Considering Triplet Therapy for Nondriver NSCLC - Episode 1

Approaching Therapy for a Case of Nondriver NSCLC

Anne Tsao, MD:This is a case of a 64-year-old lady who has had dyspnea on exertion for the past 2 years. Most recently, her symptoms became more prominent when at rest, so she decided to seek some medical attention. Now, she did go see her primary care physician, and she was found on physical examination to have decreased breath sounds predominantly in the right lung. She isn’t exactly of great performance status, perhaps ECOG PS1. In her past medical history, she has some mild hypertension managed on lisinopril, but other than that, she was not really on any other medications.

Now, she does have a 15-pack-year smoking history and is trying to quit. Her CT scan shows 2 masses in the right upper lobe and several masses in the liver. On her biopsy of the right lung mass, it looks like she has an adenocarcinoma. There is a mutation profile that is run. She isEGFRnegative, as well asALKIHC negative. She’s alsoROS1negative andKRASnegative. But when her PD-L1 is tested, she’s 56% on IHC. Now, her PET/CT scan also demonstrated the lung masses in the right upper lobe as well as multiple masses in the liver. The brain MRI is negative for any metastatic disease. She has a stage 4 adenocarcinoma of the lung, and she’s initiated on carboplatin/pemetrexed and pembrolizumab. This is a pretty typical case of what walks in your door for a new diagnosis of metastatic adenocarcinoma of the lung.

In our patients with lung cancer, we always get a smoking history because it is quite relevant. Nowadays, with immunotherapies, we do know that current smokers and former smokers actually have a good response to these immunotherapies. It may have something to do with tumor mutational burden. But there are a lot of hypotheses as to why that might be. It would also be very relevant if she were a never-smoker or a minimal former smoker because we know that those patients can carry oncogenic driver mutations, which would be very useful in understanding what to give as optimal therapy.

In patients with stage 4 adenocarcinoma of the lung, now there are several options. In the past, we used to recommend a platinum doublet with or without bevacizumab if they were eligible for bevacizumab. Now we have several options. In the case of metastatic adenocarcinoma, we have this triplet regimen: carboplatin/pemetrexed and pembrolizumab followed by pemetrexed/pembrolizumab maintenance therapy. Now, this is a new regimen. It was recently published in theNew England Journal of Medicine, KEYNOTE-189, and it shows significant survival benefit over a platinum doublet.

For patients who don’t have an oncogenic driver mutation, the prognosis is still grim. This is still a terminal disease, so we clearly do need better therapies. We definitely have some advances with immunotherapies, but this doesn’t seem to benefit all our patients yet. So, there certainly still is a knowledge gap, and we have to continue to do clinical trials to prolong life for our patients.

Transcript edited for clarity.

A 64-Year-Old Woman With Metastatic NSCLC

  • A 64-year-old woman reported having cough and shortness of breath on exertion for the past 2 years, but now having persistent symptoms even without exertion.
    • PE: revealed diminished breath sounds and minimal expiratory wheezing in right lung; not physically fit
    • PMH: mild hypertension well managed on lisinopril
    • SH: smoker, 15 pack-years
  • CT scan revealed 2 masses in RUL and several small masses in the liver
  • Biopsy of right lung mass confirmed grade 2 adenocarcinoma
    • EGFRnegative,KRASnegative
    • IHC negative forALK-rearrangement,ROS1-rearrangement
    • PD-L1 TPS: 56%
  • PET scan showed multiple areas of FDG uptake in liver, SUVmax, 7.8
  • Brain MRI, negative for metastases
  • Diagnosis: stage IV lung adenocarcinoma
  • Patient started on treatment with pembrolizumab/pemetrexed/carboplatin