NCCN Guidelines Pave Way for Improving Lung Cancer Survival

Mark G. Kris, MD


January 07, 2021

This transcript has been edited for clarity.

Hello. This is Mark Kris from Memorial Sloan Kettering, speaking today about a Thanksgiving gift that I very happily learned about just a day or two before the holiday: the newest version of the NCCN guidelines. These guidelines had two very important additions, and I will get to them in just a second.

I'm still high on the Howlader paper published earlier this year in The New England Journal of Medicine that showed for the very first time that there has been a decrease in the mortality of lung cancer. Fantastic news. Even more fantastic is that the benefit is across all races and ethnicities of men and women. They specifically stated that the reason mortality has decreased in lung cancer is because of lung cancer treatment. This brings me to the new developments in the NCCN guidelines.

There are two very important additions, and I think the most important one is the addition of osimertinib as a postoperative or adjuvant therapy. On page NSCLC-4, it states that osimertinib should be added in stages IB to IIIa EGFR-mutant cancers. That is a very important development. We have talked in earlier discussions on the strength of the data from the randomized trial that showed the benefit of osimertinib over placebo with clear benefits in disease-free survival (DFS) across all groups, all stages. The critical issue with DFS here is that the goal is different. We are not looking simply for life prolongation; we are looking for the possibility of cure. And the only way you can cure someone is to put them on that DFS curve and make sure they stay on that DFS curve. Osimertinib is an important addition to help us do that. For the first time, we have a very tolerable postoperative therapy, one much more tolerable than cisplatin-based chemotherapy. I think a lot of people were deterred by that and could not recommend it because of comorbid conditions or the severity of the perceived side effects.

Another important thing is [treatment of] high-risk groups of stage IB on page NSCLC-3. I urge you to look into the fine print there. Clearly, tumors that have visceral pleural invasion, that have invasion of lymphatics or vessels, are at higher risk. Data have shown that chemotherapy is more beneficial for those patients at higher risk. For those of us that make that tough choice of who should get adjuvant chemo, please pay attention to those pathologic factors that predict high risk and help that benefit-risk ratio when recommending cisplatin-based chemotherapy. Just a reminder that the data for the osimertinib trial included patients receiving osimertinib after their chemotherapy, as well as those who didn't receive it. I think the standard of care today for a patient who is fit and could receive cisplatin-based chemotherapy is that they should get cisplatin-based chemotherapy followed by 3 years of osimertinib. The other important development is found later in the guidelines: the addition of an antibody-drug conjugate, T-DXd. It is fam-trastuzumab deruxtecan-nxki. This antibody-drug conjugate has been shown to be extremely effective as a single agent and clearly gives us a new way of treating patients with HER2-mutant disease. I think there are data also that patients who have HER2-amplified disease could benefit as well. There are data with T-DM1 that Bob Li has published, and I think ultimately we're going to see that this drug will be helpful in those patients as well.

For patients with EGFR-mutant cancers who have complete resections, adjuvant osimertinib [is recommended]. For any patient with high risk for recurrence, visceral pleural invasion, vascular invasion, lymphatic invasion, as well as those with later stages II and III, think about making sure they get chemotherapy. For people with HER2-mutant cancers, [consider] the addition of T-DXd.

Great news. I'm hoping that by adding the drugs to this adjuvant situation, we can cure more patients and make further improvements on decreasing the mortality of this disease for all patients.

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