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Accreditation/ Credit Designation

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 Boehringer Ingelheim Pharmaceuticals, Inc.


Oncogenic Tumor Board in Advanced NSCLC: Leveraging Actionable Mutations Along the Disease Continuum to Optimize Patient Outcomes PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap


1 of 3
PER Pulse™ Recap

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.

2 of 3
PER Pulse™ Recap

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.

3 of 3
PER Pulse™ Recap

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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