Joshua K. Sabari, MD
The lung cancer landscape continued to shift dramatically in 2018. Immunotherapy continued to dominate the clinical trial space, next-generation sequencing (NGS) is now regularly used in practice, and liquid biopsies began to be more widely adopted.
One of the pivotal decisions in 2018 was the FDA approval of durvalumab (Imfinzi) for the treatment of patients with locally advanced, unresectable stage III non–small cell lung cancer (NSCLC) who have not progressed following chemoradiotherapy. The decision was based on data from the PACIFIC trial, in which consolidation immunotherapy with durvalumab significantly improved progression-free survival and overall survival (OS) in patients with stage III NSCLC.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Joshua K. Sabari, MD, assistant professor, Department of Medicine, (NYU Langone’s Perlmutter Cancer Center, reflected on the rapidly advancing landscape of lung cancer.
OncLive: What data have been most impactful in lung cancer over the past year?
: In the early-stage setting is the PACIFIC trial, which looked at durvalumab after patients received concurrent chemotherapy and radiation. The results of that study were groundbreaking leading to the FDA approval and the new indication for that regimen. There was a 12-month OS benefit for patients who received durvalumab consolidation therapy after chemotherapy and radiation.
In stage IV disease, [there are] 2 very important studies that were recently presented. First was KEYNOTE-189, which is a combination of pembrolizumab (Keytruda) plus chemotherapy versus chemotherapy alone. Second was the IMpower150 trial, which is a quadruplet regimen similar to what we saw in KEYNOTE-189, but using atezolizumab (Atezolizumab) in combination with carboplatin, paclitaxel, and bevacizumab (Avastin) versus carboplatin, paclitaxel, and bevacizumab alone.
What has been the impact of combination chemotherapy and immunotherapy?
That is a controversial topic right now. There is definitely synergy, and by combining drugs that work, you may get a better response rate, a better duration of response, and better OS. What chemotherapeutics are doing specifically, are improving the immune response so the immunotherapies can recognize and attack the cancers.
Where do we stand with biomarkers of immunotherapy?
I still order PD-L1 [testing] on my patients, and I still use the cut point of 50% to define whether a patient should receive pembrolizumab alone versus pembrolizumab in combination with chemotherapy. This is for my patients with non–small cell adenocarcinoma and those with non–small cell squamous cell lung cancer. I know out in the community, people are now ordering PD-L1 expression. If you parse the data, no matter how you look at it, people who have a higher PD-L1 expression benefit with immunotherapy. What I like to do with my patients is weigh the risks and the benefits of each therapy. Why add chemotherapy to a regimen for a patient with a PD-L1 expression of 100%?
One of the other key biomarkers that is coming down the pike is tumor mutational burden (TMB). That is actually a lot more controversial right now. There are studies looking at it prospectively and retrospectively. The CheckMate-227 trial was recently presented by Matt Hellmann, MD, of Memorial Sloan Kettering Cancer Center, showing an improvement in patients who had high TMB. The controversy is, what is the definition of TMB-high? A lot of people are not using this assay and not testing for it, so we have a lot more work to do.
What is the latest with liquid biopsies?
Liquid biopsy is a novel mechanism to identify circulating tumor DNA in the peripheral blood. By doing that, we are able to identify genetic alterations that we are then able to match patients to targeted therapies. Tumors are heterogeneous, so a metastatic lesion in the lung versus a metastatic lesion in the liver might have different genetic compositions. By testing plasma or blood, we are able to identify what alterations may be circulating in the body.
What are the limitations of a traditional tissue biopsy?
Tissue remains the standard of care, as we need to define histology. But, liquid biopsy is more accessible—it is easier to do and the turnaround time is quicker. Most of our liquid biopsy assays are able to turn around in 7 to 10 days, whereas standard next-generation sequencing (NGS) takes an average of 3 weeks. We did an interesting study where we compared the actual correlation or concordance between tissue NGS and plasma NGS and we did find that if you identified an alteration in the plasma, it was identified in the tissue about 97% of the time.