COMMENTARY

Two Decades of Lung Cancer Advances

Mark G. Kris, MD

Disclosures

May 27, 2015

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Hello. It's Mark Kris from Memorial Sloan Kettering, speaking to you about the 20-year anniversary of Medscape and reflecting on how things have changed in the care of persons with lung cancer over the past 20 years.

This time has been nothing but extraordinary. It is so fundamentally different from when I began my career more than 30 years ago, accelerating particularly over the past 20 years and again over the past 10.

Major Advances in Lung Cancer Care

The most striking thing now is the number of therapies that we have. At one time there were few options for treatment. That has changed with the discovery of many new drugs and classes of drugs over the past 20 years—in particular, taxanes and pemetrexed.

The second thing that has happened is the decrease in toxicities of therapies. Twenty years ago, every patient received cisplatin. Our ability to control nausea and emesis, probably the two biggest side effects, was not as good as it is today. It's striking, now, how few patients have nausea and emesis as dose-limiting or severe toxicities. There are others we need to attack, but we've made so much progress there.

The third thing that has changed so much is the emergence of targeted therapies. We've always wanted to choose treatments that were almost sure to work for patients. We wanted to choose treatments rationally. And discovering various oncogenic drivers that lead to certain changes in cell metabolism, and coming up with drugs that specifically target those changes and negate the cancer-causing and cancer-maintaining effects of these oncogenes, has been a tremendous development.

Part of that, too, is toxicity. Again, these cancer cells are addicted to these oncogenes; normal cells, not nearly as much. So the average person receiving these targeted therapies finds them much, much better than receiving the traditional cytotoxic chemotherapies.

I don't want to throw out treatments that are extremely effective. The truth is that virtually every patient with lung cancer, including those given targeted therapies, receives cytotoxic intravenous chemotherapy at some point in their care. But now, that treatment is not the only one available, and many, many patients can live for long periods of time without those agents and without their accompanying side effects.

Even agents like pemetrexed and bevacizumab are much easier to take—so much easier than cisplatin. In many ways, the best thing about pemetrexed is that it makes cisplatin a much easier drug to give.

Last, a look to the future: It's using these drugs, particularly the targeted drugs, and trying to improve the rate of cure. We've clearly moved the median, but we haven't changed cure rates to anywhere near the degree that we want for our patients.

The Future: Better Cure Rates

We have some great opportunities. The first is the emergence of T-cell checkpoint inhibitors. These agents clearly induce important, durable, tolerable remissions. They need to be integrated quickly into the care of each and every patient. Unfortunately, we don't yet have a marker that can help us choose which patients are most likely to respond to those drugs. That's going to be the focus of research.

The second opportunity has to do with targeted therapies. The information from gastrointestinal stromal tumors (GIST) shows that we can lengthen times to recurrence and also improve survival by giving targeted therapies only to those patients who have oncogenic drivers in their tumors. Trials are now under way, and drugs are available and can be used.

This has been an extraordinary time. Where [formerly] every patient was hospitalized just to receive treatment, I now have many, many patients in my practice, under my care for years, who have never been hospitalized at all. Their lives are so much better. Their lives are much less disrupted by therapy.

But we are clearly not done. We need to cure more patients, and that needs to be our focus for the next 20 years of Medscape.

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