Factors in Selecting First-Line Therapy for PD-L1–High Metastatic NSCLC


Comprehensive insight to factors that inform the optimal selection of first-line therapy for patients with PD-L1–high metastatic non–small cell lung cancer.

Case: A 72-Year-Old With Advanced NSCLC Cancer

Initial presentation

  • KD is a 72 y/o female who presents to her primary care physician complaining of fatigue and a persistent cough.
    • PMH:
      • Hyperlipidemia (controlled)
      • Anxiety (controlled)
      • COPD (controlled)
    • SMH: quit smoking 3 years ago and enjoys social drinking with her family
    • FH: she lives alone but her kids and grandkids live nearby

Clinical workup

  • Current Labs:
    • CBC panel: Normal
    • Liver function/Renal function: Normal
  • PD-L1: 85%
  • ECOG 1
  • Molecular testing: (-) EGFR, ALK, ROS1
  • CT scan of the head and neck showed a 5cm nodule in the right upper lobe of lung
    • CT guided biopsy of the upper lobe confirms non-squamous cell carcinoma
  • Abdominal CT scan shows liver metastases
  • Diagnosis consistent with Stage IV non-small cell lung adenocarcinoma


Marina Chiara Garassino, MD: This patient has a PD-L1 of 85%. She is a former smoker who quit 3 years ago, so she’s considered in the family of smoker patients. She’s without actionable mutations. From the results we have, the single-agent approach is perfect for this patient. However, 1 point that’s important in this patient is that has a lot of liver lesions, so to lower the risk, chemotherapy and immunotherapy can be considered.

The results from the data that we’re presenting at the ESMO [European Society for Medical Oncology] Virtual Plenary came from the Flatiron database. They showed that the single agent is always the same as the combination of chemotherapy and immunotherapy. There’s 1 exception: patients who have never smoked. For patients who have never smoked, I consider the combination with chemotherapy.

There’s also a meta-analysis that was presented by the FDA at ASCO [American Society of Clinical Oncology Annual Meeting] last year that showed that chemotherapy-immunotherapy is slightly superior to the single agent alone. But they weren’t able to identify the patients who could benefit from the chemotherapy-immunotherapy. In my practice, I treat the patient with a single agent if they have a PD-L1 that’s very high—like 85%, in this case—with 1 of the drugs that are FDA approved: pembrolizumab [Keytruda], atezolizumab [Tecentriq], or cemiplimab [Libtayo]. Any 1 is the same as the other. I consider to add to the chemotherapy only if there’s a risk of losing the patient because the burden of the tumor is too high or if the patients are never smokers.

Forty-five percent of patients are PD-L1. That’s not an absolute number because you have to count the cells that are PD-L1–positive among 100 cells. The majority of patients have a PD-L1 of more than 50%, and the majority are PD-L1 0. It’s rare to find 45%. In general, I discuss these cases with the patients. They’re between 1% and 49%. They are patients for whom the best treatment is potentially chemotherapy and immunotherapy. Clearly, they’re close to 50%, so we can also discuss monotherapy. It’s important to remember that most of the benefit for patients with more than 50% is in those patients who have 85%, like in this case, or a very high PD-L1. If it’s 45%, maybe I would treat them with a combination with chemotherapy.

Transcript edited for clarity.

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