Frontline Treatment Strategies in EGFR-Mutant NSCLC - Episode 2

Shifting Prognoses of Patients With EGFR-Mutant NSCLC

May 15, 2018

Heather Wakelee, MD:The prognosis for patients with advanced-stage non—small cell lung cancer has definitely been improving over time. Where we were first seeing this for patients with the driver mutations—EGFR;ALK,in particular;ROS—their natural history is a little bit different, and they were often doing better anyway. But with the tyrosine kinase inhibitors—with response rates in the majority of patients lasting oftentimes a year or longer—we were shifting to patients living longer and longer. And withEGFR, withALK, with some of the others, we now don’t have just the first group but we also have what happens when that resistance happens; we have the next groups of treatments, as well. So, that’s helping people live even longer. And we’re still having chemotherapy as an option. So, it’s not that we’re removing chemotherapy—we’re just shifting it later. It’s still an important part of treatment, and it allows us time. So, many of these patients are living a number of years.

For patients who don’t have the driver mutations, the prognosis is improving because of the checkpoint inhibitors. Again, those are not helping everybody, but they’re helping a substantial percentage of patients, particularly those who don’t have the driver mutation. So, we’ve sort of got the driver mutations figured out—we’ve still got a ways to go there. And now we’ve got immune checkpoint inhibitors, which are helping more of the other people, so kind of the whole group is shifting toward longer survival time. But it’s still time that’s often 2, 3 years.

And so, as we have patients who are newly diagnosed, it’s important to talk about: What are they looking at? And when I’m meeting a new patient…so, if this 73-year-old gentleman was my patient, we would talk about the fact that he needed to be hopeful, because there was a very high chance he was going to respond to the osimertinib he’s just started, and that that was going to work for some period of time. And I couldn’t tell him right now if that was going to be 6 months of time, a year of time, 2 years of time, or 3 years of time.

I try not to focus too much on that average, because nobody ever hits the average, but talk about the ranges. And we would talk about the fact that after that stopped working, at this point we would most likely then be able to go to chemotherapy. And I always tell people not to be too afraid of chemotherapy, because that’s a common perception. And that when the chemotherapy wasn’t working, we would likely have something else, and we would continue. And new things would be developing until such time that his body was weakened by his disease, by his treatments, and we really needed to focus more on just keeping him feeling as well as we could for the time that remained.

We also talk about the fact that there’s uncertainty. And so, this is a time in the cancer diagnosis to stop and step back and think about the things that are really important to him. What are the things he really wants to do? What if he knew he just has 6 months, what would he do? He might have much longer, but he needs to think about it from that perspective, so that he doesn’t miss out on doing the things he would do if he did have that sort of knowledge.

And then we go from there, because everybody’s journey with their disease is different, and there’s a lot of uncertainty. I also talk about the fact that just because that person is the one with cancer doesn’t mean that that’s the person in the room who’s going to go first, because something could happen to any of us unexpectedly. So, those are the conversations that we have, but it’s in that framework of the prognosis. But I think focusing too much on 1 number is really not fair to any person, because nobody knows specifically. All we know are averages from trials.

Transcript edited for clarity.

December 2017

  • A 73-year-old Caucasian man was seen in the emergency department for severe dyspnea and chest pain
  • History: symptomatic COPD managed on fluticasone and vilanterol inhaler; 50-pack/year smoking history
  • Imaging studies:
    • Chest X-Ray showed a large mass in the lung right upper lobe
    • CT of chest, abdomen, and pelvis revealed a 6.8-cm mass right-sided mass invading the chest wall, small left pleural effusion, and several small lytic lesions in the T4/5 vertebrae
  • CT-guided transthoracic needle biopsy of the lung lesion showed grade 2 adenocarcinoma
  • Molecular testing, NGS: EGFR exon 21 L858R mutation
  • Staging: T3N0M1
  • ECOG 1
  • The patient was started on osimertinib 80 mg once daily