Biagio Ricciuti, MD, Reviews Combination Immunotherapy Regimens in NSCLC

Biagio Ricciuti, MD, spoke about combination immunotherapy regimens for patients with non–small cell lung cancer who did not respond well to prior treatment.

CancerNetwork® spoke with Biagio Ricciuti, MD, of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute at the 2022 American Society of Clinical Oncology Annual Meeting, to discuss regimens of combination immunotherapy for patients with non–small cell lung cancer (NSCLC) who did not respond to prior treatment. Ricciuti spoke about which combinations looked most promising and how currently available data can inform treatment decisions.

At the conference, Ricciuti and colleagues presented data from a study of patients with NSCLC who were treated with frontline pembrolizumab (Keytruda) correlating long-term outcomes with high (≥50%) vs very-high (≥90%) PD-L1 expression.


There are several combination therapies that are now being investigated in different settings. We have different combination therapies for instance, targeted therapies such as tyrosine kinase inhibitors and immunotherapy among patients with NSCLC. [There are also] combination therapies of different immune checkpoint inhibitors, such as antibodies against TIGIT in combination with PD-1 blockade as well as chemotherapy-based regimens plus immunotherapy. The landscape is expanding. The reason why this study is helpful is to inform trial design and interpretation, but also because high PD-L1 expression levels [are not typically included as] stratification or randomization factors in clinical trials.

We can imagine that if the 2 arms are imbalanced in terms of PD-L1 expression in any clinical trials of immunotherapies, then the results may be affected as well. We need to make sure that the treatment arms are well balanced with very high vs high PD-L1 expression. We have multiple immunotherapies that have been approved in first-line setting. For instance, we have an approval for an anti–PD-1 monotherapy in patients with PD-L1 TPS of 1% of greater or we have chemotherapy and immunotherapy approved for all [patients] with NSCLC regardless of PD-L1 expression. We are in a situation where we have to choose between different treatment approaches. Our studies suggest that PD-L1 expression may inform which treatment we use because if patients with very high PD-L1 expressions derive such a benefit from monotherapies, we may think about sparing the toxicity of chemotherapy in that patient population. Therefore, we feel that the study [of patients with NSCLC with PD-L1 and a tumor proportion score of 90% or more] may help inform clinical trials and treatment decisions. We have ongoing prospective trials to determine whether chemotherapy and immunotherapy vs immunotherapy are similar or different in terms of clinical outcomes, but we’ll still need to see those results. In the meantime, we can try to leverage retrospective data to inform treatment decisions.


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