Frontline Treatment Strategies in EGFR-Mutant NSCLC - Episode 4

Systemic Therapy Options for Non-Small Cell Lung Cancer

May 15, 2018

Heather Wakelee, MD:When a patient is newly diagnosed with adenocarcinoma of the lung, we have multiple different treatment choices now. We want to be thinking about whether or not they have a driver mutation. And if they have a driver mutation, particularlyEGFR,ALK,ROS, orBRAF, we know that starting on a targeted agent, especially forEGFRandALK, is absolutely the best approach for multiple trials. And so, we would start them on an EGFR TKI if they have anEGFRmutation. We have choices of erlotinib, gefitinib, afatinib, and now osimertinib.

There are trials looking at whether or not we could add other agents to those, like VEGF inhibitors, and we’ll wait and see what those results show. If someone has anALKtranslocation, then we can start with one of the ALK tyrosine kinase inhibitors, of which there are multiple approved—alectinib, ceritinib, crizotinib. For first-line therapy in the United States, there’s a lot of use now of alectinib, and that would be an excellent choice for our patients. The others are quite good, as well.

WithROS1, there’s a little bit more controversy, but often we would start with crizotinib or ceritinib. There are some data there, as well. WithBRAF, there’s first-line approval for the dabrafenib/trametinib combination, so we’ll often use that later.

We’ll then also be thinking about PD-L1 expression. And if someone has high PD-L1 expression, there are data to support using first-line pembrolizumab instead of chemotherapy. But there are also data now to support using chemotherapy plus pembrolizumab. And that benefit is seen across PD-L1 levels but was more so in the highest levels, so that would be the option as well. Those are all the things that we would be thinking about and the data behind it.

With the chemotherapy plus pembrolizumab, there was a clear overall survival benefit seen, as there was with pembrolizumab versus chemotherapy. With the tyrosine kinase inhibitors, it’s a little bit trickier, because there’s not always overall survival because of such high crossover rates and such high response rates. So, in trying to figure out which one to use, we have to think about the whole picture and all those various parts of information.

With squamous cell carcinoma, it’s a little bit less complicated. It’s rare to find a driver mutation, though it can happen, so we don’t look quite as much for those. With the checkpoint inhibitors, we don’t yet have clear data other than that if they’re high PD-L1, we can think about using checkpoint inhibitors. There will be more data looking at the combinations that should be coming out in 2018 that might be practice changing, but we don’t know yet. So, at this time, we’re still focusing more on chemotherapy in the squamous patients.

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