Dr Borghaei on Determining Treatments Utilizing Biomarker Testing in NSCLC

Hossein Borghaei, DO, MS, chief, Division of Thoracic Medical Oncology, professor, Department of Hematology/Oncology, co-director, Immune Monitoring Facility, Gloria and Edmund M. Dunn chair, Thoracic Oncology, Fox Chase Cancer Center at Temple Health, discusses the importance of determining the most suitable treatment for patients with non–small cell lung cancer (NSCLC) through the use of biomarker testing.

The effective management of metastatic NSCLC hinges on acquiring various biomarkers to tailor treatment for patients, Borghaei begins. Among these biomarkers are genomic alterations, obtained through either DNA or RNA sequencing, he states. Another critical biomarker is PD-L1. In cases where tumors lack PD-L1 expression or do not exhibit a molecular alteration, questions arise regarding the most suitable treatment, Borghaei explains.

Furthermore, if a targetable lesion is present, targeted therapies can prove effective, he says. For tumors lacking PD-L1 expression, a combination of chemotherapy and immunotherapy has been the predominant treatment approach, Borghaei expands. This is based on numerous published results from randomized phase 3 trials that indicate the efficacy of combining a checkpoint inhibitor with chemotherapy in patients with this tumor profile, he emphasizes. Several studies also indicate the effectiveness of immunotherapy alone, without chemotherapy, Borghaei says.

Although the phase 3 CheckMate 227 trial (NCT02477826) of nivolumab (Opdivo) with or without ipilimumab (Yervoy) and platinum-doublet chemotherapy in patients with stage IV NSCLC incorporated patients with PD-L1–negative tumors, they were not part of the primary analysis groups, making statistical justification challenging, he continues. However, the phase 3 POSEIDON study (NCT03164616), which combined chemotherapy with tremelimumab (Imjudo) and durvalumab (Imfinzi) in patients with metastatic NSCLC, demonstrated clinical efficacy with the combination. Notably, in tumors lacking PD-L1 expression, the addition of a CTLA-4–directed antibody seemed to enhance the clinical efficacy of the combination, he explains.

The phase 3 CheckMate 9LA study (NCT03215706) adopted a comparable investigational treatment approach of 2 cycles of chemotherapy alongside ipilimumab and nivolumab, Borghaei states. Preliminary overall survival data indicate that PD-L1–negative tumors may benefit from this combination. The challenge lies in the absence of randomized phase 3 trials to provide clear guidance, he says. However, subgroup analyses from various studies indicate that a combination of a CTLA-4 antibody with a checkpoint inhibitor, with or without chemotherapy, could be a valuable consideration, Borghaei concludes.