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Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. These activites are not approved for AMA PRA Category 1 Credit

Acknowledgment of Commercial Support

This activity is supported by an educational grant from AstraZeneca.


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 PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap


New Frontline Standards of Care for EGFR Mutation-Positive NSCLC

The live continuing medical education activity 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 featured key lung cancer experts Mark G. Kris, MD, Kathryn Beal, MD, Geoffrey R. Oxnard, MD, and Lecia V. Sequist, MD, describing recent therapeutic advances for patients with non–small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. 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 (18.9 months vs 10.2 months; hazard ratio [HR], 0.46; P < .0001). Fewer progression events in the central nervous system were observed in the osimertinib arm (6% vs 15%). An interim analysis of overall survival (OS) favored the osimertinib arm; however, OS results are not yet mature.

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.

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.


2 of 3
PER Pulse™ Recap

Managing Acquired Resistance to Targeted Therapy in NSCLC

The live continuing medical education activity 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 featured key lung cancer experts Mark G. Kris, MD; Kathryn Beal, MD; Geoffrey R. Oxnard, MD; and Lecia V. Sequist, MD, describing recent therapeutic advances for patients with non–small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. 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, because a negative plasma result requires verification with a tissue biopsy. Additionally, there are other mechanisms of resistance to EGFR TKIs, including amplification of MET or HER2 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.

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.


3 of 3
PER Pulse™ Recap

Managing Brain Metastases in EGFR Mutation-Positive NSCLC

The live continuing medical education activity 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 featured key lung cancer experts Mark G. Kris, MD; Kathryn Beal, MD; Geoffrey R. Oxnard, MD; and Lecia V. Sequist, MD, describing recent therapeutic advances for patients with non–small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. 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 to7 each week, has shown efficacy in preventing progression of CNS metastases in patients with newly diagnosed, EGFR mutation-positive NSCLC.

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.





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