DPD enzyme is often caused by genetic polymorphisms in DPYD, the gene encoding for DPD, and heterozygous carriers of such DPYD polymorphisms have a partial DPD deficiency. When these partially DPD deficient patients are treated with a full dose of fluoropyrimidines, they are generally exposed to toxic levels of 5-FU and its metabolites, and the risk of developing severe treatment-related toxicity is therefore significantly increased.
Emerging treatment paradigms for brain metastasis in non-small-cell lung cancer: an overview of the current landscape and challenges ahead Ann. Oncol. (IF 11.855) Pub Date : 2017-10-17 D Ulahannan, J Khalifa, C Faivre-Finn, S -M Lee
Advances in the last decade in genomic profiling and the identification of druggable targets amenable to biological agents have transformed the management and survival of a subgroup of patients with brain metastasis in non-small-cell lung cancer. In parallel, clinicians have reevaluated the role of whole brain radiotherapy in selected patients with brain metastases to reduce neurocognitive toxicity. Continual progress in this understudied field is required: optimization of the sequence of schedules for therapies in patients with brain metastases of differing genomic profiles, focusing on new strategies to overcome mechanisms of biological resistance and increasing drug penetrability into the central nervous system. This review summarizes the field to date and possible treatment strategies based on current evidence.
Meta-analysis of individual patient safety data from six randomized, placebo-controlled trials with the antiangiogenic VEGFR2-binding monoclonal antibody ramucirumab Ann. Oncol. (IF 11.855) Pub Date : 2017-09-10 D Arnold, C S Fuchs, J Tabernero, A Ohtsu, A X Zhu, E B Garon, J R Mackey, L Paz-Ares, A D Baron, T Okusaka, T Yoshino, H H Yoon, M Das, D Ferry, Y Zhang, Y Lin, P Binder, A Sashegyi, I Chau
Ramucirumab, the human immunoglobulin G1 monoclonal antibody receptor antagonist of vascular endothelial growth factor receptor 2, has been approved for treating gastric/gastroesophageal junction, non-small-cell lung, and metastatic colorectal cancers. With the completion of six global, randomized, double-blind, placebo-controlled, phase III trials across multiple tumor types, an opportunity now exists to further establish the safety parameters of ramucirumab across a large patient population.
Incorporating BEAMing technology as a liquid biopsy into clinical practice for the management of colorectal cancer patients: an expert taskforce review Ann. Oncol. (IF 11.855) Pub Date : 2017-09-04 J García-Foncillas, E Alba, E Aranda, E Díaz-Rubio, R López-López, J Tabernero, A Vivancos
The importance of mutation identification for advanced colorectal cancer treatment with anti-epidermal growth factor receptor agents is well established. However, due to delays in turnaround time, low-quality tissue samples, and/or lack of standardization of testing methods a significant proportion of patients are being treated without the information that Kirsten rat sarcoma and neuroblastoma rat sarcoma (RAS) testing can provide. The detection of mutated circulating tumor DNA by BEAMing technology addresses this gap in care and allows these patients to receive international guideline-recommended expanded RAS testing with rapid turnaround times. Furthermore, the overall concordance between OncoBEAM RAS colorectal cancer testing and standard of care tissue testing is very high (93.3%). This article presents an overview of the clinical utility and potential applications of this minimally invasive method, such as early detection of emergent resistance to anti-epidermal growth factor receptor therapy. If appropriately implemented, BEAMing technology holds considerable promise to enhance the quality of patient care and improve clinical outcomes.
Immunotherapy in pancreatic ductal adenocarcinoma: an emerging entity? Ann. Oncol. (IF 11.855) Pub Date : 2017-09-04 I H Sahin, G Askan, Z I Hu, E M O’Reilly
The genomic-plasticity of the immune system creates a broad immune repertoire engaged to tackle cancer cells. Promising clinical activity has been observed with several immune therapy strategies in solid tumors including melanoma, lung, kidney, and bladder cancers, albeit as yet immunotherapy-based treatment approaches in pancreatic ductal adenocarcinoma (PDAC) remain to have proven value. While translational and early clinical studies have demonstrated activation of antitumor immunity, most recent late-phase clinical trials have not confirmed the early promise in PDAC except in MSI-High PDAC patients. These results may in part be explained by multiple factors, including the poorly immunogenic nature of PDAC along with immune privilege, the complex tumor microenvironment, and the genetic plasticity of PDAC cells. These challenges have led to disappointments in the field, nonetheless they have also advanced our understanding that may tailor the future steps for immunotherapy for PDAC. Therefore, there is significant hope that progress is on the horizon.
Combined irradiation and targeted therapy or immune checkpoint blockade in brain metastases: toxicities and efficacy Ann. Oncol. (IF 11.855) Pub Date : 2017-08-02 A V Tallet, F Dhermain, E Le Rhun, G Noël, Y M Kirova
Targeted therapies (TT) and immune checkpoint inhibitors (ICI) are currently modifying the landscape of metastatic cancer management and are increasingly used over the course of many cancers treatment. They allow long-term survival with controlled extra-cerebral disease, contributing to the increasing incidence of brain metastases (BMs). Radiation therapy remains the cornerstone of BMs treatment (either whole brain irradiation or stereotactic radiosurgery), and investigating the safety profile of radiation therapy combined with TT or ICI is of high interest. Discontinuing an efficient systemic therapy, when BMs irradiation is considered, might allow systemic disease progression and, on the other hand, the mechanisms of action of these two therapeutic modalities might lead to unexpected toxicities and/or greater efficacy, when combined.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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