PD-L1 Testing and Its Role in Lung Cancer Treatment Decision-Making


Expert perspectives on the significance and limitations of PD-L1 testing in non-small cell lung cancer and the importance of integrating genomic characterization for informed treatment choices.


62-year-old woman presented to the ED with vague complaints of voice changes and cough.

  • She gave a history of a recent, 11-pound weight loss.

Past Medical, Family, and Social History

  • Hypertension, controlled with ACEi 10 mg PO QD
  • Hyperlipidemia, treated with atorvastatin 20 mg PO QD
  • COPD, treated with maintenance fluticasone furoate, umeclidinium, and vilanterol (100/62.5/25 mcg oral inhalation QD)
  • Mother: deceased at 65 years-of-age from lung cancer
  • Former smoker: 10-15 pack years. Quit tobacco habit 25 years ago.

Physical Examination

  • Current weight: 125 lbs.
  • ECOG PS 1

Diagnostic Workup

  • CT of Thorax: discovered a 4 cm nodule in the left, upper lobe
  • CT of Abdomen reveals metastases to the liver
  • MRI of Brain: negative for brain metastases

Final Pathology: consistent with squamous cell carcinoma; metastatic stage IV

PD-L1 expression by IHC: 0%

NGS: No actionable mutations


  • Therapeutic options were reviewed with the patient and family.
  • She was initiated on:
    • Nivolumab 360 mg IV Q3W + ipilimumab 1 mg/kg IV Q6W + 2 cycles of chemotherapy Q3W


Sandip P. Patel, MD: PD-L1 testing, which at the current time is done on tissue, is a key biomarker we look at in non–small cell lung cancer, both in the metastatic setting [and] increasingly in the adjuvant postsurgical setting as well. Typically, a PD-L1 test is most commonly a DAKO 22C3, which is the companion diagnostic for pembrolizumab, or VENTANA SP263, which has been a companion diagnostic for multiple anti–PD-1 and PD-L1 antibodies. Either [is] reasonable, and there’s a reasonably high incidence of concordance looking at PD-L1 expression on tumor membrane on these tissue biopsies. For those patients with PD-L1 scores greater than 50%, the opportunity for immuno-monotherapy is reasonable, meaning anti–PD-1 or anti–PD-L1 directed approaches without chemotherapy are a potential option for a subgroup of those patients.

However, some limitations are that PD-L1 in and of itself as an expression biomarker only predicts response about 47% of the time. In fact, many times patients can have high PD-L1 and in fact harbor a driver mutation for which their best therapy would actually be targeted therapy. An example would be a patient with an EGFR mutation exon 19 deletion but a PD-L1 score of 80%. The PD-L1 score will come back sooner because it’s immunohistochemistry. The next-generation sequencing can take anywhere from 2 to 3 weeks. Acting on the PD-L1 in isolation can make you want to try to treat a patient with anti–PD-1–directed monotherapy. But in fact, their best treatment is targeted therapy, which is a pill. If you try to transition from an immunotherapy to an EGFR inhibitor, there’s a risk of potentially fatal pneumonitis. And so, PD-L1 remains an imperfect biomarker. But I think it’s informative, especially for those patients who are trying to avoid chemotherapy, especially if their PD-L1 score is greater than 50%. But I think it’s important to emphasize that we should not act on PD-L1 in isolation. We also need to have the patient’s genomic characterization before we treat a patient with immunotherapy.

At the current time, the decision between single-agent immunotherapy, typically an anti–PD-1 or anti–PD-L1 agent, vs dual immunotherapy, meaning adding an anti–CTLA-4 targeting immunotherapy to an anti–PD-1 or PD-L1 backbone, is really driven by the potential net benefit of anti–CTLA-4. While we don’t have prospective randomized control studies showing a benefit in a subgroup of patients, across multiple trials, there’s been a trend that patients who receive anti–CTLA-4–based dual immunotherapy regimens who have high-risk features such as PD-L1–negative tumors, squamous histology, brain metastases, or STK11/KEAP1 mutations may preferentially benefit from introducing that anti–CTLA-4–blocking agent in addition to anti–PD-1 agent many times in combination with chemotherapy. Those are the 4 subgroups of patients I tend to consider using anti–CTLA-4 blockade with. Those patients [who] are PD-L1 negative, squamous histology, brain metastases, or STK11/KEAP1 comutation.

Transcript is AI-generated and edited for readability.

Related Videos
Edward B. Garon, MD, MS, and Anne S. Tsao, MD, experts on lung cancer
Edward B. Garon, MD, MS, and Anne S. Tsao, MD, experts on lung cancer
Edward B. Garon, MD, MS, and Anne S. Tsao, MD, experts on lung cancer
Edward B. Garon, MD, MS, and Anne S. Tsao, MD, experts on lung cancer
Joshua K. Sabari, MD, an expert on lung cancer
Joshua K. Sabari, MD, an expert on lung cancer
Joshua K. Sabari, MD, an expert on lung cancer
Joshua K. Sabari, MD, an expert on lung cancer