PER Pulse™ Recaps for the 2nd Annual Miami Lung Cancer Conference™ focus on key topics presented at the live meeting. Overviews will describe advances in immunotherapy, antibodies to growth factor receptors, as well as continuing development in the fields of personalized medicine for patients with mutations or rearrangements in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes.
PER Pulse™ Recap
Medical Writer: David Lee, PhD
The 2nd Annual Miami Lung Cancer Conference™, held February 28, 2015, featured internationally recognized experts in thoracic malignancies. These experts, along with representatives from community practice, discussed best practices and key advances for the treatment of patients with lung cancer. This first of 2 PER Pulse™ Recaps from the Miami Lung Cancer Conference focuses on antibodies to immune checkpoint inhibitors and other oncogenic targets, as presented by Sarah Goldberg, MD, MPH, Rebecca Heist, MD, MPH, Edward Kim, MD, and Daniel Costa, MD, PhD, MMSc.
Drs. Goldberg and Heist addressed the growing body of evidence for the activity of immune checkpoint inhibitors in lung cancer. Several antibodies to PD-(L)1, including nivolumab, pembrolizumab, atezolizumab, and MEDI4736, have demonstrated single-agent activity in patients with non-small-cell lung cancer (NSCLC). In March 2015, nivolumab became the first immune checkpoint inhibitor to be approved in NSCLC, and is currently indicated for treatment of patients with pretreated, squamous NSCLC. Additionally, pembrolizumab is currently under review with the US Food and Drug Administration (FDA) for the treatment of patients with pretreated NSCLC of any histology, with a decision expected by October 2015. Several phase III trials with immune checkpoint inhibitors, both as single agents and in combination, are currently in progress.
Monoclonal antibodies to other oncogenic targets have also been approved or are currently in review. Dr. Kim summarized phase III data with ramucirumab, which targets the vascular endothelial growth factor receptor-2 (VEGFR-2). The addition of ramucirumab to docetaxel in patients with previously treated, metastatic NSCLC improved overall survival (OS), and these data resulted in FDA approval in December 2014 for patients with previously treated NSCLC of all histologies.
Dr. Costa described clinical data with necitumumab, which targets the epidermal growth factor receptor (EGFR). Two phase III trials investigated necitumumab in the first-line setting in patients with metastatic NSCLC. The trial enrolling patients with nonsquamous NSCLC was stopped early due to concerns over adverse events. However, the second trial, enrolling patients with squamous NSCLC, showed an OS benefit with the addition of necitumumab to cisplatin/gemcitabine. In July 2015, the Oncologic Drugs Advisory Committee is expected to discuss the application of necitumumab for patients in the latter setting.
The 2nd Annual Miami Lung Cancer Conference™, held on February 28, 2015, featured internationally recognized experts in thoracic malignancies. These experts, along with representatives from community practice, discussed best practices and key advances for the treatment of patients with lung cancer. This second of 2 PER Pulse™ Recaps from the Miami Lung Cancer Conference focuses on the optimal application of inhibitors of the epidermal growth factor receptor (EGFR) and the anaplastic lymphoma kinase (ALK), as presented by Edward S. Kim, MD, Heather Wakelee, MD, and Gregory Riely, MD, PhD.
Dr Kim summarized the addition of bevacizumab to EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR mutation–positive non-small-cell lung cancer (NSCLC). The current standard of care for these patients is single-agent therapy with an EGFR TKI; however, a randomized phase 2 trial from Japan demonstrated an impressive median progression-free survival (PFS) of 16.0 months with the addition of bevacizumab to erlotinib, compared with 9.7 months with erlotinib alone as first-line therapy in 154 patients with NSCLC and EGFR mutations. A randomized phase 2 trial is being carried out in the United States to confirm these results. Additionally, a single-arm phase 2 trial has investigated the addition of bevacizumab to gefitinib in 42 patients with EGFR mutation–positive NSCLC; the median PFS was 14.4 months.
While EGFR TKIs yield superior PFS compared with chemotherapy in patients with sensitizing EGFR mutations, resistance to therapy occurs after approximately 1 year of therapy. The most common mechanism of resistance is the emergence of the T790M mutation. Dr Wakelee described third-generation EGFR TKIs, such as AZD9291 and rociletinib, designed to target EGFR-T790M; these agents also spare wild-type EGFR and consequently are associated with less rash. In patients with T790M-positive disease, responses with a third-generation EGFR TKI were observed in approximately 55% to 60% of patients, with median PFS times exceeding 1 year. Phase 3 trials with these agents are currently under way.Dr Riely discussed molecularly targeted approaches for patients with ALK-positive NSCLC. For patients who have not previously received an ALK inhibitor, crizotinib is the current standard of care; however, as in EGFR mutation–positive NSCLC, disease progression eventually occurs. Next-generation ALK TKIs, such as ceritinib and alectinib, have been developed, and ceritinib has been approved by the US Food and Drug Administration for patients intolerant of or progressing on crizotinib. Importantly, these next-generation ALK TKIs also demonstrate activity in patients with brain metastases.
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