Arun Krishna, AstraZeneca: Tagrisso Proven Effective at Treating NSCLC

AstraZeneca recently announced that the US Food and Drug Administration has accepted and granted Priority Review for a supplemental New Drug Application for Tagrisso (osimertinib) in combination with chemotherapy in adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The decision was based on the phase 3 FLAURA2 trial results, which extended median progression-free survival by nearly 9 months versus standard of care.

Each year, an estimated 2.2 million people are diagnosed with lung cancer globally, and 80% to 85% of patients are diagnosed with NSCLC, the most common form of lung cancer. Approximately 70% of people are diagnosed with advanced NSCLC. Priority review of Tagrisso is a step closer to providing additional options that could offer significant improvements for this patient population.

Lung Cancers Today spoke with Arun Krishna, vice president and head of the Lung Cancer Franchise for US Oncology at AstraZeneca, about what the FLAURA2 findings mean for patients with advanced lung cancer.

What are the biggest challenges related to treating advanced NSCLC?

First off, thank you so much for making the time to do this interview.

When you look at the lung cancer diagnosis, you notice that in the United States and globally, most patients are diagnosed late and they are in the metastatic setting, 70%+ of patients. That is the first challenge. When people get diagnosed with lung cancer, they’re already in a late-stage setting.

When they’re diagnosed in the late-stage setting, it is critically important that we tailor the treatments based on subtypes, whether they have a biomarker mutation, yes or no. If you’re able to do that upfront, then you have a lot of treatment options for these patients to improve their survival and help them live a meaningful life.

Talk to us about the FLAURA2 trial, beginning with its background. 

Before talking about the FLAURA2 trial, I’ll just take you back to 5 years ago when we got approval for Tagrisso as a monotherapy for patients with EGFR mutation-positive NSCLC. This was truly a game changer, both from an efficacy standpoint and from a safety and convenience standpoint.

We still believe that Tagrisso monotherapy will be the future standard of care given some of the attributes that we have already highlighted. Now, we also recognize and realize that some of these patients who are diagnosed in the metastatic setting with EGFR mutation-positive NSCLC might require a little bit more intense treatment. So, we started the trial with osimertinib with chemotherapy, which is a combination of platinum-based pemetrexed and carbo cisplatin.

How was FLAURA2 conducted, and what were the findings?

First, in terms of how the study was conducted, it was a full randomized, phase 3 study design and enrolled 700+ patients. We looked at an arm where you had Tagrisso plus chemotherapy and then compared that arm with a Tagrisso monotherapy. We were very excited to share the top-level results at the International Association for the Study of Lung Cancer World Conference on Lung Cancer earlier this year. We showed a real clinically and statistically significant benefit of the combination versus the monotherapy over 9 months, with a toxicity profile that was quite similar to the monotherapy arm.

What did you find most interesting about the findings?

As I said earlier, we believe that there are certain groups of patients who might require a more intense form of treatment. These patients are probably of ECOG status 01, they’re younger, they’re fitter. What really stood out were these 2 subtypes of patients, one with central nervous system (CNS) metastases in the brain and one with a mutation of L858R.

In this trial, in both of these subtypes where disease progression happens quite rapidly, we had a significant and very clinically meaningful benefit.

What are the clinical implications of these findings in the fight against NSCLC?

First and foremost, patients who get diagnosed in the metastatic setting do not have long to live, and we are committed to ensuring that patients in that area are able to have a long and a meaningful life. I believe that Tagrisso or osimertinib is the backbone treatment for most patients in this setting in the first line.

Now we have 2 options. We have an option for patients where they receive monotherapy based on the convenience, the overall survival benefit, et cetera, et cetera. And we have a second option for patients who require a little bit more of an intensive treatment with chemotherapy, especially the ones with CNS metastases, where you want to resolve much quicker, or with L858R. Those patients have an option as well.