Potential Role for Chemoimmunotherapy in the 2L Setting of PD-L1–High Advanced NSCLC


Centering focus on the second-line setting of PD-L1–high metastatic NSCLC, a key opinion leader defines a potential role for chemoimmunotherapy,

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 is a very a controversial discussion. We have only a few data on adding chemotherapy after progression in these patients. The data came from the EMPOWER-Lung 1 trial. Although the data are very scanty, there is a rationale to add the chemotherapy because it is able to reactivate the T-cell response and remove the myeloid suppressor components. We don’t have randomized clinical trials of adding chemotherapy after the progression post-first-line treatment, so it’s very difficult to give a final conclusion on this topic. We saw the data of the EMPOWER-Lung 1 trial, and we clearly have our own experience of adding some chemotherapy on top of the immunotherapy. It’s important to prove these results in a randomized controlled trial.

The results presented at ESMO [European Society for Medical Oncology Congress] 2022 showed that, after a median of follow-up of 33 months, the median survival with cemiplimab [Libtayo] was 23 months. Sixty-four patients continued the cemiplimab and chemotherapy as a second-line therapy. The results showed that the patients who continued in the second line resulted in a 31.3% response rate, and the median overall survival was about 15 months. Twenty-nine patients experienced serious adverse events. Here, the situation is very interesting because 31% of results and responses achieved a very high objective response rate. But we also know that the results of the chemotherapy, more or less, are 20% to 25%. We have a very good signal of continuing the cemiplimab and chemotherapy. I truly believe that we need a randomized controlled trial to compare the chemotherapy alone with the chemotherapy and cemiplimab.

I don’t have any experience using cemiplimab and chemotherapy. I’ve done this for a lot of patients in the past with our immune checkpoint inhibitors. This is something we should consider in all the patients with good performance status, and maybe they’ll progress very early after a first-line therapy with immune checkpoint inhibitors.

There’s a very important ongoing trial called the INSIGNA trial. This trial is randomizing pembrolizumab [Keytruda] alone over the chemotherapy of pembrolizumab and chemotherapy in patients with PD-L1 more than 1%. The most relevant question is whether to use the combination of chemotherapy and immunotherapy over pembrolizumab alone in patients more than 50%. The results of the meta-analysis are already very clear, and they suggest to use the combination of chemotherapy and pembrolizumab in patients between 1% and 49%. However, we know there are patients who respond very well to the single agent. Maybe with these patients in this trial, we’ll see which patients are in the gray area between 1% and 49% and if they can receive the immunotherapy alone.

Transcript edited for clarity.

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