Search Videos by Topic or Participant
Browse by Series:

Development of ALK Inhibitors in Advanced NSCLC

Panelists: Mark G. Kris, MD, MSKCC; Corey J. Langer, MD, Penn; Benjamin P. Levy, MD, Mount Sinai;Mark A. Socinski, MD, UPMC; Heather A. Wakelee
Published: Tuesday, Apr 01, 2014
For High-Definition, Click
The ALK inhibitor crizotinib initially gained accelerated approval from the FDA in August 2011 based on an improvement in objective response rates (ORR) for patients with ALK-positive non-small cell lung cancer (NSCLC). In November 2013, crizotinib was granted a full regulatory approval based on an improvement in PFS and ORR when compared with chemotherapy in a phase III study.

The approval of crizotinib was a game-changer in the treatment of NSCLC, notes Mark G. Kris, MD. Moreover, data has indicated that continuing crizotinib after disease progression may improve survival for patients with advanced ALK-positive NSCLC, notes Kris. This is particularly true in the case of oligoprogression, notes Corey J. Langer, MD. In addition to patients with ALK translocations, crizotinib also appears effective in patients with MET amplifications and ROS1 alterations.

At this point, the mechanism of resistance to ALK inhibition remains unclear, notes Kris. As a result, it is difficult to ascertain whether new ALK inhibitors are truly effective in patients who are resistant or if they are just more potent. The investigation of resistance in this setting is complicated, since the mechanism appears to be heterogeneous, notes Mark A. Socinski, MD.

The side effect profile for crizotinib has become familiar since the 2011 approval, particularly the management of GI toxicities. In most situations, these side effects can be ameliorated by dose reductions, notes Socinski. In studies comparing the two agents, it appears that the ALK inhibitor ceritinib (LDK378) may have more GI toxicity than crizotinib, suggests Langer.


Slider Left
Slider Right
For High-Definition, Click
The ALK inhibitor crizotinib initially gained accelerated approval from the FDA in August 2011 based on an improvement in objective response rates (ORR) for patients with ALK-positive non-small cell lung cancer (NSCLC). In November 2013, crizotinib was granted a full regulatory approval based on an improvement in PFS and ORR when compared with chemotherapy in a phase III study.

The approval of crizotinib was a game-changer in the treatment of NSCLC, notes Mark G. Kris, MD. Moreover, data has indicated that continuing crizotinib after disease progression may improve survival for patients with advanced ALK-positive NSCLC, notes Kris. This is particularly true in the case of oligoprogression, notes Corey J. Langer, MD. In addition to patients with ALK translocations, crizotinib also appears effective in patients with MET amplifications and ROS1 alterations.

At this point, the mechanism of resistance to ALK inhibition remains unclear, notes Kris. As a result, it is difficult to ascertain whether new ALK inhibitors are truly effective in patients who are resistant or if they are just more potent. The investigation of resistance in this setting is complicated, since the mechanism appears to be heterogeneous, notes Mark A. Socinski, MD.

The side effect profile for crizotinib has become familiar since the 2011 approval, particularly the management of GI toxicities. In most situations, these side effects can be ameliorated by dose reductions, notes Socinski. In studies comparing the two agents, it appears that the ALK inhibitor ceritinib (LDK378) may have more GI toxicity than crizotinib, suggests Langer.
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Updates in Novel Therapeutic Options for Lung Neuroendocrine TumorsMay 31, 20181.0
Community Practice Connections™: Working Group to Optimize Outcomes in EGFR-mutated Lung Cancers: Evolving Concepts for Nurses to Facilitate and Improve Patient CareJun 30, 20181.5
Publication Bottom Border
Border Publication
x