Release Date: January 31, 2018
Expiration Date: January 31, 2019
Media: Internet - based
Oncology Briefing™ is an online interactive monograph that will provide an overview of recent data regarding emerging and novel treatment strategies for non-small cell lung cancer (NSCLC) with BRAF/MEK mutations. This format includes a brief presentation of clinical science and features a national thought leader, David R. Gandara, MD, who interprets it to provide key take-home points and clinical pearls for practice that will place the content into important perspective. Audio sidebars and tables provide supporting evidence.
Acknowledgment of Commercial Support
This activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.
Instructions for This Activity and Receiving Credit
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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 audio files/content until you finish the presentation.
At the end of the activity, "Educational Content/Audio Files" will be available for your reference.
In order to receive a CME 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 certificate upon completion of these steps.
This educational initiative is directed toward oncology healthcare professionals who treat patients with lung cancer, including medical oncologists, radiology oncologists, and surgical oncologists. Fellows, nurses, nurse practitioners, physician assistants, and other healthcare professionals involved in the management of patients with lung cancers are also invited to participate.
Upon completion of this activity, you should be better able to:
Outline the rationale for BRAF mutations as targets for BRAF/MEK inhibitors in NSCLC and genotyping options to identify patients who may benefit from personalized approaches
Apply key evidence concerning BRAF/MEK to inform clinical decision making in the treatment of BRAF mutation‒positive NSCLC
Describe treatment-related toxicities associates with strategies used to manage patients with BRAF/MEK mutation‒positive NSCLC
Faculty, Staff, and Planners' Disclosures
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
Disclosure: Disclosure: Consultant: Novartis.
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 activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME 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 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 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 or treatment 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)
The online Oncology Briefings™
CME activity, Exploring BRAF/MEK Inhibitors for the Treatment of NSCLC in Multiple Lines of Care
provides oncologists and other healthcare professionals with engaging instruction on the latest advances and guidelines in the treatment of BRAF
-mutated non-small cell lung cancer (NSCLC). Leading thoracic oncologist, David R. Gandara, MD, professor of medicine at the UC Davis Comprehensive Cancer Center in Sacramento, CA, summarized key clinical results and placed data into perspective. This first of 3 PER Pulse™ Recaps
from the program focuses on the role of the MAPK/ERK pathway in lung cancer:
Advances in identification of actionable oncogenic driver mutations have changed the therapeutic landscape of NSCLC. Targetable genetic alternations now include EGFR mutations ALK fusions, ROS1 rearrangements, PD-L1 expression, and now BRAF mutations.
BRAF is a serine/threonine kinase in the mitogen-activated protein kinase (MAPK) pathway. The MAPK pathway comprises multiple proteins (RAS, RAF, MEK, and ERK) that regulate transcription, gene expression, protein synthesis, cell differentiation, migration, and senescence.
The BRAF gene is mutated in approximately 7% of human cancers, including melanoma, NSCLC, and some colorectal cancers. The substitution of glutamate for valine at the 600th codon (V600E) is the most common and actionable.
The most recent National Comprehensive Cancer Network (NCCN) guidelines for NSCLC recommend testing for BRAF mutations and other predictive biomarkers before first-line therapy is initiated in patients with metastatic disease.
Dr. Gandara said: “Combination drugs against BRAF or MEK can be used to target that pathway. It’s been shown both in melanoma and now in NSCLC that using a combination strategy is more effective.”
PER Pulse Recap (2 of 3)
This second of 3 PER Pulse™ Recaps
from the program focuses on the development of BRAF and MEK inhibitors in lung cancer.
In NSCLC, BRAF and MEK combination therapy has demonstrated similar efficacy to historical melanoma trials. The majority of investigations in NSCLC have focused on the use of dabrafenib and trametinib.
The safety and efficacy of dabrafenib monotherapy and in combination with trametinib for patients with BRAFV600E-mutated, metastatic NSCLC in the first and second line was investigated in a multicohort, phase II study (BRF113928; NCT01336634).
In Cohort A, patients with BRAFV600E mutation‒positive, metastatic NSCLC who had previously relapsed or progressed following prior treatment received dabrafenib monotherapy. Patients in this arm had an ORR of 33.3%, a median duration of response (DOR) of 9.6 months, and a median progression-free survival (PFS) of 5.5 months. Further, median overall survival (OS) was reported to be 12.7 months (95% CI, 7.3-16.3).
In Cohort B, patients with BRAFV600E mutation‒positive, metastatic NSCLC who had progressed following at least 1 prior platinum-based chemotherapy received dabrafenib in combination with trametinib. Patients in this cohort had an ORR of 66.7%, a median DOR of 9.8 months, a median PFS of 10.2 months, and a median OS of 18.2 months.
In the third cohort, dabrafenib plus trametinib was investigated in patients with BRAFV600E-mutated, metastatic disease in the first line. ORR has been reported to be 61.1%, median OS has been reported to be 24.6 months, and median DOR and median PFS had not been reached at the time of this activity’s publication.
Results from this trial led to the approval of dabrafenib in combination with trametinib in patients with metastatic NSCLC with a BRAFV600E mutation, as detected by an FDA-approved test. NCCN guidelines recommend use of dabrafenib in combination with trametinib in these patients for the first and second line.
PER Pulse Recap (3 of 3)
This third and final PER Pulse™ Recaps
from the program focuses on the management of adverse events (AEs) resulting from the use of BRAF/MEK inhibitors.
Targeted therapies have improved outcomes for patients with NSCLC. However, as with any treatment, adverse events (AEs) often pose challenges to both patients and physicians.
The safety profile of dabrafenib monotherapy in NSCLC (Cohort A) is similar to that seen in patients with melanoma. The most common AEs included pyrexia (36%), asthenia (30%), and hyperkeratosis (30%). Cutaneous SCC was seen in 12% of patients, and basal cell carcinoma was seen in 5% of patients. Overall, dose interruption was required in 43% of patients, dose reductions in 18%, and treatment was discontinued in 6% of patients.
For the combination of dabrafenib plus trametinib in patients with previously treated NSCLC (Cohort B), AEs led to permanent discontinuation in 12% of patients, dose interruption in 61% of patients, and dose reduction in 35% of patients. The most common AEs included pyrexia (46%), nausea (40%), vomiting (35%), diarrhea (33%), and asthenia in 18 (32%). neutropenia (9%), hyponatremia (7%), and anemia (5%). Squamous cell carcinoma developed in 4% of patients receiving the combination.
Dr. Gandara said: “Side effects are relatively common…Reduction in dose is one strategy. The second strategy is to hold the medication for a few days until the side effect clears up and then decide whether to restart or dose reduce. We’ve learned…that patients can be managed. Most patients find a comfortable dose level that they can be kept on for many months, or sometimes even years.”
Methods to optimize toxicity management include early recognition and intervention. The AEs associated with BRAF and MEK inhibitors mostly can be managed by dose reduction or interruption. Full prescribing information for dabrafenib and trametinib should be consulted before prescribing and when considering a dose reduction.
For additional information and commentary on this topic, as well as audio and supporting text, please visit https://www.gotoper.com/online-cme-activities/oncology-briefing/oncology-briefing-exploring-brafmek-inhibitors-for-the-treatment-of-nsclc--in-multiple-lines-of-care
For information on other topics, visit gotoper.com