This activity is supported by educational grants from Astellas, AstraZeneca, Bristol-Myers Squibb, Celgene Corporation, Clovis Oncology, Foundation Medicine, Inc., Genentech, Lilly, Merck & Co., Inc., and Novartis Pharmaceuticals Corporation.
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PER Pulse™ Recap
The 10th Annual New York Lung Cancer Symposium®, which was held November 7, 2015, featured key lung cancer experts from the New York City area addressing best practices for the management of patients with lung cancer, as well as emerging therapeutic paradigms. This first of 3 PER Pulse™ Recaps from the Annual New York Lung Cancer Symposium® focuses on milestones and future directions for immunotherapy in lung cancer, as presented by Renato Martins, MD; Nasser Hanna, MD; Chandra P. Belani, MD; and David Spigel, MD.
In 2015, nivolumab and pembrolizumab became the first immune checkpoint inhibitors to be approved in patients with non–small cell lung cancer (NSCLC). As Dr Martins described, the approval of nivolumab was based on phase 3 trials demonstrating improved overall survival (OS) with nivolumab compared with docetaxel in patients with previously treated NSCLC. Ongoing phase 3 trials are examining nivolumab-based regimens in the frontline setting, in patients with early-stage or locally-advanced NSCLC, and in patients with small-cell lung cancer. Dr Hanna subsequently reviewed phase 1 data leading to accelerated approval of pembrolizumab in patients with PD-L1-expressing, previously treated NSCLC, based on the overall response rate (ORR); a subsequent phase 2/3 trial showed improved OS with pembrolizumab compared with docetaxel in patients with advanced, previously-treated NSCLC. Phase 3 trials are ongoing to examine pembrolizumab in the first-line setting in patients with metastatic NSCLC, as well as in the adjuvant setting for patients with resected disease.
Although nivolumab and pembrolizumab target PD-1, atezolizumab and durvalumab target the cognate ligand, namely PD-L1. Dr Belani described phase 2 data in patients with NSCLC, selected for PD-L1 expression, who received therapy with single-agent atezolizumab. The ORR observed in this trial has contributed to a priority review by the FDA. Dr Spigel described early-phase data with durvalumab and discussed that phase 3 trials are investigating durvalumab-based regimens in the frontline setting in patients with advanced NSCLC, as well as in patients with resected or locally-advanced disease.
The 10th Annual New York Lung Cancer Symposium®, which was held November 7, 2015, featured key lung cancer experts from the New York City area addressing best practices for the management of patients with lung cancer, as well as emerging therapeutic paradigms. This second of 3 PER Pulse™ Recaps from the Annual New York Lung Cancer Symposium® focuses on targeted agents for patients with non–small cell lung cancer (NSCLC) and molecular aberrations in the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes, as presented by Benjamin P. Levy, MD; Geoffrey R. Oxnard, MD; Helena A. Yu, MD; and Gregory J. Riely, MD, PhD.
Dr Levy summarized frontline options for patients with advanced NSCLC and activating EGFR mutations. Several options are currently approved, including the EGFR tyrosine kinase inhibitors (TKIs) erlotinib, afatinib, and gefitinib, all of which have shown improved progression-free survival and response compared with standard chemotherapy. Investigational approaches in the first-line setting include the addition of the antiangiogenic agent bevacizumab to EGFR TKIs, and the use of third-generation, T790M-targeting TKIs.
The management of acquired resistance in patients undergoing TKI therapy, specifically EGFR TKIs, was addressed by Dr Oxnard. In some cases, tumor growth is not treatment failure and patients can benefit from continued therapy; however, toxicity from therapy or the emergence of new cancer-related symptoms can be an indication to change therapy. Rebiopsy of the tumor is reasonable to determine the mechanism of resistance, and plasma-based biopsies are emerging as a less invasive method to conduct molecular testing.
In the case of T790M-negative progression, a platinum doublet is currently a standard approach for subsequent therapy. For patients with T790M-positive progression, Dr Yu described the emergence of T790M-targeting EGFR TKIs. Osimertinib was the first of these third-generation EGFR TKIs to receive accelerated approval for this setting. Due to reduced targeting of wild-type EGFR, the incidence of rash is lowered with third-generation agents compared with first- or second-generation EGFR TKIs.
Dr Riely reviewed therapeutic options for patients with NSCLC and ALK gene rearrangements. Crizotinib remains the standard first-line approach. For patients who progress on, or are intolerant of, crizotinib, ceritinib and alectinib are approved; both are also appropriate therapeutic options in the second-line setting. Additional ALK TKIs, such as lorlatinib and brigatinib, are being developed and may create additional therapeutic options for patients with ALK-rearranged NSCLC.
The 10th Annual New York Lung Cancer Symposium®, which was held November 7, 2015, featured key lung cancer experts from the New York City area addressing best practices for the management of patients with lung cancer, as well as emerging therapeutic paradigms. This third of 3 PER Pulse™ Recaps from the Annual New York Lung Cancer Symposium® focuses on current data and potential future applications for antiangiogenic agents in non–small cell lung cancer (NSCLC), as presented by Mark G. Kris, MD, and Heather Wakelee, MD.
Dr Kris discussed potential further applications for the anti–vascular endothelial growth factor (anti-VEGF) antibody bevacizumab. The results of a phase 2 study carried out in Japan, that show the addition of bevacizumab to erlotinib—an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)—improved progression-free survival (PFS) from 9.7 to 16.0 months, have been presented and await confirmation. A separate, single-arm trial combining bevacizumab with a different EGFR TKI, gefitinib, showed similar results, with a median PFS of 14.4 months achieved. The addition of bevacizumab to erlotinib in patients with mutations in the EGFR gene continues to be investigated, with an ongoing, randomized phase 2 trial being conducted in the United States and a phase 3 trial being carried out in Italy. Dr Kris also discussed bevacizumab-containing therapy outside the context of EGFR mutations; in patients with asymptomatic, untreated brain metastases, the combination of bevacizumab with carboplatin/pemetrexed yielded an intracranial response rate of 61%.
Dr Wakelee reviewed the phase 3 trial of the anti-VEGF receptor 2 (VEGFR-2) antibody ramucirumab in patients with previously treated, advanced NSCLC. The results of this trial led to the approval of ramucirumab plus docetaxel in patients with NSCLC following platinum-based chemotherapy; this application includes patients with squamous and nonsquamous histology. Ongoing investigation with antibody inhibition of VEGFR-2 includes a phase 3 trial comparing ramucirumab/erlotinib to placebo/erlotinib in patients with EGFR mutation–positive NSCLC.