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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 2.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from AstraZeneca

Community Practice Connections™: Practical Application of Sequencing for EGFR-Mutant Lung Cancers: A Focus on Recent Evidence and Key Next Steps in Trials


Release Date: June 29, 2018
Expiration Date: June 29, 2019
Media: Internet - based
 

Activity Overview

In this case-based online activity, you will engage with physicians Veronica L.S. Chiang, MD, FAANS, Alexander Drilon, MD, Christine M. Lovly, MD, PhD, and Lynette M. Sholl, MD, to discover their approaches to treatment choices and sequencing in patients with EGFR-mutated lung cancer. Video interviews will bring key clinical trial evidence into focus, and you will gain insight into incorporating an emerging and dynamic evidence base into your daily clinical practice. The content and interviews are based on presentations delivered at Practical Application of Sequencing for EGFR-Mutant Lung Cancers: A Focus on Recent Evidence and Key Next Steps in Trials, a satellite symposium held in April 2018 adjunct to the 2018 American Association for Cancer Research (AACR) Annual Meeting, a major oncology conference in Chicago, IL. As you work through the cases, you can evaluate your approaches in relation to those of the physician faculty and review the evidence base supporting their clinical decisions.
As a busy oncologist engaged in the care of patients with lung cancer, you will have the opportunity to gain clinically relevant information that can significantly enhance the care of your patients.
Below are some clinical pearls and highlights from the activity:
  • Noninvasive assays, such as the use of cell-free plasma DNA to detect EGFR T790M mutations in patients with lung adenocarcinoma following progression or clinical resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs), are becoming an alternative to tissue biopsy for some patients.
  • For patients with EGFR mutation‒positive, advanced non-small cell lung cancer (NSCLC), the development of resistance to conventional TKI therapy remains a challenge. With third-generation TKI therapy, such as osimertinib, activity is maintained in the presence of T790M resistance.
  • There is emerging efficacy and safety evidence supporting the use of osimertinib in the first-line setting. In treatment-naïve patients with EGFR mutation‒positive, advanced NSCLC, first-line osimertinib significantly increased median progression-free survival (PFS) compared to those treated with standard TKI therapy. 

Acknowledgment of Commercial Support

This activity is supported by an educational grant from AstraZeneca.

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 program is directed toward medical oncologists and cancer researchers. Other healthcare professionals involved in the study or treatment of lung cancer are also invited to participate.

Learning Objectives

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

  1. Delineate key tumor-testing approaches utilized in clinical trials that have evaluated frontline and next-line strategies in the setting of advanced EGFR-mutated NSCLC
  2. Explain key landmark trial findings that inform therapeutic selection in the initial management of patients with advanced EGFR-mutated NSCLC
  3. Describe the impact on clinical decision making that resistance, CNS metastases, and the extent of metastases have in managing patients with advanced EGFR-mutated NSCLC
  4. Develop a personalized treatment plan for patients with advanced NSCLC to optimize outcomes and proactively manage treatment-related toxicities in multiple lines of care
Faculty

Alexander Drilon, MD
Clinical Director, Developmental Therapeutics Clinic
Assistant Attending Physician, Thoracic Oncology Service
Memorial Sloan Kettering Cancer Center
New York, NY
 

Disclosures: Consultant: AstraZeneca

Veronica L.S. Chiang, MD, FAANS
Professor of Neurosurgery
Associate Vice Chair of Academic Affairs
Director, Stereotactic Radiosurgery
Director, Gamma Knife Center
YNHH Director, Stereotactic Radiosurgery Fellowship
Yale Neurosurgery
New Haven, CT 

Disclosure: No relevant financial relationships with commercial interests to disclose.
 

Christine M. Lovly, MD, PhD
Assistant Professor of Medicine, Division of Hematology-Oncology
Co-Leader, Translational Research and Interventional Oncology Program
Vanderbilt Ingram Cancer Center
Vanderbilt University Medical Center
Nashville, TN

Disclosures: Consultant: Foundation Medicine, Cepheid, Takeda, Pfizer, AstraZeneca

Lynette M. Sholl, MD
Assistant Professor of Pathology
Harvard Medical School
Associate Pathologist, Pathology
Brigham and Women’s Hospital
Boston, MA
 

Disclosures: No relevant financial relationships with commercial interests to disclose.
 

The staff of Physicians' Education Resource®, LLC, 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 or any of the companies that provided commercial support for this activity.

PER Pulse Recap™

PER Pulse Recap (1 of 3)

The live satellite symposium continuing medical education (CME) activity, Practical Application of Sequencing for EGFR-Mutant Lung Cancers: A Focus on Recent Evidence and Key Next Steps in Trials, was held on April 16, 2018, adjunct to the 2018 American Association for Cancer Research (AACR) Annual Meeting, a major oncology conference in Chicago, IL. Expert faculty joined Alexander Drilon, MD, to discuss the recent practice-changing data and state-of-the-art approaches for patients with EGFR mutation‒positive non-small cell lung cancer (NSCLC), including how to interpret the data and incorporate the findings into clinical practice.
 
This first of 3 PER Pulse™ Recaps for the activity will focus on data supporting the use of osimertinib as first-line therapy and subsequent treatment considerations for patients who progress. Below are some highlights from the meeting featuring Dr. Lovly:
 
There is emerging efficacy and safety evidence supporting the use of osimertinib in the first-line setting.

“As osimertinib moves to the first-line setting based on the FLAURA trial, there is not an obvious response with what to do next after osimertinib relapse. Mechanisms of resistance to osimertinib are incompletely understood at this point, particularly in the first-line setting.” 
 — Christine M. Lovly, MD, PhD

FLAURA Trial
In the double-blind, phase III FLAURA trial,1 556 patients with treatment-naïve EGFR mutation‒positive, advanced NSCLC were randomized in a 1:1 ratio to receive either osimertinib (80 mg/day) or standard EGFR tyrosine kinase inhibitor (TKI) therapy (gefitinib 250 mg/day or erlotinib 150 mg/day). The primary endpoint was progression-free survival (PFS). Treatment with osimertinib significantly increased median PFS compared with those treated with standard TKI therapy (Table 1). Overall, osimertinib had a similar safety profile to standard TKI therapy. However, serious adverse events (SAEs) grade ³3 were less frequent with osimertinib treatment (34% vs 45%).


ARCHER 1050 Trial
In the phase III ARCHER 1050 trial,2 patients with newly diagnosed, advanced NSCLC and 1 EGFR mutation (exon 19 deletion or Leu858Arg) were randomized to receive either dacomitinib 45 mg/day (in 28-day cycles) or oral gefitinib 250 mg/day (in 28-day cycles) until disease progression or discontinuation. The primary endpoint was PFS.
 
Efficacy Results
Median PFS was significantly increased in patients treated with dacomitinib versus those treated with gefitinib (Table 2).


For patients with EGFR mutation‒positive, advanced NSCLC, the development of resistance to conventional TKI therapy remains a challenge. With third-generation TKI therapy, such as osimertinib, activity is maintained in the presence of T790M resistance.
However, for those patients who progress on osimertinib, the standard of care is still emerging. In the absence of a clinical trial and based on the IMpower150 data,3 expert opinion is that atezolizumab plus paclitaxel/carboplatin plus bevacizumab is a reasonable option, assuming availability, based on survival data in the subset of patients with EGFR mutation‒positive NSCLC. National Comprehensive Cancer Network guidelines recommend systemic treatment with chemotherapy for patients who progress on osimertinib.4
 
 
References
  1. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. doi: 10.1056/NEJMoa1713137.
  2. Wu YL, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(11):1454-1466. doi: 10.1016/S1470-2045(17)30608-3.
  3. Socinski MA, Jotte RM, Cappuzzo F, et al. Overall survival (OS) analysis of IMpower150, a randomized Ph 3 study of atezolizumab (atezo) + chemotherapy (chemo) ± bevacizumab (bev) vs chemo + bev in 1L nonsquamous (NSQ) NSCLC. J Clin Oncol. 2018;36(suppl; abstr 9002).
  4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-Small Cell Lung Cancer. Version 4.2018. www.nccn.org.

PER Pulse Recap (2 of 3)

As a follow-up to the live satellite symposium continuing medical education (CME) activity, Practical Application of Sequencing for EGFR-Mutant Lung Cancers: A Focus on Recent Evidence and Key Next Steps in Trials, held on April 16, 2018, in Chicago, IL, this second of 3 PER Pulse™ Recaps for the activity will focus on the use of first- and second-line treatment options in patients with EGFR mutation‒positive non-small cell lung cancer (NSCLC). Below are some highlights from the meeting featuring Dr. Drilon:
 
National Comprehensive Cancer Network guideline‒recommended choices for first-line treatment for patients with metastatic NSCLC with sensitizing EGFR mutations and performance status 0-4 include erlotinib, afatinib, or gefitinib (all category 1), and osimertinib (category 2A).1
 
Following initial therapy with a first-/second-generation(1/2G) tyrosine kinase inhibitor (TKI), approximately half of the patients who respond will develop an EGFR T790M mutation, the most common mechanism of acquired resistance to 1/2G EGFR TKI treatment. As mentioned above, osimertinib is the standard approach for these patients. For patients who progress with T790M-negative disease, 3G TKIs are not indicated and further systemic chemotherapy with a platinum doublet is the standard of care.

“In terms of standard of care, after progression, I would consider giving someone systemic chemotherapy with a platinum doublet. Something to consider given the changing landscape is whether or not we should incorporate immunotherapy in the combination of chemotherapy and I-O therapy upfront. Recent data from the IMpower study show that when you add atezolizumab to carboplatin, paclitaxel, and bevacizumab, that EGFR-mutant lung cancers can also derive benefit.”
 — Alexander Drilon, MD

IMpower150 Trial
The IMpower150 trial2 investigated carboplatin/paclitaxel with bevacizumab, atezolizumab, or bevacizumab/atezolizumab in 1202 chemotherapy-naïve patients with stage IV nonsquamous NSCLC. The coprimary endpoints were progression-free survival (PFS) and overall survival (OS). The OS analysis showed that the addition of atezolizumab to chemotherapy plus bevacizumab provided a significant OS benefit, with no new safety signals observed. With 13.5 months’ minimum follow-up, OS was improved in the chemotherapy-plus-bevacizumab/atezolizumab arm (Arm B) versus the chemotherapy-plus-bevacizumab arm (Arm C; HR, 0.78 [95% CI, 0.64-0.96]; P =.016) in the intention-to-treat (ITT) wild-type disease group (Table). Results for the subset of patients with EGFR/ALK+ or EGFR+ mutations also showed a trend toward OS benefit, although further investigation is warranted.  


References
  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-Small Cell Lung Cancer. Version 4.2018. www.nccn.org.
  2. Socinski MA, Jotte RM, Cappuzzo F, et al. Overall survival (OS) analysis of IMpower150, a randomized Ph 3 study of atezolizumab (atezo) + chemotherapy (chemo) ± bevacizumab (bev) vs chemo + bev in 1L nonsquamous (NSQ) NSCLC. J Clin Oncol. 2018;36(suppl; abstr 9002).

PER Pulse Recap (3 of 3)

As a follow-up to the live satellite symposium continuing medical education (CME) activity, Practical Application of Sequencing for EGFR-Mutant Lung Cancers: A Focus on Recent Evidence and Key Next Steps in Trials, held on April 16, 2018, in Chicago, IL, this third of 3 PER Pulse™ Recaps for the activity will focus on testing methodologies in patients with newly diagnosed, EGFR mutation‒positive non-small cell lung cancer (NSCLC). Below are some highlights from the meeting featuring Dr. Sholl:
 
Noninvasive assays, such as the use of cell-free plasma DNA to detect EGFR T790M mutations in patients with lung adenocarcinoma following progression or clinical resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs), are becoming an alternative to tissue biopsy for some patients. Plasma assays for T790M are useful in patients with acquired resistance to a first-/second-generation TKI, with a positive result sufficient to proceed with osimertinib treatment. Negative results however, should be further investigated with tissue-based testing because the sensitivity of plasma-based assays is currently only ~70% that of tissue-based testing.

“There is recognition within the community of a need to be more open-minded about the types of specimens we can test in order to ensure that every patient has an opportunity to receive an appropriate targeted therapy. One example that’s been embraced by the guidelines is the use of cytology smear preparations. These are the types of samples we often don’t consider for molecular testing, but they are a high-yield type of specimen.”
 — Lynette M. Sholl, MD

In 2013, the College of American Pathologists (CAP)/International Association for the Study of Lung Cancer (IASLC)/Association for Molecular Pathology (AMP) published a joint guideline for molecular testing in patients with lung cancer to determine sensitivity to EGFR and ALK tyrosine kinase inhibitors (TKIs).1 For patients with advanced-stage cancers with an adenocarcinoma component, the guideline recommended universal testing. In 2018, the guideline was updated, and key new recommendations are summarized below (Table).2


Updates to the 2013 recommendations include that pathologists may now use either cell blocks or other cytologic preparations as suitable specimens for lung cancer biomarker molecular testing, partly due to the advancing evidence base, as well as the development and availability of new testing methods.2
 
References
  1. Lindeman NI, Cagle PT, Beasley MB, et al. Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Arch Pathol Lab Med. 2013;137(6):828-860. doi: 10.5858/arpa.2012-0720-OA.
  2. Lindeman NI, Cagle PT, Aisner DL, et al. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment with Targeted Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Mol Diagn. 2018;20(2):129-159. doi: 10.1016/j.jmoldx.2017.11.004.
 
For additional commentary about these topics and others, visit www.gotoper.com to access more resources from the archived Practical Application of Sequencing for EGFR-Mutant Lung Cancers: A Focus on Recent Evidence and Key Next Steps in Trials.







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