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State of Immunotherapy Continues to Shift in NSCLC

Caroline Seymour
Published: Friday, Jul 13, 2018

Liza C. Villaruz, MD
Liza C. Villaruz, MD
The KEYNOTE-024 trial may have positioned pembrolizumab (Keytruda) as the frontline treatment for patients with PD-L1–overexpressing tumors, but there have been many other trials that have followed suit, explained Liza C. Villaruz, MD. Additionally, other studies continue to showcase combination immunotherapy’s potential in the first-line setting.

In KEYNOTE-024, the median overall survival (OS) was 30.2 months versus 14.2 months with chemotherapy, reflecting a 37% reduction in the risk of death (HR, 0.63; 95% CI, 0.47-0.86; P = .002).1

The KEYNOTE-042 trial later explored the role of pembrolizumab in patients with a PD-L1 expression level ≥1%. Although OS was linked to higher levels of PD-L1 expression, the single-agent outperformed standard of care chemotherapy regardless of stratification: tumor proportion score (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); and TPS ≥1% (16.7 vs 12.1 months; HR, 0.81; 95% CI, 0.71-0.93; P = .0018).2

In the CheckMate-026 trial, single-agent nivolumab (Opdivo) did not improve progression-free survival or OS compared with chemotherapy in the frontline setting for patients with PD-L1–positive NSCLC. However, patients enrolled in CheckMate-026 had PD-L1 expression on ≥5% of tumor cells—a much broader range than in the successful KEYNOTE-024 trial of single-agent pembrolizumab. Patients with tumors showing ≥50% PD-L1 were selected for that study. Further, although CheckMate-026 was negative, it gave physicians greater insight into the application of tumor mutational burden (TMB), said Villaruz, an application that was later utilized in the CheckMate-227 trial.

Results of a subgroup from the CheckMate-227 trial, which were presented at the 2018 ASCO Annual Meeting, showed that the combination of nivolumab and low-dose ipilimumab (Yervoy) reduced the risk of progression or death by 52% versus standard platinum doublet chemotherapy for patients with metastatic PD-L1–negative, TMB-high NSCLC.3

In an interview at the 2018 OncLive® State of the Science Summit™ on Lung Cancer, Villaruz, assistant professor of medicine, Division of Hematology/Oncology, University of Pittsburgh, addressed the immunotherapy clinical trials that have informed the treatment of patients with NSCLC and the current state of biomarkers in the field.

OncLive: What do we know about immunotherapy in NSCLC?

Villaruz: I covered some of the data in the second-line setting, which established single-agent immunotherapy as part of the standard of care. I focused on the KEYNOTE-024 data, which established pembrolizumab in the first-line setting for PD-L1–overexpressing tumors.

It was truly practice changing. It was very impactful, and it established PD-L1 testing as part of the standard workup of advanced NSCLC.

I also spoke about the recently presented KEYNOTE-042 data, which looked at first-line pembrolizumab in patients with any level of PD-L1 expression. I mentioned some of the caveats in interpreting that data. I spoke about the CheckMate-026 data, which was a very similar trial to KEYNOTE-042, but with nivolumab as opposed to pembrolizumab. That trial is still very important even though it was negative, because it gives us insight into the TMB story as a biomarker for response to immune checkpoint inhibition.


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