GRACE :: Lung Cancer

Iressa

Denise Brock

ASCO 2017 – Lung Cancer – Dacomitinib Beats Iressa as First Line Treatment for EGFR Mutation-Positive NSCLC

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H. Jack West, MD
Medical Director
Thoracic Oncology Program Swedish Cancer Institute
President & CEO, GRACE
Matthew Gubens, MD
Thoracic Oncologist
Thoracic Surgery and Oncology Clinic
UCSF Helen Diller Family Comprehensive Cancer Center
Jyoti D. Patel, MD
Director Thoracic Oncology
University of Chicago Medicine

 

Drs. H. Jack West, Medical Director of the Thoracic Oncology Program at Swedish Cancer Institute in Seattle, Washington and President and CEO of GRACE, Matthew Gubens, Thoracic Oncologist at the Thoracic Surgery and Oncology Clinic of the UCSF Helen Diller Family Comprehensive Center in San Francisco, California, and Jyoti Patel, Director of Thoracic Oncology at University of Chicago Medicine gathered post meeting to discuss new information from ASCO 2017 regarding lung cancer.   In this roundtable video, the doctors discuss Dacomitinib Beats Iressa as First Line Treatment for EGFR Mutation-Positive NSCLC: New Option or Too Little Too Late?



 

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Denise Brock

ASCO 2017 – Lung Cancer – Improved Progression-Free Survival with Iressa as Adjuvant Therapy for EGFR Patients

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H. Jack West, MD
Medical Director
Thoracic Oncology Program Swedish Cancer Institute
President & CEO, GRACE
Matthew Gubens, MD
Thoracic Oncologist
Thoracic Surgery and Oncology Clinic
UCSF Helen Diller Family Comprehensive Cancer Center
Jyoti D. Patel, MD
Director Thoracic Oncology
University of Chicago Medicine

 

Drs. H. Jack West, Medical Director of the Thoracic Oncology Program at Swedish Cancer Institute in Seattle, Washington and President and CEO of GRACE, Matthew Gubens, Thoracic Oncologist at the Thoracic Surgery and Oncology Clinic of the UCSF Helen Diller Family Comprehensive Center in San Francisco, California, and Jyoti Patel, Director of Thoracic Oncology at University of Chicago Medicine gathered post meeting to discuss new information from ASCO 2017 regarding lung cancer.   In this roundtable video, the doctors discuss  Improved Progression-Free Survival with Iressa as Adjuvant Therapy for EGFR Mutation Positive Patients and Why That Doesn’t Change Anything.


 


 

 Please feel free to offer comments and raise questions in our Discussion Forums.


GRACE would like to thank the following sponsors for their support of this program

  
   
                   

 


GRACE Video

Third Generation EGFR TKIs for Acquired Resistance

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GRACE Cancer Video Library - Lung

GCVL_LU-F12_Third_Generation_EGFR_TKI_Acquired_Resistance

 

Dr. Nathan Pennell, Cleveland Clinic, discusses the concept of acquired resistance and new agents designed to address it, including Rociletinib and Merelitinib.

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Transcript

So I’d like to talk now about third generation, or mutation-specific inhibitors for epidermal growth factor receptor mutation-positive lung cancer. We know that for EGFR mutation-positive lung cancer, targeted therapy with drugs like Tarceva, Iressa, or Gilotrif are the standard of care based on trials showing they’re better than chemotherapy for improving tumor responses and the time to progression of cancer for many patients, and they can be very effective and sometimes last a long time.

Unfortunately, the majority of patients will eventually go on to develop something called acquired resistance, where the cancer begins to grow despite continued treatment with the drug that worked so well, sometimes for a long time. Something has changed in the cancer that has caused it to be resistant to the drug. When we biopsy these tumors that are progressing, what we find for EGFR mutant patients is that about 50-60% of these tumors have a new mutation, something called T790m, in exon 20. The original mutation is still there, but now it has a new mutation and this has caused the cancer to no longer respond to the Tarceva or the Gilotrif.

The good news is, there’s a whole new class of drugs available that have been specifically designed for this type of cancer, the T790m-positive cancer. These are called mutation-specific inhibitors because they inhibit only the mutant EGFR, and not the normal wild type EGFR that’s spread throughout the rest of your body. So, they tend not to have the same side effects that drugs like Tarceva or Gilotrif would have. They have less of the acne-like rash, less diarrhea; they do have different side effects. For example, one of the best known drugs is called Rociletinib, formerly CO-1686, and while it doesn’t have a rash or much diarrhea, it can raise blood sugar similar to type 2 diabetes which usually can be managed in the same way with oral drugs. The other well known drug is called AZD-9291, and one or both of these drugs is likely to be approved within the next year for T790m-positive EGFR mutant lung cancer.

Both of these have had large trials that have been presented showing that between 50% and 70% of patients with the T790m mutation will have a major response, and the vast majority of patients will have disease control, with a median time, average time, somewhere in the 8-10 month range before progression — some patients significantly longer. These are really nice options for patients who have this specific type of cancer.

Unfortunately, patients will need to have a new biopsy of their cancer at the time of developing acquired resistance, although they are trying to develop blood tests which are hopefully going to eventually replace needing a new procedure to biopsy your cancer. In 2015, for patients who develop acquired resistance, I would recommend a biopsy of the progressing cancer, and if they have T790m, enroll them on one of the clinical trials with either Rociletinib, AZD-9291, or one of the many other third generation EGFR inhibitors that are farther back in development.


Dr West

Direct Comparison of 2 EGFR Inhibitors Shows There Are Clinically Significant Differences

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At ASCO 2014, I provided the commentary after a key presentation demonstrated that the second generation EGFR tyrosine kinase inhibitor (TKI) Gilotrif (or Giotrif in some parts of the world) (afatinib) as first line therapy compared to standard chemotherapy in EGFR mutation-positive patients gave a significant benefit in overall survival (OS) that hadn’t been seen when other first generation EGFR TKIs, namely Iressa (gefitinib) or Tarceva (erlotinib) were compared to chemotherapy in EGFR mutation-positive patients. The question was whether this difference meant that Gilotrif is a significantly better EGFR TKI than Iressa or Tarceva. I noted that while these results were provocative, trials with Iressa and Tarceva were far smaller and in most cases were stopped early due to early results showing that the EGFR TKI was clearly superior in short term measures like progression-free survival (PFS) and response rate.  Accordingly, we couldn’t say anything definitive about the efficacy of one EGFR TKI vs. another by making inferences of each compared with an increasingly irrelevant comparator. If trial after trial showed that the EGFR TKI was clearly better than chemotherapy, we can’t draw meaningful conclusions of one being better based on how much stronger one looked than another against an inferior option. Instead,  the only reliable way to compare two EGFR TKIs would be to directly compare two EGFR TKIs in a randomized trial with the same eligible population.  In fact, such a trial, called LUX-Lung-7, had already been not only conceived but enrolled, randomizing EGFR mutation positive patients in Asia, Europe, Canada, and Australia to either Iressa or Gilotrif. We just needed to see how it turned out. Continue reading


GRACE Video

Emerging Options for T790M-Positive Acquired Resistance

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AR_2015_Riely_T790M_Positive_Acquired_Resistance_Options

 

Acquired resistance in EGFR patients is often driven by the T790M mutation. T790M-positive tumors respond differently to treatments than T790M-negative tumors. Dr. Greg Riely details how each status can predict patients’ responses to current treatments.

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