Lung Cancer

The course of Erbitux (cetuximab), the antibody to EGFR, in lung cancer over the last years has been controversial but overall underwhelming.  Added to carboplatin and Taxol (paclitaxel) or Taxotere (docetaxel) as first line therapy in a North American phase III randomized trial, it was associated with a marginal improvement in progression-free survival depending on who did the assessement, but no improvement in overall survival.

One ongoing controversy in the world of managing cancer, especially one in which cures are elusive, is how high the bar should be to guide treatment recommendations.  The "gold standard" to change treatment is a significant improvement in the primary endpoint, ideally overall survival, in a prospective, randomized phase III trial with several hundred or even several thousand people. In some settings, treatment recommendations may not even change until a few randomized phase III trials show the same significant improvement with a new treatment approach.

Almost exactly a year ago, I reported that the large MARQUEE trial of EGFR inhibitor Tarceva (erlotinib) plus either the MET inhibitor tivantinib (ARQ-197) or placebo as second or third line treatment for advanced NSCLC had been discontinued after a planned interim analysis revealed that it wouldn't be statistically significantly superior for overall survival (OS), the primary endpoint of the trial.

There are a few interesting new stories coming out of the 2013 European Society for Medical Oncology (ESMO) conference in Amsterdam that's just wrapping up today.  One has been on the  anti-PDL1 immunotherapy MPDL3280A, an agent from Roche that we saw some initial promising data on at ASCO 2013 earlier this year.  Dr.

One of the challenges we face now when a patient with a "driver mutation" like an EGFR mutation or an ALK rearrangement develops progression on a targeted therapy against that particular target is whether to continue on another agent that might work specifically against that target or switch to a less specific approach, like chemotherapy or immunotherapy, which haven't been demonstrated to be more or less effective against a specific molecularly defined subgroup.

We are in the midst of a remarkable transitional time in cancer care that is exciting but challenging, since we now have patients divided into smaller and smaller groups based on molecular markers.  Along with that, more and more patients and caregivers are participating in social media and online discussion groups.  What are the implications for these changes, and how can we use them to accelerate the pace of clinical research?  I'd like to focus on a couple of key questions for our next lung cancer tweetchat on September 26, at 8 PM Eastern, 5 PM Pacific.

Dr. Edward Garon, David Geffen School of Medicine at UCLA, covers the provocative results of the novel immune checkpoint PD-L1 inhibitor MPDL3280A in advanced NSCLC.

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Dr. Edward Garon, David Geffen School of Medicine at UCLA, reviews impressive results from the GALAXY-1 trial of the heat shock protein inhibitor ganetespib combined with combined with second line docetaxel in advanced lung adenocarcinoma.

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Dr. Edward Garon, David Geffen School of Medicine at UCLA, discusses results in a trial that demonstrated a significant survival benefit with nintedanib combined with second line docetaxel in advanced lung adenocarcinoma.

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Dr. Edward Garon, David Geffen School of Medicine at UCLA, describes the exciting developments with LDK-378 and potentially other second generation ALK inhibitors for crizotinib-resistant ALK-positive advanced NSCLC.

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