Borghaei Shares Insight on Immunotherapy in NSCLC

Hossein Borghaei, DO, MS

Recent clinical trial findings are helping thoracic oncologists choose optimal immunotherapy treatments for their patients with non—small cell lung cancer (NSCLC), but Hossein Borghaei, DO, MS, stressed the importance of more effective biomarkers and sequencing criteria.

However, Borghaei said a good reference point is the phase III KEYNOTE-042, results of which demonstrated an improvement in overall survival (OS) with pembrolizumab (Keytruda) compared with chemotherapy for the frontline treatment of patients with locally advanced or metastatic NSCLC.

The median OS was 16.7 months with pembrolizumab monotherapy compared with 12.1 months with standard chemotherapy in patients with advanced or metastatic NSCLC and a PD-L1 tumor proportion score (TPS) ≥1% (HR, 0.81; 95% CI, 0.71-0.93; P = .0018).

Across all patients with a PD-L1 TPS of 1% to 49%, which was an exploratory analysis, the median OS was 13.4 months with pembrolizumab compared with 12.1 months for chemotherapy (HR, 0.92; 95% CI, 0.77-1.11). Overall survival correlated with greater levels of PD-L1 expression: TPS ≥50% (20 vs 12.2 months; HR, 0.69; 95% CI, 0.56-0.85; P = .0003); TPS ≥20% (17.7 vs 13.0 months; HR, 0.77; 95% CI, 0.64-0.92; P = .002).

Based on these data, the FDA granted a priority review designation to a supplemental biologics license application for pembrolizumab monotherapy for the frontline treatment of patients with locally advanced or metastatic nonsquamous or squamous NSCLC with a PD-L1 expression TPS level of ≥1% and no EGFR or ALK genomic tumor aberrations.

Borghaei added that researchers are still aiming to determine the best use of 4-drug regimens and which patients are optimal for treatment with the combination of chemotherapy and immunotherapy.

OncLive: What are some of the latest data with immunotherapy in NSCLC?

In an interview during the 2018 OncLive State of the Science Summit on Advanced Non—Small Cell Lung Cancer, Borghaei, chief, Division of Thoracic Medical Oncology, director, Lung Cancer Risk Assessment, associate professor, Department of Hematology/Oncology, Fox Chase Cancer Center, discussed immunotherapy selection in NSCLC.Borghaei: All the rage with this area has been immunotherapy combinations with chemotherapy. We are seeing some really exciting results with NSCLC, and now even in small cell lung cancer. There are a couple of issues. Many checkpoint inhibitors, mostly PD-1/PD-L1 antibodies, have been combined with chemotherapy drugs. They are all showing pretty uniform responses. There have been some varying chemotherapy backbones.

What are some factors to consider when deciding the right regimen for a patient?

There have been some data with quadruplet therapies, but we have to be careful when considering this. Four-drug regimens are not for everyone who walks through the door of your clinic. It's a thought-provoking time. For my patients, I would always use a chemotherapy backbone that I know is a little less toxic. Every time we use 2, 3, or 4 drugs, we know there is additional toxicity. The question then becomes, "Is chemotherapy plus immunotherapy for everyone?"I would say that, for a very symptomatic patient who needs aggressive therapy, a chemotherapy combination with a checkpoint inhibitor is a good idea. You're going to get a good response rate. If you have someone with metastatic disease but low tumor mutational burden, single-agent chemotherapy would work in that space. KEYNOTE-042 is a good trial to look at for reference.

What has been the biggest success thus far, and how can researchers compound this success into further advancements?

By and large, you need to look at this on a patient-by-patient basis. The field is going to evolve even more beyond this, and further research will clarify the idea of sequencing treatments and patient selection. We can hopefully get a more effective biomarker. The biggest success has definitely been identifying immunotherapy. We have 2 Nobel Prize winners in medicine for identifying checkpoint inhibitors as therapeutic targets. However, the field of immunology is very young. There is still a lot that we don't know. We're seeing wonderful clinical efficacy without understanding the biology behind it. Once we collaborate with the science side and understand how the immune system works and how we can manipulate it, this will make a huge difference.

Lopes G, Wu YL, Kudaba I, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥1%: open-label, phase 3 KEYNOTE-042 study. J Clin Oncol. 2018;36 (suppl; abstr LBA4).