COMMENTARY

FLAURA Data Miss the Point: PFS Matters

Mark G. Kris, MD

Disclosures

October 31, 2019

This transcript has been edited for clarity.

Hello. This is Mark Kris from Memorial Sloan Kettering, talking about recent developments in the EGFR field and particularly about the updated FLAURA survival data[1] presented at the recent European Society for Medical Oncology meeting in Barcelona.

While I did not see the presentation, the slides were shared with me. Overall, I was disappointed in the presentation, for a number of reasons.

I was not disappointed because the results were not great or because osimertinib isn't the best treatment we have for the initial treatment of patients with EGFR-mutant lung adenocarcinoma. I was disappointed because the focus was on overall survival (OS) and not progression-free survival (PFS). There was about a 7-month improvement of osimertinib over comparators for OS. The overall number, though, was about 3 years. To me, that is where the disappointment is. Despite having a drug as good as osimertinib, we're only getting about a 3-year median survival and really no long-term survivors, no cures.

I was also disappointed that we had an updated survival analysis, but we did not have an updated PFS analysis, which is more important to me because that is what patients really want. We somehow have this idea that PFS is not important and that OS is key. Of course OS is important, but the real benefit to our patients is being progression free.

A great quote was given to me by a colleague at Yale; it's by Paul Kalanithi, the author of When Breath Becomes Air, and focuses on this idea of relapsing. "Time for me is double-edged: Every day brings me further from the low of my last cancer relapse, but every day also brings me closer to the next cancer recurrence—and eventually, death."

I think this says very well what relapse means to a patient. It's devastating. The idea that PFS does not matter and that only survival matters is somewhat misplaced.

Another important thing that came out in the analysis was that 30% of patients received no additional therapy after receiving their initial therapy with osimertinib or comparator. For the other 30% that got something, only about two thirds actually got chemotherapy. That is important in that we let down a lot of our patients. For those looking at sequencing, please remember this experience, that people just don't go on to another therapy, no matter what they get.

You have to give your best drug up front. We need to think about what we can add. Data are already out there that we can add chemotherapy—and that chemotherapy can help these folks. We can add bevacizumab or ramucirumab. We can add targeted agents going against EGFR-mediated resistance like gefitinib or dacomitinib, which is now being explored in trials. We can think about adding targeted therapies for other bypass mechanisms for acquired resistance like MET or HER2. We can also think about treating oligometastases.

We need to rethink how we treat these patients. It's not about treating acquired resistance but rather it's about preventing acquired resistance. While FLAURA was great, we need to take the next step. We need to prevent acquired resistance and look at ways to treat it.

I don't want to leave this discussion saying that osimertinib isn't the drug of choice. It clearly is. It has the longest single-agent PFS, and for that reason alone, it should be used. It is associated with fewer relapses in the central nervous system and the least severe side effects. This idea that it's a better-tolerated drug opens the door to giving other therapies with it, either chemotherapy or a targeted therapy.

Remember that only one third of these patients—even those who got osimertinib—get something else. Give the best drug up front and give something with it. Giving our patients the best drug up front is the optimal way to treat cancer, and using osimertinib gives you a chance to do that.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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