Biagio Ricciuti, MD, Looks Toward Future Research in NSCLC Involving PD-L1 Expression

Biagio Ricciuti, MD, spoke about future analyses and major takeaways of a study analyzing outcomes with frontline immunotherapy based on PD-L1 expression in patients with non–small cell lung cancer.

At the 2022 American Society of Clinical Oncology Annual Meeting, CancerNetwork® spoke with Biagio Ricciuti, MD, of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, about future research into efficacy of pembrolizumab (Keytruda) monotherapy in patients with non–small cell lung cancer (NSCLC) who have PD-L1 tumor proportion scores (TPS) of 90% or more. At the conference, he and his fellow authors presented data from a study which looked at prolonged benefit of the agent at 3 years for patients with a high PD-L1 expression of 90% or more.

At the median follow-up of 42.6 months, treatment benefit included a median progression-free survival of 5.1 months and median overall survival of 19.0 months in all patients with PD-L1 expression above 50%. For patients who had PD-L1 TPS of 90% or more, median PFS was 6.0 months vs 4.5 months with PD-L1 TPS of 50% to 89% (HR, 0.67; P <.001). Corresponding median OS was 30.2 months vs 16.9 months (HR, 0.66; P <.01).


We now are in the phase of gathering additional data, and we did some more qualitative analyses. Specifically, we will try to enlarge the cohort of [patients with] NSCLC who will be profiled with multiplex immunofluorescence so that we can validate our findings. We also were planning to include more samples for [genomic] profiling so that we can validate the mutations that are found in high vs very high PD-L1 expressors. As part of the study, we will also try to explore whether there are any differences in safety between the 2 groups. There are other scientists that are currently working on this.

The most important takeaway from this analysis is that among patients with NSCLC and PD-L1 expression of 50% or greater who have highly altered genes, we shouldn’t consider this patient population as a single group of patients but [rather as a] more heterogeneous group with different immunophenotypic features which may depend on the PD-L1 expression. In addition to this, important data [reveal] that patients with very high expression at 3 years kept experiencing prolonged benefits from immunotherapy. These patients are more likely to complete the treatment cycles of anti–PD-1 monotherapy [to 2 years]. Because of this, we may individualize treatment based on very high PD-L1 expression when we have to decide whether we want to prescribe a first-line [treatment], which is a monotherapy vs a chemoimmunotherapy combination. In this setting, this information might be helpful to guide through the transition.


Ricciuti B, Elkrief A, Alessi J, et al. Three-year outcomes and correlative analyses in patients with non–small cell lung cancer (NSCLC) and a very high PD-L1 tumor proportion score (TPS) ≥ 90% treated with first-line pembrolizumab. J Clin Oncol. 2022;40(suppl 16):9043. doi: 10.1200/JCO.2022.40.16_suppl.9043