Considering Triplet Therapy for Nondriver NSCLC - Episode 2

Nondriver NSCLC: Adding Pembrolizumab to Platinum-Based Chemotherapy

Anne Tsao, MD:In patients with metastatic non—small cell lung cancer, and now squamous cell carcinoma, if they have high PD-L1 expression, meaning greater than 50% immunohistochemistry, then they are certainly eligible to receive pembrolizumab alone. That is certainly a very appropriate option in these patients. Where we add in a triplet combination—which is chemotherapy plus pembrolizumab, both in nonsquamous and squamous settings—is in patients who are less than 50% PD-L1 positive. Now, I will admit in my clinical practice, for patients with high PD-L1, above 50%, I have still sometimes given a triplet regimen. I do this in cases where the patient is imminently threatened, where they have extremely high tumor burden, and where I fear that if we don’t act quickly to debulk them, they’ll run into some serious trouble. Oftentimes, you have to use your clinical judgment on which patients you really need to be multiply aggressive for and give that triplet regimen because the response rates in high PD-L1 are very high, both in squamous and nonsquamous non–small cell lung cancer.

Adding pembrolizumab to chemotherapy is usually not done. More often than not, we’re adding chemotherapy to a monotherapy if it’s not acting fast enough. But in some cases, if somebody has already started on a platinum doublet and given the data from KEYNOTE-407 and KEYNOTE-189, you can add pembrolizumab to enhance a response. Certainly, if they’ve already gotten through treatment and you want to give them the immunotherapy during maintenance, that’s also an option.

KEYNOTE-189, which was close to 660 patients with non—small cell lung cancer, adenocarcinoma generally, demonstrated a significant benefit in progression-free survival. The median PFS was 8.8 months versus 4.9 months, and the hazard ratio was roughly 0.5. This was highly statistically significant. We also saw a significant increase in overall survival. In fact, the median wasn’t even reached in the triplet regimen arm. This is certainly something that we want to consider for our patients because we know that adding an immunotherapy does prolong survival, both in PFS and OS, and doesn’t appear to add too much additional toxicity to our patients.

This patient, who has metastatic adenocarcinoma of the lung, received carboplatin/pemetrexed and pembrolizumab. This would be the regimen that I would definitely choose for my patients who fit her profile. She has no prior history of any autoimmune problems. She has a relatively decent performance status and can tolerate the treatment, and she’s compliant. She also appeared to have significant disease in the liver, and that indicated to me, even though she was high PD-L1, that we wanted to try to debulk her quickly. That’s why I would agree with giving the triplet regimen in her case.

In KEYNOTE-189, across the board for all patients with nonsquamous non—small cell lung cancer, they looked at PD-L1 IHC and determined what their levels were. Across the board, across all levels, they had survival benefit. Certainly, for patients below 50% PD-L1 IHC, this is the regimen to give. If a patient is above 50%, as I mentioned before, the response rates are certainly higher, and they may have the greatest magnitude of survival benefit. So, if you have a patient who is high PD-L1, KEYNOTE-189 indicates to us that this is certainly a very appropriate regimen that can improve survival. With your choice, you do have alternatives. If this patient wanted to and was not imminently endangered by her cancer, you could consider giving her single-agent pembrolizumab. But in this case that we have before us, she was imminently threatened with huge amounts of tumor in her liver, so I certainly agree that the triplet regimen would be most appropriate for her.

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