GRACE :: Lung Cancer

Understanding Acquired Resistance in ALK+ Lung Cancer

Dr. Robert Doebele explains why he feels that repeat biopsies help researchers better understand why ALK+ lung cancer patients become resistant to current treatments – and why some do better than expected. February 2014

Continuing EGFR TKI Therapy Beyond Progression in EGFR Mutation-Positive Lung Cancer: IMPRESS Provides New Guidance

One of the major questions in the field of EGFR mutation-positive advanced NSCLC is whether we should continue patients on EGFR tyrosine kinase inhibitor (TKI) therapy as we transition to new treatment options because of acquired resistance after an initial good response.  I’ve written several posts about this always evolving question about how best to manage acquired resistance, as summarized in this FAQ, but in this post specifically about the question of whether to continue the EGFR TKI when deciding it’s time to start chemotherapy, we have been left primarily to our best judgment far more than data.  On the one hand, there is no evidence that giving an EGFR TKI concurrent with chemotherapy improves outcomes in any setting relative to chemotherapy alone, and it may just give the side effects of both chemo and the EGFR TKI, even after we now have evidence that the cancer is becoming resistant to the targeted therapy. On the other hand, we sometimes see a “flare reaction” from discontinuing a targeted therapy, even after patients are experiencing acquired resistance, and we might presume that only a subset of the cancer cells are resistant to the EGFR TKI, especially if progression is limited and somewhat slow. In that setting, perhaps it makes sense to treat the newly EGFR TKI-resistant cancer cells with chemotherapy, while continuing the EGFR TKI for the residual subset of cancer cells that seem to remain suppressed and are presumably still EGFR TKI-sensitive.

Up until now, we’ve had very little direct evidence to speak to this. A single randomized phase II trial in this setting showed no suggestion of benefit from continuing Tarceva (erlotinib) beyond progression, but that trial closed early due to weak accrual, with only 39 patients, and they were just required to have clinical benefit, not necessarily a proven EGFR mutation and clear response to first line EGFR TKI.

Halmos slide

But what we really needed was a larger, randomized phase III trial of patients with a proven EGFR mutation who were all going to be randomized to the same chemo regimen with or without ongoing EGFR TKI after acquired resistance emerged.  And we just got the first results of such a trial.

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Treating Brain Mets in ALK+ Lung Cancer

For ALK+ lung cancer patients, brain metastases are a common concern. Dr. Robert Doebele discusses the options available to treat brain mets as well as drugs that may break through the blood/brain barrier. February 2014

Are EGFR TKIs (Such as Tarceva) Effective in Lung Cancer Patients Who Are Wild Type EGFR?

For patients with wild type EGFR, meaning there is no EGFR mutation, drugs like Tarceva (erlotinib) can have a small benefit, but Dr. Joan Schiller wants research to do better. February 2014

Sym-004 Offers Hope for EGFR Wild Type Lung Cancer Patients

Eighty percent of lung cancer patients have wild type EGFR, meaning there is no EGFR mutation. Dr. Joan Schiller of UT Southwestern Medical Center discusses a new drug in development that may help those patients. February 2014

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