PD-L1 Combination Therapy Clinical Trials

Neal E. Ready, MD, PhD: KEYNOTE-189 was a groundbreaking study in which patients with non-squamous lung cancer received carboplatin, pemetrexed, standard histology-based chemotherapy with or without pembrolizumab. And all outcome measures were better. Overall survival, response rate, progression-free survival, and duration of response: this is a very positive trial. Certainly, in the United States this has become a major standard of care for upfront treatment of metastatic lung cancer. It does have prolonged exposure to chemotherapy, so it has 4 cycles of platinum-based chemotherapy, and then potentially going pemetrexed. It’s a groundbreaking study and a standard of care that has improved the outcome of a lot of patients with lung cancer.

The IMpower130 was another randomized trial in non-squamous lung cancer. And it was carboplatin, nab-paclitaxel, or Abraxane, with or without atezolizumab. It was a positive trial where the overall survival and other outcomes were clearly superior to chemotherapy. It is a different chemotherapy backbone than other trials in the non-squamous setting. Most of the other trials, the KEYNOTE trial and CheckMate-9LA, use pemetrexed-based treatment. It’s a positive trial, but with a different chemotherapy backbone with immunotherapy added into it.

The IMpower150 study was a more complicated study and was looking to push the envelope with treatment for non–small cell lung cancer. One of the standards of care for lung cancer, adenocarcinomas, is for platinum, a platinum chemotherapy, a taxane with bevacizumab. And a major component of this trial was to look at the Taxol, paclitaxel, bevacizumab regimen with or without atezolizumab. It did show an improvement in survival compared with the triplet backbone. It was a positive trial, FDA approved. What's not clear from this is whether the quadruplet therapy is better than, for instance, chemotherapy plus pembrolizumab or the 130 regimen of carboplatin, nab-paclitaxel, and atezolizumab. It’s a positive trial and FDA approved. Exactly where it fits in for standard of care is not entirely clear, but certainly interesting and promising therapy.

One subset analysis in this trial was particularly interesting. In general, immunotherapy does not work so well in EGFR-mutated lung cancers, for various reasons. And in this trial there were about 100 patients who were EGFR positive who were included, and the experimental regimen with atezolizumab looked better compared with the chemotherapy and bevacizumab alone. It’s a retrospective and wasn't powered to answer the question whether this was better. It has an intriguing result, and there are additional studies coming out now to test the hypothesis that this might be the best combination in EGFR-mutated lung cancer.

Transcript Edited for Clarity