GRACE :: Lung Cancer

EML4-ALK

Dr West

Dr. Leighl’s Highlights in Lung Cancer, 2012: ALK- and ROS1-positive NSCLC

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ALK positiveDr. Leighl, lung cancer expert from Princess Margaret Hospital in Toronto, continued her summary of the leading highlights in lung cancer from 2012 with coverage of new information on XALKORI for patients with either an ALK rearrangement or the newly identified ROS-1 rearrangement.  

The video and audio versions of the podcast on this part of her program are below, along with the figures:

Dr. Leighl Highlights in LC 2012 Pt 2 ALK and ROS Rearr NSCLC Audio Podcast

Dr. Leighl Highlights in LC 2012 Pt 2 ALK and ROS Rearr NSCLC Figs

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Dr West

Lung Cancer Highlights, 2011 by Dr. Weiss, Part 2: ALK and other New Molecular Targets

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Here is the second part of the presentation on “Lung Cancer Highlights, 2011″ by Dr. Jared Weiss.  This section of his talk focuses on the striking story of the identification of the ALK rearrangement as a relevant target in lung cancer, along with an impressive treatment for this subgroup, and other new targets, such as ROS-1.  

Below you’ll find the audio and video versions of the podcast, as well as the transcript and figures.

Dr. Weiss Lung Cancer Highlights 2011, Pt 2 ALK and New Molecular Targets Audio Podcast

Dr. Weiss Lung Cancer  Highlights 2011, Pt 2 ALK and New Molecular Targets Transcript

Dr. Weiss Lung Cancer Highlights 2011 Pt 2 ALK and New Molecular Targets Figs

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Dr West

Q&A on ALK Inhibitor Therapy, with Drs. Ben Solomon and Ross Camidge

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Following the terrific presentations by Drs. Ben Solomon and Ross Camidge on the science and clinical experience with the novel ALK inhibitor XALKORI (crizotinib), we had a question and answer session, which is now available as a podcast. Here’s the audio podcast and transcript for it (not really a video component for this one).

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drs-solomon-and-camidge-qa-on-alk-inhibition-transcript

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Dr West

Dr. Ben Solomon on ALK Inhibition: From Science to Effective Treatment for ALK-Positive NSCLC

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eml4-alk-figure Several weeks ago, we were fortunate enough to be joined by not one but two international stars in lung cancer research that is being translated directly from lab bench to bedside of the patient. I don’t think there’s a more clear and inspiring example of good science leading to effective therapy, albeit for a limited patient population, than the story of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib (recently FDA approved and commercially launched as XALKORI) for patients with an EML4-ALK rearrangement (approximately 4% of the broader NSCLC population). Drs. Ben Solomon from Peter MacCallum Cancer Centre in Melbourne, Australia, and Ross Camidge from University of Colorado, in Denver, collaborated with a handful of other international researchers from all over the world to study crizotinib and conduct the critical trials, shepherding its development into a treatment now available to help a targeted subset of patients with this targeted therapy.

Dr. Ben Solomon spoke first, providing an overview of the (short) history of the EML4-ALK translocation and how crizotinib began to be studied in the first patients. He then took us on a tour of the highlights of both the efficacy data for this new agent and the side effect profile. Here’s the audio and video podcast versions of his presentation, along with pdf files of the accompanying transcript and figures:

dr-solomon-alk-inhibition-science-to-approved-therapy-audio-podcast

dr-solomon-alk-inhibition-science-to-approved-therapy-transcript

dr-solomon-alk-inhibition-science-to-approved-therapy-figures

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Dr West

Beyond XALKORI for ALK-Positive NSCLC: More Evidence of Alimta’s Activity

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The marker known as an anaplastic lymphoma kinase (ALK) translocation has been all over the lung cancer news in recent weeks, most notably in the setting of being the marker in about 4% of patients with non-small cell lung cancer (NSCLC) that is correlated with a high probability of response to the ALK inhibitor crizotinib, which was just approved by the FDA for patients whose tumors demonstrate this marker on a test in a central reference laboratory. But this marker may also be correlated with responsiveness to Alimta (pemetrexed), providing a readily available treatment option before or after these patients start crizotinib.

If this sounds familiar, it’s because I actually described such an association of particular benefit in ALK-positive NSCLC with Alimta back in February, when our friend, Dr. Ross Camidge, from the University of Colorado, published a retrospective review of patient outcomes with Alimta at the University of Colorado. They evaluated the outcomes of 89 patients tested for an EGFR mutation, KRAS mutation, or ALK translocation and also found that the median progression-free survival of their 19 ALK positive patients was significantly higher, at 9.0 months, than that seen in 37 who were wild type (WT, or “no mutation) for all three markers (4.0 months), and that neither patients with EGFR nor KRAS mutations demonstrated a significant difference compared with triple negative patients.

Though Dr. Camidge and I both noted that these results can only be taken so far, as a retrospective analysis from a single institution, these conclusions were corroborated by a remarkably similar retrospective review that comes out of Korea by Lee and colleagues, who evaluated 95 patients with advanced NSCLC and who had received Alimta as a second line or later therapy between March, 2007 and April, 2010. Specifically, they assessed outcomes as a function of whether these patients had an EGFR mutation (N = 43, or 45%), an ALK translocation (N = 15, or 16%), or WT for both (N = 37, or 39%), finding that patients with an ALK translocation had a more favorable outcome with Alimta across several endpoints. These included a significantly higher objective response rate compared to those with an EGFR mutation or WT for both (47% vs. 5% and 16%, respectively; p = 0.001), as well as disease control rate (87% vs. 26% and 57%, respectively; p < 0.001) and median time to progression (TTP) (9.2 vs. 1.5 and 2.8 months, respectively; p = 0.001).

lee-jto-2011-pfs-by-mutation (click on image to enlarge)

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