Non-Small-Cell Lung Cancer: Perspectives on Key Data - Episode 1

FLAURA Trial: Impact of OS Data in Advanced NSCLC


Suresh S. Ramalingam, MD, FASCO: 2019 has been another transformative year in thoracic oncology as practice-changing data continue to emerge.

In this OncLive Peer Exchange® discussion, my colleagues and I will discuss the data from the [International Association for the Study of Lung Cancer 2019] World Conference on Lung Cancer and ESMO [European Society for Medical Oncology Congress]. We will provide perspective on how the latest research will translate to patient care and your clinical practice.

I am Dr Suresh Ramalingam, a professor and deputy director at Winship Cancer Institute of Emory University School of Medicine in Atlanta, Georgia.

Today I am joined by Dr Byoung Chul Cho, a professor in the division of medical oncology at Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, South Korea; Dr Pasi Jänne, the director of the Lowe Center for Thoracic Oncology, the director of the Belfer Center for Applied Cancer Science, and a professor of medicine in the Harvard Medical School in Boston, Massachusetts; and Dr Johan F. Vansteenkiste, a professor of internal medicine at Catholic University Leuven and the head of clinic in the respiratory oncology unit at University Hospitals Leuven in Leuven, Belgium.

Thank you so much for joining us. Let’s begin. We’re here talking about a lot of exciting information that has been presented at the most recent World Conference on Lung Cancer and the ESMO conference. We want to first talk about targeted therapies. A lot of progress has been made in targeted therapies in the past few years in lung cancer. We now have at least 5 different molecular targets for which there are FDA-approved therapies, EGFR being the most common molecular abnormality for which we have targeted therapy options. We saw the overall survival results from the FLAURA study that was presented. The FLAURA study compared osimertinib with either erlotinib or gefitinib in patients with newly diagnosed advanced-stage EGFR-mutated non—small cell lung cancer.

We had already heard the PFS [progression-free survival] results of the FLAURA study earlier in the form of a presentation at ESMO Congress 2017 and subsequently as a paper in The New England Journal of Medicine. The median PFS was improved from 10.2 months in the control group to 18.9 months with osimertinib. The duration of response was almost 2-fold higher with osimertinib. Now we have the overall survival results. We now know that overall survival, which was a secondary endpoint in the FLAURA trial, was improved substantially. The median overall survival with osimertinib was 38.6 months compared with 31.8 months in the control group which was clinically and statistically significant. The median survival was improved by approximately 6.8 months for patients treated with osimertinib. This is the first time we’ve seen survival advantage with 1 TKI [tyrosine kinase inhibitor] compared with another TKI.

The other point in the FLAURA study I was struck by is the control group. The median survival for the control group is the highest recorded in contemporary EGFR clinical trials, which we think is because of the crossover of patients to receive osimertinib after they had progressed on erlotinib and gefitinib. The FLAURA study now has confirmed osimertinib’s efficacy as a frontline agent for EGFR-mutated disease. I want to get our faculty’s thoughts on how these data fit into the treatment landscape. Cho, let me ask you how you view these overall survival data, building on what we already knew about osimertinib’s efficacy in the frontline setting.

Byoung Chul Cho, MD, PhD: This is the first randomized clinical trial comparing third-generation EGFR TKI, osimertinib, and a first-generation EGFR TKI, gefitinib or erlotinib. This is also the first randomized clinical trial to demonstrate overall survival benefit with a third-generation EGFR TKI over first-generation EGFR tyrosine kinase inhibitors. I think this trial really tells us why we should use third-generation EGFR TKI, osimertinib, in advanced EGFR-mutated non—small cell lung cancer.

Suresh S. Ramalingam, MD, FASCO: Johan, when you think about the perspective of a practicing oncologist who does not necessarily specialize in lung cancer, what should they take away from the FLAURA results for their clinical practice?

Johan F. Vansteenkiste, MD, PhD: Well, in my view, this trial reinforces what we know in other settings: that it’s best to take the best therapy first. What we saw in FLAURA, as you said, is a 9-month difference in median progression-free survival. We also saw better response rate and better disease control in the brain, which is also very important in these patients because during the course of their disease, about half the patients will develop brain metastasis. If you can do something there, and you can do it with osimertinib; that’s a very important point as well. And now that there’s more overall survival data that have been presented being significantly different, this means that the 3 different endpoints of the trial—PFS as a primary and then brain control and overall survival as key secondary endpoints—are all met. This matters for a patient, and I’m especially happy that now the difference in CNS [central nervous system] control is of formal significance now. This is because what you see in the patients with EGFR-mutated non—small cell lung cancer is if they develop brain metastasis, you can manage that, but usually they’re never the same patient again. Therefore, I think giving this best drug first really is my preferred strategy.

Suresh S. Ramalingam, MD, FASCO: Thank you. Pasi, when you look at the landscape of existing EGFR TKIs, the first-generation and second-generation drugs, and osimertinib, what is the optimal rate of sequence for the plethora of agents in this setting?

Pasi A. Jänne, MD, PhD: I agree with Johan: use your best drug first. Then I think you should use this 1 with known improvement in overall survival, not just statistically but clinically, with an almost 7-month improvement. That’s pretty staggering, and I think the practice of using your best drug first should be what we would do, and I think in the US that’s what we have been doing since the approval based on the PFS. I think this further reinforces that practice pattern.

Transcript Edited for Clarity