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Accreditation/Credit Designation

Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians' Education Resource®, LLC designates this enduring material for a maximum of 2.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physicians' Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669, for 2.0 Contact Hours.

Acknowledgment of Commercial Support

This activity is supported by educational grants from AstraZeneca, Genomic Health, Inc., Illumina, Inc., Lilly, and Novartis Pharmaceuticals Corporation.

For further information concerning Lilly grant funding, visit www.lillygrantoffice.com.

Community Practice Connections™: 1st Annual International Congress of Oncology Pathology™: Towards Harmonization of Pathology and Oncology Standards

Release Date: August 30, 2017
Expiration Date: August 30, 2018
Media: Internet - based

 

Activity Overview

Community Practice Connections™: 1st Annual International Congress of Oncology Pathology (ICOP)™: Towards Harmonization of Pathology and Oncology Standards is a continuing medical education (CME)-certified activity based on a symposium of the same name held in New York, NY, on June 24, 2017.

ICOP was developed to bring together oncologists and pathologists to facilitate awareness of recent advancements in the field of cancer pathology and enhance multidisciplinary collaboration. The live portion of the activity provided a review of the latest information on key topics in cancer pathology that can readily be applied to clinical practice in a variety of settings. Leading experts addressed critical topics in pathology screening for malignancies commonly encountered in clinical practice. From a foundation of tumor-specific discussions, our clinical experts reviewed clinical guidelines, explored new concepts and clinical research, and addressed obstacles to optimizing practice.

This interactive, online CME activity is based on the presentations that took place during the ICOP meeting, and includes additional interviews with 3 of the distinguished ICOP faculty members, including both meeting chairs, exploring clinically relevant questions from the community clinician perspective. Important topics addressed in this activity include:

  • Recent advancements in clinical testing for commonly-encountered malignancies
  • Clinical considerations for genomic and targeted assays
  • Recent clinical trial data for commonly-encountered malignancies that may help to tailor patient treatment approaches
  • Molecular and cytogenetic testing applications
  • Advancements in the understanding of the immunogenicity of commonly-encountered malignancies
  • Strategies to optimize patient outcomes through multidisciplinary collaboration

Acknowledgment of Commercial Support

This activity is supported by educational grants from AstraZeneca, Genomic Health, Inc., Illumina, Inc., Lilly, and Novartis Pharmaceuticals Corporation.

For further information concerning Lilly grant funding, visit www.lillygrantoffice.com.

CME/CE Activity Table of Contents

  • Module 1. Tissue, Issues, and Looking Toward the Horizon
  • Module 2. Patient Selection for Immunotherapy: To PD-L1 and Beyond
  • Module 3. The ABCs of Lung Cancer Management

Instructions for This Activity and Receiving Credit

  • You will need to login to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “educational content/video files” will be available for your reference.
  • In order to receive a cme/ce certificate, participants must complete the activity.
  • Complete the posttest and pass with a score of 70% or higher, complete the evaluation and then click on request for credit. Participants may immediately download a cme/ce certificate upon completion of these steps.

Target Audience

This educational activity is directed toward pathologists and oncologists interested in the management of patients with cancer. Fellows, residents, nurse practitioners, nurses, physician assistants, researchers, and other health care professionals interested in the treatment of patients with cancer are also invited to participate.

Learning Objectives

At the conclusion of this activity, you should be better prepared to:

  • Describe recent advancements in the understanding of the pathogenesis and relevant biomarkers of commonly-encountered malignancies
  • Select evidence-based molecular and cytogenetic testing strategies for commonly-encountered malignancies
  • Compare the roles of genomic and targeted assays in patient management
  • Develop multidisciplinary strategies to optimize cancer diagnosis and management
  • Apply current clinical trial data in cancer pathology to the tailoring of patient treatment protocols

Faculty, Staff, and Planners' Disclosures

Chairs

Alain Borczuk, MD
Professor of Pathology and Laboratory Medicine
Vice Chairman for Anatomic Pathology
Department of Pathology and Laboratory Medicine
Weill Cornell Medicine
New York, NY

Disclosure: None.

Balazs Halmos, MD, MS
Professor of Clinical Medicine
Director, Thoracic Oncology
Director, Clinical Cancer Genomics
Albert Einstein College of Medicine/Montefiore Medical Center
Bronx, NY

Disclosure: Grant Research Support: Eli-Lilly, Novartis, Mirati, Ariad, Merck, Boehringer-Ingelheim, Astra-Zeneca,Pfizer, Genentech, Astra-Zeneca; Consultant: Pfizer, Genentech, Astra-Zeneca, Boehringer-Ingelheim, Foundation One

Faculty

Charles G. Drake, MD, PhD
Director Genitourinary Oncology
Co-Director Immunotherapy Program
Associate Director, Herbert Irving Comprehensive Cancer Center
Columbia University Medical Center, Division of Hematology /Oncology
New York, NY

Disclosure: Grant Research Support: Bristol-Myers Squibb, Janssen, Aduro Biotech; Conulstant: Agenus, Dendreon, NexImmune, ImmunExcite, Janssen, Lilly, Merck, Pierre Fabre, Roche/Genentech; Patents: AZ Medimmune, Bristol-Myers Squibb, Janssen.

The staff of PER® have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME/CE activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME/CE activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME/CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME/CE activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER®.




PER Pulse™ Recap (1 of 3)
Tissue, Issues, and Looking Toward the Horizon

There is great clinical interest in the role that key mutations play in the determination of treatment options for a variety of malignancies, including non–small cell lung cancer (NSCLC). Assessment of EGFR, ALK, and ROS1 mutations all may govern treatment decisions pertaining to patients with lung adenocarcinoma, and PD-L1 assessment also has a role in the treatment paradigm for patients with non-small cell carcinoma. Inter- and intratumor heterogeneity are both important when establishing diagnosis and assessing for the potential emergence of treatment resistance. Although tissue biopsy remains a key component of diagnostic assessment, liquid biopsy is an alternative option for molecular testing that is being assessed.1

When pursuing diagnostic evaluation of patients with suspected lung cancer, those patients who have several potential sites of metastases should have a biopsy of the primary tumor or mediastinal lymph nodes if it is too risky or technically challenging to biopsy a metastasis. Different DNA mutational analytic techniques have different degrees of sensitivity, with next-generation sequencing (NGS) approaches displaying greater sensitivity than Sanger sequencing methods.2

In the case of patients with advanced NSCLC, it is imperative to obtain data from testing in a timely fashion to help optimize treatment approaches.3 Although such data may not be immediately actionable for patients with earlier stages of NSCLC, they are becoming increasingly relevant for patients who may be candidates for study participation, or to help advise patients regarding long-term options. In this segment, Dr. Borczuk addresses key points regarding assessment of tumor pathology for patients with lung cancer and other commonly encountered malignancies.

References

  1. NCCN Guidelines Version 8.2017. Non-Small Cell Lung Cancer. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed August 16, 2017.
  2. Gao J, Wu H, Shi X, et al. Comparison of next-generation sequencing, quantitative PCR, and Sanger sequencing for mutation profiling of EGFR, KRAS, PIK3CA and BRAF in clinical lung tumors. Clin Lab. 2016;62(4):689-696.
  3. Lim C, Tsao MS, Le LW, et al. Biomarker testing and time to treatment decision in patients with advanced non-small-cell lung cancer. Ann Oncol. 2015;26(7):1415-1421. doi: 10.1093/annonc/mdv208.



PER Pulse™ Recap (2 of 3)
Tailoring Treatment Decisions for Genitourinary and Pulmonary Malignancies: To PD-L1 and Beyond

A great deal of progress has been made in the development of precision medicine for patients with a variety of genitourinary and pulmonary malignancies. Precision medicine has been used for risk stratification and guidance of treatment approaches that may ultimately lead to improvement in patient outcomes. As an example, prostate cancer risk stratification may be improved through the use of different tests that identify specific molecular markers.1 These techniques may help to determine who should be offered a more aggressive curative approach versus active surveillance.1

PD-L1 expression has been studied as a possible biomarker for PD-1 and PD-L1 directed therapies in several different tumor types. Although many cancers generate antigens that may be recognized by the immune system, adaptive immune resistance frequently develops through multiple mechanisms such as local immunosuppression, systemic disruption of T-cell signaling, and induction of tolerance.2 There are several ways for tumors to avoid being targeted through the use of immune checkpoints. PD-1 is an immune checkpoint receptor that is expressed by activated T cells, mediating immunosuppression. It is found primarily in peripheral tissues, where T cells may encounter tumor cells that express the immunosuppressive PD-L1 ligand. Disruption of the interaction between PD-1 and PD-L1 can promote antitumor activity.2

Studies have also shown that monoclonal antibodies against PD-1 and PD-L1 have durable treatment response in patients with NSCLC. However, there are factors that limit the utility of PD-L1 assessment. Levels of PD-L1 protein are heterogeneous within NSCLC tumors, with potential challenges of discordance between lesions, sampling errors within lesions, and tumor changes over time.3 There is also a great deal of variability among PD-L1 assays, with some measuring PD-L1 in tumor cells, while others measure tumor-infiltrating immune cells, and still others measure both.4 The assays also have different cutoff levels for positivity.5

Of note, tumor mutational burden has also shown promises a predictor of treatment response with immune checkpoint inhibitor therapy. Next generation predictive markers are also being developed. An RNA profiling data set from several different cancer types supported the concept that tumor infiltration with activated T cells is necessary for response to PD-1 checkpoint inhibitor therapies.6 T-cell inflamed gene expression signatures may be useful for identifying which patients may respond to anti–PD1 therapy.6 In this segment, Dr. Drake addresses PD-L1 assessment and other techniques to evaluate tumors to guide treatment decisions.

References

  1. Zhuang L, Johnson MT. How precisely can prostate cancer be managed? Int Neurourol J. 2016;20(Suppl 2):S120-130. doi: 10.5213/inj.1632724.362.
  2. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-2454. doi: 10.1056/NEJMoa1200690.
  3. McLaughlin J, Han G, Schalper KA, et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol. 2016;2(1):46-54. doi: 10.1001/jamaoncol.2015.3638.
  4. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515(7528):558-562. doi: 10.1038/nature13904.
  5. Apolo AB. PDL1: the illusion of an ideal biomarker. Eur Urol Focus. 2016;1(3):269-271. doi: 10.1016/j.euf.2015.04.005.
  6. Piha-Paul SA, Bennouna J, Albright A, et al. T-cell inflamed phenotype gene expression signatures to predict clinical benefit from pembrolizumab across multiple tumor types. J Clin Oncol. 2016;34(15_suppl):1536-1536. doi: 10.1200/JCO.2016.34.15_suppl.153



PER Pulse™ Recap (3 of 3)
The ABCs of Lung Cancer Management

Immunotherapy treatment options for patients with cancer continue to gain in prominence. There are a variety of different tumor microenvironments which vary by the presence of tumor-infiltrating lymphocytes and PD-L1 expression, and may have a role in treatment selection for patients with non¬–small cell lung cancer (NSCLC).1 For patients with nonsquamous NSCLC who have progressed during or after platinum-based chemotherapy whose tumors were PD-L1 positive, nivolumab has a median overall survival rate that was nearly twice that of patients treated with docetaxel.2 This stands in contrast to patients with squamous NSCLC, where PD-L1 expression is not associated with nivolumab activity. The KEYNOTE-001 study assessed the efficacy and safety of pembrolizumab in the treatment of patients with advanced NSCLC, and also sought to establish and validate a specific expression level of the PD-L1 ligand that might be associated with likelihood of clinical benefit.3 In patients treated with pembrolizumab who had expression of PD-L1 with at least 50% of tumor cells, the overall survival with pembrolizumab than with docetaxel.3

Mechanisms of resistance to targeted therapy also need to be understood to help optimize patient outcomes. Although gefitinib and erlotinib are often effective treatments for EGFR-mutant lung cancer, resistance often emerges. MET amplification may promote resistance to gefitinib.4 The EGFR T790M mutation is the most common mechanism associated with resistance to first- or second-generation tyrosine kinase inhibitors in NSCLC.5 Resistance to ALK inhibitors used in the treatment of patients with NSCLC also occurs, with different ALK inhibitors being associated with a different spectrum of ALK resistance mutations.6 Phenomena such as this emphasize the importance of obtaining repeat biopsies and genotypic characterization after disease progression on targeted therapies.6 Resistance to immunotherapy may also occur, and molecular evidence pertaining to resistance mechanisms is emerging.7

There are advantages and disadvantages to different biopsy techniques for patients with NSCLC. Tissue-based testing may not reflect tumor heterogeneity, which has led investigators to assess the potential of circulating tumor DNA-based testing.8 These liquid biopsies allow for the assessment of cell-free ctDNA and/or circulating tumor cells, although the platforms that are currently available focus primarily on ctDNA.8 CtDNA-based testing is dependent on tumor burden/shedding. Although polymerase chain reaction (PCR) based platforms which include allele-specific PCR may have a short turnaround time, they usually address a small number of common mutations, such as EGFR, KRAS, BRAF, and ALK.8 In this segment, Dr. Halmos discusses key pathologic features of NSCLC that may help to guide treatment, as well as strategies to optimize the collaboration between pathologists and oncologists.

References

  1. Teng MW, Ngiow SF, Ribas A, Smyth MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res. 2015;75(11):2139-2145. doi: 10.1158/0008-5472.CAN-15-0255.
  2. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627-1639.
  3. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018-2028. doi: 10.1056/NEJMoa1501824.
  4. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB2 signaling. Science. 2007;316(5827):1039-1043. doi: 10.1056/NEJMoa1507643.
  5. Sun JM, Lee SH, Ahn JS, et al. Osimertinib for the treatment of non-small cell lung cancer. Expert Opin Pharmacother. 2017;18(2):225-231. doi: 10.1080/14656566.2017.1285283.
  6. Gainor JF, Dardaei L, Yoda S, et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov. 2016;6(10):1118-1133.
  7. Koyama S, Akbay EA, Li YY, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7:10501.
  8. Vendrell JA, Mau-Them FT, Béganton B, et al. Circulating cell free tumor DNA detection as a routine tool for lung cancer patient management. Int J Mol Sci. 2017;18(2). pii: E264. doi: 10.3390/ijms18020264.







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