In a few days I'll be heading back to Santa Monica, CA for the now 14th Annual Target Therapies of Lung Cancer Meeting, sponsored by the International Association for the Study of Lung Cancer (IASLC). This meeting is always an exciting one that introduces early work with an incredible array of new treatments while, on top of that, providing status updates for a few dozen agents and combinations.  How much do we cover? There are nearly 200 short presentations packed into 2.5 days, along with a few keynote lectures as well. 

Obviously, that's too much information for me to provide a synopsis of every brief talk (most are 5 minutes, a minority 10-15 minutes), but it gives you a sense of the magnitude of research being conducted on targeted therapies.  What I wanted to do now was tell you about the main topics of what we'll be discussing. I'll plan to cover many of these categories with a post summarizing some of the concepts, agents, and combinations in the weeks after the conference.

The meeting kicks off on Wednesday night with a keynote presentation by Dr. Pasi Janne from Dana Farber Cancer Institute, with whom I did my residency in Boston before I moved to Seattle. He went on to do much of the pioneering work on discovery of the activating EGFR mutations, and he'll turn to discussion of the field in 2014, including "current opportunities and challenges".  I'd bet that his talk will merit a post in its own right.

The main program begins Thursday, focusing on EGFR mutation-positive NSCLC.  We'll be covering ideas for acquired resistance, such as whether to treat with the same targeted therapy beyond progression, radiation for focal progression (a talkl being delivered by our own Dr. Weiss), and even the potential role of Iressa (gefitinib) if it might return to the US.  Of course, current questions also include second generation, irreversible EGFR inhibitors such as dacomitinib and Gilotrif (afatinib), the latter being studied with and without Erbitux (cetuximab).  And then there are even third generation EGFR inhibitors such as CO1686, AZD9291, EGFR816, and HM61713 that may prove to be effect options for patients with acquired resistance to a first generation EGFR tyrosine kinase inhibitor (TKI).

Beyond single agents, another question for managing EGFR mutation-positive NSCLC is whether combinations are more effective than single agent therapy. Combinations of various EGFR TKIS with the Met inhibitor onartuzumab (MetMAb) or crizotinib, the heat shock protein inhibitor AUY 922,  the ALK and Met inhibitor crizotinib, and several others are all being explored.

Of course, most people with lung cancer don't have an EGFR mutation, so the confrerence will then turn to treatment options for patients with EGFR wild type (no mutation). We'll discuss Erbitux with and without radiation, the monoclonal antibody necitumumab that was recently announced as improving survival combined with chemotherapy in the "SQUIRE" trial.Sym 004 is alsoa combination of EGFR-directed antibodies that is being looked at in this setting. We'll also discuss the evidence supporting approaches like the serum-based VeriStrat test, arguably useful for predicting utility of Tarceva (erlotinib) compared with chemotherapy in the EGFR wild type population.

The meeting will then shift gears to cover therapies for ALK-positive patients, including a variety of new ALK inhibitors and also heat shock protein inhibitors that areincreasingly being recognized as a potentially effectively treatment for patients with an ALK rearrangement.  There are so many of these agents being tested and presented that I'll need to cover this topic in a dedicated post after the meeting.

With several new treatments with high response rates and prolonged duration of response in the metastatic disease setting, it's appropriate to ask about the pros and cons of importing targeted therapies into earlier stage disease. We'll discuss some previously conducted and also some current trials looking at adjuvant (post-operative) EGFR or ALK inhibitors for the patients with their respective driver mutations.

 With so many potentially important targets, every year we need to ask what the best way to test should be, ranging from genomic sequencing to a test generally done in local hospitals called immunohistochemistry, to a more specialized test called fluorescence in situ hybridization (or FISH) done at regional labs, to a gene or protein signature that looks for patterns in the tumor to predict clinical behavior and/or responsiveness to treatments.

The meeting continues with an entire afternoon of discussion about a wide range of novel targets, including RET, ROS, BRAF, HER2, Met, FGFR, DDR2, IGF-1, and even more. Each of these has several drugs targeting them that is being developed for potential utility for lung cancer. With about 50 short presentations covering just this collection of novel targets, I hope you can get a sense of how much research is being done.

Amazingly, this only covers the first half of the meeting. I'll provide a preview of the second half in an upcoming part II.