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Dr. Jack West is a medical oncologist and thoracic oncology specialist, and Executive Director of Employer Services at the City of Hope Comprehensive Cancer Center in Duarte, CA.

Quick Update from ASCO
Sun, 06/05/2011 - 14:08
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

I apologize if it seems that the updates about ASCO have been slow in coming. This is mostly because the lung cancer program this year has most of the higher profile presentations occurring in the second half of the meeting, which we're just getting into. And, truth be told, this isn't going to be a blockbuster year for developments in lung cancer. But let's review what we've found out about thus far.

My friend Dr. Ross Camidge from University of Colorado, who gave a terrific webinar turned into a podcast that relates the story behind ALK rearrangements and the early development of ALK inhibitor crizotib, gave the latest update of the trial that started it all and has been expanded over time. This agent still continues to prove remarkably helpful for the vast majority of patients with an ALK rearrangement who have received it, though patients do develop acquired resistance on it, as is the case with EGFR inhibitors given to patients with an ALK rearrangement. This morning, Dr. Alice Shaw from Massachusetts General Hospital also provided a comparison of the very favorable survival on the patients with an ALK rearrangement who received crizotinib to the far inferior results of ALK positive patients who weren't eligible for the trial and didn't receive crizotinib (though the fact that they weren't eligible for the trial meant that there must have been some reason(s) for them not getting crizotinib that could have also contributed to their not doing as well).

Dr. Rafael Rosell from Barcelona, Spain presented the results of the EURTAC trial of Tarceva (erlotinib) vs. standard chemo for patients with an EGFR mutation. They needed to screen 1227 patients to get to 224 patients with an EGFR mutation, and then 174 patients actually eligible for the trial. In the end, they saw the same results that have already been seen in three other very similar trials (very significantly higher progression-free survival (PFS) benefit with EGFR inhibitor therapy and a trend toward more favorable overall survival (OS) as well), and this is the first one that has shown such results in a non-Asian population. Presumably, Roche/Genentech will use these results to file for an FDA indication for first line treatment with Tarceva for EGFR mutation positive patients with an EGFR mutation.

Another trial came out of Europe (Thomas and colleagues) that randomized 224 unselected patients (not looking for EGFR mutations, nor never-smokers, etc.) with a non-squamous NSCLC to receive either cisplatin/gemcitabine/Avastin (bevacizumab) or Tarceva/Avastin as first line therapy, with PFS as the primary endpoint. The chemo/Avastin arm did significantly better than Tarceva/Avastin in terms of PFS (hazard ration (HR) 1.77, which means a 77% worse outcome on the Tarceva/Avastin arm). These results really corroborate the unfavorable results for up front EGFR tyrosine kinase inhibitor (TKI) therapy in the TORCH trial presented at ASCO last year, except that this current trial incorporated Avastin in both arms. Overall survival also favored the first line chemotherapy/Avastin arm, with a median survival of 16.3 vs. 12.6 months (HR 1.39, p = 0.0697). There is plenty more to discuss about this trial, including the remarkably good median OS of 16+ months with cisplatin/gemcitabine/Avastin, but also there was a 5-6% rate of treatment-related deaths in both arms of the study, which is higher than we're used to seeing. There are also some shortcomings in the trial, such as the fact that only 73% of patients on the first line Tarceva/Avastin arm received any further systemic therapy, as we'd really hope to give all patients an opportunity to benefit from chemo, especially in an unselected population (results for Tarceva/Avastin looked more favorable in the minority of patients with an EGFR mutation). Overall, though, these findings primarily just underscored that it is definitely NOT appropriate to give first line EGFR TKI-based therapy instead of chemotherapy-based treatment to patients who don't have a proven EGFR mutation.

There's more to discuss, but I've got to scoot to the next meeting. I'll return later to add some more quick summary information, try to address some questions on the forums, etc.

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