A Chemoimmunotherapeutic Approach to Nondriver NSCLC - Episode 1

Diagnosing a Case of Nondriver Metastatic NSCLC

Mark A. Socinski, MD:Our case today is of a 66-year-old gentleman who had a history of smoking, 30-pack per year exposure in the past. He presented with 1 to 2 months of increasing cough and shortness of breath, and he does attest to the fact that he had had some intermittent hemoptysis. He saw his primary care physician who obtained a chest x-ray followed by a chest CT that showed a 3-cm left upper lobe mass with evidence of some mediastinal adenopathy as well as left-sided pleural effusions, some pleural thickening.

He underwent a biopsy that included one of the lymph nodes as well as the pleural involvement that showed an adenocarcinoma. He was appropriately tested for the recommended oncogenic drivers, all of which were negative. And appropriately so, he had a PD-L1 [programmed-cell death ligand 1] immunohistochemical test that showed him to be 45% positive.

He also had an abdominal CT [computed tomography] that showed no evidence of disease in the abdomen. He had a brain MRI [magnetic resonance imaging] that showed no evidence of brain metastases. So, he was staged as a stage IVa because of the pleural involvement. And he was initially started on a regimen of carboplatin, pemetrexed, and pembrolizumab for stage IV adenocarcinoma of the lung, nononcogenic driver, and 45% PD-L1—positive.

Patients with lung cancer very commonly have a history that includes several months of a symptom, whether it be cough or shortness of breath, sometimes chest pain. Sometimes the diagnosis is delayed because many of these people are felt to have bronchitis, maybe early, what we used to refer to as walking pneumonia. And they would be treated with the course of antibiotics, sometimes 2 courses of antibiotics, obviously because you weren’t really treating an infection, you were treating lung cancer. With an antibiotic, their symptoms would not resolve.

And so, my experience has been that there is often a delay in doing an initial chest x-ray, which clearly would have shown the abnormality in this gentleman, and it did when he eventually had a chest x-ray. Obviously, a chest x-ray would lead to a chest CT. In a 66-year-old gentleman with a 30-pack per year history of smoking, you have to be suspicious that with the right radiographic appearance, certainly his clinical presentation of cough, some hemoptysis, shortness of breath is very consistent with lung cancer. And then you know obviously with the right radiographic findings, which this gentleman did have, you’d have to be highly suspicious that this is a new primary lung cancer. And the things that are important to establish are the stage of the lung cancer. And given his pleural involvement, that would make him stage IV, and then the diagnosis.

And the diagnosis here is adenocarcinoma, and that’s the most common diagnosis we see arising from the lung. And I tout that part of the diagnostic evaluation of an adenocarcinoma today is a complete genomic profiling with the usual oncogenic drivers, and a PD-L1 immunohistochemical stain as standard of care in this population. So, he was appropriately evaluated, and we have a good idea. He does not have an oncogenic driver. And it’s appropriate for him with 45% PD-L1 positivity to receive the combination of chemotherapy plus immunotherapy, which is what would happen with this gentleman.

Lung cancer screening is an important part of our primary care medicine. We have evidence from the lung cancer screening trial that annual low-dose viral CT scans in the population of over the age of 50 with at least a 30-pack per year history of smoking, which this gentleman does have both of those features, reduces lung cancer mortality by diagnosing lung cancer at an earlier stage.

Now this gentleman had symptoms. So, he would not have typically been thought of as a screening patient, he had a symptom so he really received these tests in a diagnostic manner, if you will. But let’s say he was completely asymptomatic. Then, yes, his primary care physician should have educated him and recommended that he have lung cancer screening with a low-dose viral CT to reduce his chance of dying of lung cancer.

Transcript edited for clarity.


A 66-Year-Old Man With NSCLC

May 2018: H&P

  • A 66-year-old man presented to primary care with complaints of persistent cough and shortness of breath with easy exertion.
    • PE: Average height, very thin (BMI = 18 kg/m2); says he has been losing weight although not dieting; mild fever (100.6 degrees); intermittent hemoptysis
    • Lab results: CrCL 75 mL/min; A1C 6.8%; WBC 15K/µL
    • PMH: HTN managed on atenolol; former smoker (30 pack-years); attributes cough to smoking but has persisted for 3 years now since he quit
  • Primary care suspected bronchitis and prescribed amoxicillin; referred to pulmonology

June 2018: Pulmonology evaluation

  • Pulmonologist evaluated patient for COPD: diminished lung function on spirometry
  • CT revealed a 3-cm mass in left lung and multiple (<2 cm) masses in right lung, pleura, and axial lymph nodes; patient referred to oncology.

July 2018: Oncology exam

  • Biopsy identified adenocarcinoma in left lung with lymph node and pleural involvement
  • Molecular testing:
    • ALK& ROS1 rearrangement, negative
    • EGFR, KRAS wild-type
    • KRAS negative
    • PD-L1 TPS: 45%
  • Additional testing: Abdominal CT, NED; Brain MRI, NED
  • Diagnosis: Stage IVA lung adenocarcinoma without molecular drivers

August 2018

  • Patient begins treatment with pemetrexed/carboplatin plus pembrolizumab 200 mg q3 wks