COMMENTARY

New NCCN Guidelines for Non-small Cell Lung Cancer

Mark G. Kris, MD

Disclosures

November 17, 2010

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Hi. I'm Mark Kris from Memorial Sloan-Kettering Cancer Center, and I would like to discuss the release of the latest version of the NCCN [National Comprehensive Cancer Network] Guidelines for Non-Small Cell Lung Cancer.[1] The Guidelines were posted on the NCCN Website on Friday, October 29, 2010. There are many changes throughout the Guidelines, and I refer you to the complete Guidelines for highlights of what has changed.

One area that I would like to cover now is the initial treatment of patients with stage IV non-small cell lung cancer. In this version of the guidelines, they have taken into account several recent publications that have changed the way in which we look at initial treatment. The first publication was on the use of bevacizumab with chemotherapy in patients with adenocarcinoma and large cell carcinoma, and conversely not using bevacizumab in patients with squamous cell carcinoma. The second publication suggested that outcomes are better with pemetrexed and cisplatin in patients with adeno- and large cell carcinoma, and that compared with pemetrexed and cisplatin, outcomes are better in patients with squamous cell carcinoma when they receive gemcitabine and cisplatin over pemetrexed and cisplatin. The third paper, and the one that I think changes the paradigm even more, is the trial by Tony Mok published in The New England Journal of Medicine[2] about initial gefitinib in patients with EGFR [epidermal growth factor receptor]-activating mutations. In patients receiving gefitinib, it gave them a much greater rate of response and greater progression-free survival, and now a slight increase in overall survival in patients with EGFR mutation randomly assigned to receive gefitinib instead of chemotherapy.

When you read the guidelines, the first thing that you see is the issue of whether you should do mutation testing. For patients with a pathologic diagnosis of adenocarcinoma, large cell carcinoma, or an undifferentiated carcinoma, I would urge that mutation testing be done if at all possible. Today, for patients with squamous cell carcinoma, there are insufficient data and insufficient consensus to recommend the routine testing of all tissue specimens. Although there have been scattered reports of mutations being found, they are quite uncommon -- and well below 1% overall when you put all the literature together. At this point, our efforts would be better spent to get mutation testing on all adeno-, large cell, and cancers that do not have a definition of either squamous or any of the other known types.

If the patient has an EGFR mutation, initial treatment should be with erlotinib or, where available, gefitinib. Patients with adeno- and large cell carcinoma should receive cisplatin, ideally with pemetrexed, and bevacizumab -- if indeed they are otherwise eligible, and that would mean not having hemoptysis or recent heart attack, stroke, or gastrointestinal perforation. Patients with squamous cell carcinoma should not receive bevacizumab. They should not have testing for a mutation because at this time we do not have an "actionable mutation" that we can find in squamous cell patients. They should be treated with a cisplatin combination that does not contain pemetrexed. Docetaxel and cisplatin, paclitaxel and cisplatin, or gemcitabine and cisplatin would be the drugs most available.

In patients for whom we do not have available mutation testing (and even in those patients whose clinical characteristics suggest that a mutation might be present), most experts at this point agree that these patients should receive chemotherapy if you cannot determine that a mutation is present. Please remember that in the IPASS [Iressa Pan-Asia Study] -- even if you were born in Japan, Korea, or Taiwan, or were a woman who had never smoked cigarettes -- if you did not have a mutation, your chance of benefit with gefitinib in terms of major response was only 1%. You also had an inferior progression-free survival compared with chemotherapy.

That is an update of the changes in the NCCN Guidelines. They clearly reflect the literature that has come available in the last 3 years. I urge you to read them over and see how you can fit these consensus recommendations into your practice.

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