New ALK Agents: Lung Cancer's 'Second Miracle'?

Giorgio V. Scagliotti, MD, PhD; D. Ross Camidge, MD, PhD


October 07, 2013

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In This Article


Giorgio V. Scagliotti, MD, PhD: Hello. I am Giorgio Scagliotti, Professor of Medical Oncology and Chief of the Department of Medical Oncology at the University of Torino at San Luigi Gonzaga Hospital in Torino. Welcome to this edition of Medscape Oncology Insights on lung cancer. Today we will highlight several relevant studies in lung cancer presented here in Amsterdam at the 13th European Cancer Congress (ECC).

Joining me for this discussion is Dr. Ross Camidge, Associate Professor and Director of the Thoracic Oncology Clinical Program at the University of Colorado, Aurora, Colorado. Welcome, Ross.

Let me start by discussing with you some of the studies on patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. You are a key opinion leader on this topic, having done relevant studies not only at the clinical level but also to help in our understanding of the biology behind this subgroup of patients.

Last year we heard the results of an important study comparing crizotinib (the first-in-class ALK inhibitor) with classic chemotherapy.[1] During the American Society of Clinical Oncology (ASCO®) meeting, you presented[2] a new ALK inhibitor, and it's not the only one. Can you review how these second-generation ALK inhibitors compare with crizotinib?

Agents Overcome Acquired Resistance

D. Ross Camidge, MD, PhD: Crizotinib works incredibly well, but everyone eventually develops acquired resistance. Approximately 50% of patients will experience disease progression in the brain. We don't think that is a change in the biology of the cancer; we think it is probably a drug penetration issue with crizotinib. In other patients, biology can change so that resistant clones are selected out from the original heterogeneity. Secondary mutations occur in the ALK gene, and there is increased ALK copy number gain in other secondary drivers, but these mechanisms are still being worked out. We have these 2 patient populations; if we could somehow get a handle on this, we might be able to give these patients a second miracle. The great thing is that there is a series of second-generation ALK inhibitors that have activity against some of the biological mechanisms of resistance, and also against brain metastases, so they are really addressing the 2 major problems.

We have seen data presented at ASCO 2013 on Novartis's LDK378.[3] The initial response rate was quoted at 80%, but now they have added more mature data, and it has come down to 57%. At this meeting, we presented data[4] on Ariad's AP26113, which has about a 61% response rate in the crizotinib-resistant population, and tomorrow we are going to see data[5] on the Roche/Chugai compound. We previously saw data on that in a crizotinib-naive population in the Far East where it had a 93% response rate, an almost unbelievably high response rate.[6] The abstract for tomorrow's presentation states that in the crizotinib-resistant population the response rate is 53%, so they are all starting to look fairly similar in that setting.


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