Release Date: August 31, 2017
Expiration Date: August 31, 2018
Media: Internet - based
Community Practice Connections™: Making Critical Decisions in EGFR-Mutant Lung Cancers: How to Apply Evidence to Decide What to Do When the Patient Is There in Front of You provides case-based summaries of clinical evidence guiding therapy for patients with non–small cell lung cancers (NSCLCs) and mutations in the epidermal growth factor receptor (EGFR) gene. Clinical scenarios include first-line therapy, characterizing and treating acquired resistance, choosing subsequent lines of therapy, and managing brain metastases. Interactive clinical vignettes are followed by short video interviews with leading experts in the management of patients with lung cancers. The video interviews address decision points in the clinical vignettes, as well as questions commonly faced in the community oncology practice setting by health care professionals engaged in the care of patients with EGFR mutation-positive NSCLCs.
Acknowledgement of Commercial Support
This activity is supported by an educational grant from AstraZeneca.
CME/CE Activity Table of Contents
Module 1. EGFR Mutation-Positive NSCLC: First-Line Therapy
Module 2. Acquired Resistance to EGFR TKI Therapy
Module 3. EGFR Mutation-Positive NSCLC: Second-Line Therapy
Module 4. CNS Metastases During EGFR TKI Treatment
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.
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 are also invited to participate.
At the conclusion of this activity, you should be better prepared to:
Describe evolving roles for liquid biopsies as a method to overcome inherent challenges associated with tumor tissue testing and facilitate precision in therapeutic selection at critical decision points along the disease continuum in advanced non–small cell lung cancer (NSCLC)
Detail current and emerging strategies to personalize front-line treatment and monitor patients with advanced EGFR-mutated NSCLC
Explain clinical trial evidence concerning methods to address acquired resistance and progression in EGFR-mutated patients with advanced NSCLC
Delineate methods to manage treatment-related toxicities and central nervous system metastases in multiple lines of care for patients with advanced NSCLC
Faculty, Staff, and Planners' Disclosures
Kathryn Beal, MD
Memorial Sloan Kettering Cancer Center
New York, NY
Mark G. Kris, MD
Attending, Thoracic Oncology Service
William and Joy Ruane Chair in Thoracic Oncology
Memorial Sloan Kettering Cancer Center
New York, NY
Disclosure: Consultant: AstraZeneca.
Geoffrey R. Oxnard, MD
Physician, Thoracic Oncology
Dana-Farber Cancer Institute
Assistant Professor of Medicine
Harvard Medical School
Disclosure: Consultant: AstraZeneca, Ariad, Takeda, Inivata, Sysmex, BioRed, Chugai, Novartis.
Lecia V. Sequist, MD
The Landry Family Associate Professor of Medicine
Harvard Medical School
Director, Center for Innovation in Early Cancer Detection
Massachusetts General Hospital
Disclosure: Consultant: AstraZeneca, Ariad, Clovis, Novartis, Boehringer Ingelheim, Genentech, Bristol-Myers Squibb.
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 or nurse 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™
PER Pulse Recap (1 of 3)
This first of 3 PER PulseTM
Recaps reviews recent developments for first-line therapy, as discussed by Dr Kris.
For first-line therapy of EGFR
mutation-positive NSCLC, erlotinib, afatinib, and gefitinib are approved as single-agent therapy, and the combination of erlotinib and bevacizumab is approved in Europe.
The results of 2 phase III trials may change approaches to first-line therapy, however. ARCHER 1050 demonstrated superior progression-free survival (PFS) with dacomitinib compared with gefitinib (14.7 months vs 9.2 months; hazard ratio [HR], 0.58; P
< .0001). More recently, the FLAURA trial compared osimertinib, which also targets the T790M resistance mutation, to erlotinib or gefitinib; the primary endpoint of PFS was superior in the osimertinib arm (DL to insert PFS data after presentation at ESMO).
Additional approaches are being investigated to improve on current single-agent EGFR TKI therapy. EGF816, a next-generation TKI, is in early-phase clinical trials. Angiogenesis is also being investigated further as a therapeutic target, with bevacizumab and ramucirumab both being combined with first-generation EGFR TKIs in randomized trials.
PER Pulse Recap (2 of 3)
This second of 3 PER PulseTM
Recaps reviews the management of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs), as discussed by Drs Sequist and Oxnard.
The T790M resistance mutation is the most common cause of acquired resistance to first-line EGFR TKI therapy, occurring in approximately 50% to 60% of cases. Plasma-based testing for T790M is therefore a reasonable first approach to molecular testing upon acquired resistance. However, tissue-based testing still has a role, since a negative plasma result requires verification with a tissue biopsy. Additionally, there are other mechanisms of resistance to EGFR TKIs, including amplification of MET
genes, as well as histologic transformation to small cell lung cancer, each of which would require different therapeutic approaches.
For patients with T790M-positive acquired resistance, osimertinib is the current standard of care, based on results from the phase III AURA3 trial, which showed superior progression-free survival and overall response rate with osimertinib compared with standard chemotherapy. If a patient experiences T790M-negative progression and none of the resistance mechanisms mentioned above, chemotherapy is a reasonable option. The first-line EGFR TKI should be discontinued when switching to chemotherapy, however, due to a negative survival interaction between EGFR TKIs and chemotherapy observed in the IMPRESS trial.
PER Pulse Recap (3 of 3)
This third of 3 PER PulseTM
Recaps reviews the management of central nervous system (CNS) metastases, as discussed by Dr Beal.
Management of CNS metastases in patients with EGFR
mutation-positive NSCLC is complex, and consultation with multidisciplinary partners, including radiation oncologists, is recommended. Factors to be considered include the number and extent of brain lesions, as well as the presence or absence of symptoms.
Before the development of CNS-penetrating EGFR tyrosine kinase inhibitors (TKIs), local therapy was the main approach. A retrospective analysis of localized approaches, including stereotactic radiosurgery, showed that patients with oncogene-driven NSCLC had a median progression-free survival (PFS) of approximately 7 months after local therapy.
Systemic approaches have demonstrated efficacy against CNS metastases, particularly with the development of next-generation TKIs. An analysis of the phase III AURA3 trial of osimertinib versus chemotherapy in patients with T790M-positive disease progression showed a significantly higher CNS response rate with osimertinib (70% vs 31%; P
= .015); the PFS in the CNS was also longer in the osimertinib arm. Pulse-dosing of erlotinib, where initial dosages of 1200 mg/day are administered on the first 2 days, followed by 50 mg/day for days 3-7 each week, has shown efficacy in preventing progression of CNS metastases in patients with newly diagnosed, EGFR
For additional commentary about this topic and the Making Critical Decisions in EGFR-Mutant Lung Cancers: How to Apply Evidence to Decide What to Do When the Patient is There in Front of You
symposium, please visit www.gotoper.com