The 16th Annual International Lung Cancer Congress®, held July 30-August 1, 2015, was convened to provide current, practical information on the multidisciplinary management of lung cancer, as well as look at the novel agents and strategies that are changing the treatment of patients with lung cancer. This first of 3 PER Pulse™ Recaps from the International Lung Cancer Congress® focuses on advances in immune checkpoint inhibitors, as presented by Roy S. Herbst, MD, PhD and Ravi Salgia, MD, PhD.
Two phase III trials have recently demonstrated a survival benefit for an immune checkpoint inhibitor compared with standard chemotherapy in patients with pretreated, non-small-cell lung cancer (NSCLC). Dr. Herbst summarized that the Checkmate-017 trial showed an overall survival (OS) benefit with the anti-PD-1 antibody nivolumab compared with docetaxel (9.2 months vs 6.0 months; HR, 0.59; P <.001); the OS benefit did not appear to depend in PD-L1 expression. These data supported the US Food and Drug Administration (FDA) approval of nivolumab in March 2015 in patients with squamous NSCLC. The Checkmate-057 trial also compared nivolumab to docetaxel, but in patients with nonsquamous NSCLC. The OS was 12.2 months in the nivolumab arm and 9.4 months with docetaxel (HR, 0.73; P =.0015). Nivolumab is currently in priority review with the US FDA for the treatment of patients with nonsquamous NSCLC. On October 2, 2015, the anti-PD-1 antibody pembrolizumab was approved by the US FDA for patients with previously treated NSCLC. This indication is independent of histology; approval is specifically in patients whose disease is PD-L1 positive by a companion diagnostic test.
Dr. Salgia discussed the preliminary results of immune checkpoint inhibitors in patients with previously treated small-cell lung cancer (SCLC). Few new agents have been successfully developed in this disease despite multiple efforts; however, the high mutational burden of SCLC may favor the activity of immunotherapy. Pembrolizumab, as a single agent, was investigated in patients with PD-L1-positive SCLC. Initial data from 20 patients revealed an overall response rate (ORR) of 35%. No pneumonitis was reported, although 1 death from colitis occurred. Nivolumab, as a single agent or in combination with ipilimumab, has also been investigated in relapsed SCLC; data from 90 patients were reported. Single-agent nivolumab yielded responses in 18% of patients; the combination of nivolumab and ipilimumab initially reported an ORR of 17%, although following database lock, additional responses were reported for an updated ORR of 33%. Adverse events included grade 4 limbic encephalitis with nivolumab monotherapy; there was 1 treatment-related death due to myasthenia gravis with nivolumab (1-mg/kg dosage level) plus ipilimumab (3-mg/kg dosage level).
The 16th Annual International Lung Cancer Congress®, held July 30-August 1, 2015, was convened to provide current, practical information on the multidisciplinary management of lung cancer, as well as to look at the novel agents and strategies that are changing the treatment of patients with lung cancer. This second of 3 PER Pulse™ Recaps from the International Lung Cancer Congress® focuses on the rapid development of new tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) and the anaplastic lymphoma kinase (ALK), as presented by Glenwood D. Goss, MD, BCh, FCP(SA), FRCPC, and Sai-Hong Ignatius Ou, MD, PhD.
Dr Goss focused on next-generation EGFR TKIs. In the first-line setting, erlotinib, afatinib, and gefitinib are approved in the United States for patients with EGFR mutation–positive non–small cell lung cancer (NSCLC). Resistance eventually occurs, and approximately half of these cases are due to the T790M mutation. Osimertinib (AZD9291) and rociletinib (CO-1686) have both demonstrated activity in EGFR TKI–pretreated patients with NSCLC and the EGFR-T790M mutation, and data from both agents have been submitted to regulatory authorities for approval. Osimertinib was granted accelerated approved by the FDA on November 13, 2015, for patients with progressive, T790M-positive NSCLC progressing on an EGFR TKI. Next-generation EGFR inhibitors are being explored in the frontline setting, raising the question of whether erlotinib, afatinib, and gefitinib will remain standard approaches or if they will be replaced by next-generation agents.
Dr Ou discussed first- and second-generation ALK TKIs. The currently approved agents are crizotinib and ceritinib, used in first- and second-line settings, respectively. Next-generation ALK TKIs, including alectinib and brigatinib, are being developed to address not only the resistance that occurs with currently approved agents, but also to penetrate the blood-brain barrier, as central nervous system metastases are a frequent site of disease progression in patients with ALK-positive NSCLC. Alectinib has been granted priority review by the FDA for patients progressing on or intolerant to crizotinib; a phase 3 trial is also comparing alectinib to crizotinib in the first-line setting. Finally, it should be noted that many of the ALK TKIs, including crizotinib, ceritinib, and brigatinib, have also demonstrated activity in patients with rearrangements in the ROS1 gene.
The 16th Annual International Lung Cancer Congress®, held July 30-August 1, 2015, was convened to provide current, practical information on the multidisciplinary management of lung cancer, as well as to look at the novel agents and strategies that are changing the treatment of patients with lung cancer. This third of 3 PER Pulse™ Recaps from the International Lung Cancer Congress® focuses on the expanding settings in which antiangiogenic agents have demonstrated benefit, as presented by Paul Bunn, Jr, MD, and Paul Baas, MD, PhD.
Dr Bunn presented an overview of new agents and applications for antiangiogenic therapy in the treatment of patients with non-small-cell lung cancer (NSCLC). The phase 3 REVEL trial evaluated docetaxel with or without the anti-vascular endothelial growth factor receptor-2 (VEGFR-2) antibody ramucirumab as second-line therapy in patients with NSCLC. The addition of ramucirumab significantly increased overall survival (OS) (10.5 months vs. 9.1 months; P = .023), which led to the approval in December 2014 of ramucirumab with docetaxel as second-line therapy in patients with NSCLC of any histology.
The VEGFR tyrosine kinase inhibitor nintedanib was also examined in the second-line setting in the phase 3 LUME-Lung 1 trial. While no OS benefit was observed in the overall patient cohort, in patients with adenocarcinoma histology, the addition of nintedanib to docetaxel improved OS (12.6 months vs 10.3 months; P = .0359), leading to European approval in the latter subset.
Dr Baas described advances in therapy for patients with malignant pleural mesothelioma (MPM). A phase 3 trial carried out in France (IFCT-GFPC-0701/MAPS) evaluated the addition of bevacizumab to standard first-line pemetrexed/cisplatin in 448 patients with MPM. The primary endpoint of OS was significantly increased in the bevacizumab-containing arm compared with chemotherapy alone (18.8 months vs. 16.1 months; P = .0127). Grade 3/4 adverse events that were higher in the bevacizumab arm included hypertension (23% vs. 0) and arterial and venous thromboembolic events (6% vs. 1%). Quality-of-life measures were similar between the 2 arms, however.
For additional commentary about these topics and others, visit www.gotoper.com to access more resources from the 16th Annual International Lung Cancer Congress, including Community Practice Connections: 16th Annual International Lung Cancer Congress®