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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.

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Boehringer Ingelheim Pharmaceuticals, Inc.

Community Practice Connections™: Oncogenic Tumor Board in Advanced NSCLC: Leveraging Actionable Mutations Along the Disease Continuum to Optimize Patient Outcomes

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

 

Activity Overview

Community Practice Connections™: Oncogenic Tumor Board in Advanced NSCLC: Leveraging Actionable Mutations Along the Disease Continuum to Optimize Patient Outcomes is a continuing medical education (CME)-certified activity based on a symposium of the same name held in Chicago, Illinois, on June 4, 2017.

The management of advanced forms of lung cancer has been transformed in recent years because of remarkable developments in molecular diagnostics and new therapies. The targeting of known oncogenic drivers has allowed for the development of strategies that aim to improve efficacy and minimize toxicity compared with previous standards of care. Indeed, personalized care is now the standard of care in non–small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) have brought hope to patients with several types of cancer in multiple lines of therapy, including epidermal growth factor receptor (EGFR)-mutated and anaplastic lymphoma kinase (ALK)-translocated NSCLC. In patient populations that have received targeted treatments, impressive clinical benefit has been achieved with TKIs that target mutated EGFR or ALK. These changes are welcome, and the field continues to move forward, with new diagnostic techniques and an ever-expanding array of therapeutic options in the different lines of therapy. The continual advances in the treatment of patients with oncogenic driver–mutated NSCLC create practice and educational gaps for clinical oncologists who strive to maintain state-of-the-art care for their patients. To meet this educational need, this interactive live symposium has assembled internationally recognized experts in lung cancer research and care to provide cutting-edge approaches that can be applied immediately to clinical practice.

This CME activity consists of a series of brief interviews with 3 internationally recognized experts in lung cancer research and care exploring clinically relevant questions concerning the use of oncogenic-driven treatment from the community physician perspective. We invite you to join these experts as they guide participants through the rapidly evolving treatment landscape. Important topics addressed in this activity include:

  • The landscape of actionable oncogenic drivers in lung cancer in 2017
  • Choosing therapy for patients with EGFR-mutated NSCLC
  • Assessing and responding to acquired resistance
  • Therapeutic options for patients with ALK- and ROS1-rearranged lung cancer

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Boehringer Ingelheim Pharmaceuticals, Inc.

CME/CE Activity Table of Contents

  • Module 1: A Patient With EGFR-Mutated NSCLC
  • Module 2: A Patient With ALK-Rearranged NSCLC

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 medical oncologists who treat patients with lung cancer. Nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other healthcare professionals interested in the treatment of cancer may also participate.

Learning Objectives

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

  • Apply clinical trial evidence for decision making to personalize care in the frontline setting of NSCLC with actionable mutations
  • Outline multidisciplinary methods to facilitate tumor tissue characterization, rebiopsy, or liquid biopsies to identify actionable mutations in multiple lines of care for patients with lung cancer
  • Assess current and emerging strategies to address the problem of acquired resistance and relapse in patients with NSCLC
  • Personalize care via the use of tumor- and patient-specific characteristics for patients with advanced forms of NSCLC beyond disease progression

Faculty, Staff, and Planners' Disclosures

Chair

David R. Gandara, MD
Professor of Medicine
Division of Hematology/Oncology
Director, Thoracic Oncology Program
Senior Advisor to the Director
UC Davis Comprehensive Cancer Center
Sacramento, CA

Disclosure: Grant/Research Support: Genentech, Novartis, AstraZeneca; Consultant: Genentech, Novartis, AstraZeneca.

Faculty

Fred R. Hirsch, MD, PhD
Professor of Medicine and Pathology
Division of Medical Oncology
University of Colorado Denver School of Medicine
Associate Director for International Programs
University of Colorado Cancer Center
Aurora, CO

Disclosure: Grant Research Support: Bayer, Bristol-Myers Squibb; Consultant: Lilly, Genentech/Roche, Bristol-Myers Squibb, AstraZeneca.

Geoffrey R. Oxnard, MD
Assistant Professor of Medicine
Dana-Farber Cancer Institute
Harvard Medical School
Boston, MA
 

Disclosure: Conulstant: Ariad, AstraZeneca, Inivota, Novartis, Chugai Pharma, Bio-Rad Laboratories, Sysmex.

Heather A. Wakelee, MD
Associate Professor of Medicine (Oncology)
Stanford University Medical Center
Stanford, CA
 
 

Disclosure: Grant Research Support: Clovis Oncology, Exelixis, AstraZeneca/MedImmune, Genentech/Roche, Bristol-Myers Squibb, Gilead, Novartis, Xcovery, Pfizer, Celgene, Pharmacyclics, Lilly; Consultant: Peregrine, ACEA Biosciences, Pfizer, Helsinn Therapeutics, Genentech (uncompensated).

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)

The live continuing medical education activity, Oncogenic Tumor Board in Advanced NSCLC: Leveraging Actionable Mutations Along the Disease Continuum to Optimize Patient Outcomes, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing the therapeutic landscape exploiting oncogenic drivers in non–small cell lung cancer (NSCLC): David R. Gandara, MD; Fred R. Hirsch, MD, PhD; Geoffrey R. Oxnard, MD; and Heather A. Wakelee, MD. This program featured 3 engaging, case-based lectures followed by a multidisciplinary tumor board discussion of each case. This first of 3 PER Pulse™ Recaps reviews the key drivers for choosing first-line therapy for patients with EGFR-mutated NSCLC.

Below are some highlights from Dr. Wakelee’s lecture:

  • In patients with EGFR-mutated NSCLC, multiple study results demonstrate that EGFR tyrosine kinase inhibitors (TKIs) produce superior progression-free survival (PFS) compared with standard chemotherapy.
    • However, no overall survival (OS) benefit of EGFR TKIs has been confirmed in a randomized controlled trial.
    • The combined retrospective analysis of the LUX-Lung 3 and 6 trials shows an OS benefit with afatinib compared with chemotherapy, but only in the exon 19 deletion subset, suggesting that the exon 19 deletion makes tumors more sensitive to afatinib than does L858R or other mutations.
  • In LUX-Lung 7, a randomized phase II trial of first-line afatinib versus gefitinib, afatinib had a significant improvement in both overall response rate and PFS but not in OS, suggesting that afatinib may have an efficacy advantage over gefitinib, although no firm conclusions can be drawn from randomized phase II trials.
    • LUX-Lung 7 also demonstrated that these 2 TKIs had differences in their safety profiles, with more diarrhea, rash, and dose modifications in the afatinib arm and more transaminitis in the gefitinib arm.
  • The phase III ARCHER 1050 trial compared dacomitinib and gefitinib in first-line NSCLC. Dr Wakelee could not discuss the results of this trial at the meeting because they were still embargoed prior to presentation at the American Society of Clinical Oncology annual meeting. However, it has now been reported that dacomitinib produced a 5.5-month advantage in PFS and a 6.5-month advantage in duration of response compared with gefitinib.

For additional commentary about this topic and the Oncogenic Tumor Board in Advanced NSCLC: Leveraging Actionable Mutations Along the Disease Continuum to Optimize Patient Outcomes symposium, please visit www.gotoper.com.




PER Pulse™ Recap (2 of 3)

The live continuing medical education activity, Oncogenic Tumor Board in Advanced NSCLC: Leveraging Actionable Mutations Along the Disease Continuum to Optimize Patient Outcomes, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing the therapeutic landscape exploiting oncogenic drivers in non–small cell lung cancer (NSCLC): David R. Gandara, MD; Fred R. Hirsch, MD, PhD; Geoffrey R. Oxnard, MD; and Heather A. Wakelee, MD. This program featured 3 engaging, case-based lectures followed by a multidisciplinary tumor board discussion of each case. This second of 3 PER Pulse™ Recaps discusses the data in the recurrent disease setting for patients with EGFR mutations.

Below are some highlights from Dr Oxnard’s lecture:

  • Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) that has activity against EGFR T790M-positive NSCLC. In the phase III AURA3 trial, osimertinib demonstrated a 5.7-month improvement in progression-free survival (PFS) compared with a platinum/pemetrexed doublet in patients with EGFR T790M-positive disease.
    • Moreover, in this trial, patients with brain metastases had a PFS hazard ratio that was similar to the overall population (HR, 0.32 vs 0.30), indicating that osimertinib has promising activity in the central nervous system.
  • Results from the ASPIRATION trial show that patients with radiographic progression on erlotinib who were continued on erlotinib received an additional 3 months of benefit before erlotinib discontinuation, suggesting that postprogression EGFR TKI continuation may be a reasonable way to delay salvage therapy in some patients
  • The utility of plasma biopsies was studied using plasma and tissue samples from patients in the AURA trial of osimertinib.
    • Plasma biopsy had a sensitivity in detecting T790M mutations of 70% and a specificity of 69%, although the specificity of the EGFR driver mutations (exon 19 deletions and L858R) had a specificity >95%.
    • Based on these results, Dr. Oxnard reported using plasma biopsy as a quick screen for T790M mutation. If results are positive, he acts on the results; if they are negative, he does a reflex tumor biopsy and testing.
  • Many combination therapies are under investigation with EGFR TKIs. Because osimertinib has a favorable safety profile, it is an attractive partner, currently in clinical trials with at least 10 targeted agents. Notably, however, one of these combinations—osimertinib + durvalumab—has unacceptable toxicity, producing pneumonitis in 30% of patients.
  • The placebo-controlled IMPRESS trial of standard chemotherapy ± gefitinib in patients who progressed on first-line gefitinib demonstrated a lack of benefit with gefitinib continuation. Both arms had approximately 30% responses and more than a 5-month median PFS.

For additional commentary about this topic and the Oncogenic Tumor Board in Advanced NSCLC: Leveraging Actionable Mutations Along the Disease Continuum to Optimize Patient Outcomes symposium, please visit www.gotoper.com.




PER Pulse™ Recap (3 of 3)

The live continuing medical education activity, Oncogenic Tumor Board in Advanced NSCLC: Leveraging Actionable Mutations Along the Disease Continuum to Optimize Patient Outcomes, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing the therapeutic landscape exploiting oncogenic drivers in non–small cell lung cancer (NSCLC): David R. Gandara, MD; Fred R. Hirsch, MD, PhD; Geoffrey R. Oxnard, MD; and Heather A. Wakelee, MD. This program featured 3 engaging, case-based lectures followed by a multidisciplinary tumor board discussion of each case. This third of 3 PER Pulse™ Recaps describes management issues in the care of patients with ALK-rearranged NSCLC.

Below are some highlights from Dr. Gandara’s lecture:

  • There are numerous ways to test for ALK rearrangement, aside from fluorescence in situ hybridization (FISH): immunohistochemistry (IHC), reverse transcriptase polymerase chain reaction, and tissue or cell-free plasma next-generation sequencing (NGS).
    • A proposed algorithm for ALK testing is to use IHC first, with positive (3+) and negative (0) results requiring no further testing and equivocal results (1+ or 2+) requiring further testing with either FISH or NGS.
  • Sequencing for ALK-rearranged NSCLC is an important clinical question because there are currently 4 approved ALK inhibitors—crizotinib, ceritinib, alectinib, and brigatinib—and 1 more inhibitor that may reach the US market in the near future (lorlatinib).
  • Although crizotinib has been highly successful as a first-line agent in ALK-rearranged NSCLC (response rate of approximately 65% and median progression-free survival [PFS] of approximately 10 months), progression is virtually universal. Dr. Gandara and colleagues have proposed that subtyping progression may be important to subsequent clinical decisions, with classification of systemic progression at multiple sites warranting treatment with a next-generation tyrosine kinase inhibitor (TKI) and oligo (at a single site) or central nervous system (CNS) progression (only within CNS) warranting continuation of the first-line TKI with the addition of locoregional therapy.
  • Acquired resistance in ALK-rearranged disease arises from numerous distinct mechanisms, including ALK resistance mutations, ALK amplification, and bypass pathways (KRAS, EGFR, etc.). Evidence suggests that these ALK variants have differing sensitivities to each of the ALK inhibitors.
  • The ALEX trial directly compared alectinib to crizotinib in the first-line setting for ALK-rearranged NSCLC. Dr Gandara could not discuss the results of this trial at the meeting because they were still embargoed prior to presentation at the American Society of Clinical Oncology annual meeting. However, it has now been reported that alectinib significantly prolonged PFS compared with crizotinib in this population (HR, 0.47; P <.0001) and significantly delayed CNS progression (12% vs 45%; HR, 0.16; P <.0001), suggesting that alectinib might replace crizotinib as the first-line standard of care for ALK-rearranged disease.

For additional commentary about this topic and the Oncogenic Tumor Board in Advanced NSCLC: Leveraging Actionable Mutations Along the Disease Continuum to Optimize Patient Outcomes symposium, please visit www.gotoper.com.








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