Naiyer Rizvi, MD

“In CheckMate 227, the benefit of nivolumab [Opdivo] plus ipilimumab [Yervoy] was the same in tumor mutational burden–high patients whether or not they were programmed cell death ligand 1 (PD-L1)–high or –low,” said formal discussant of this paper, Naiyer Rizvi, MD, Director of Thoracic Oncology and Director of Immunotherapeutics in the Division of Hematology/Oncology at Columbia University Medical Center, New York.

“We have to view these results in the context of other trials. This trial is a tumor mutational burden–selected population, and this is different from KEYNOTE-024. Only 58% of patients enrolled in CheckMate 227 had tissue available for tumor evaluation,” Dr. Rizvi told the audience. 

“The toxicity is greater with the immunotherapy combination. Seventeen percent discontinued treatment due to treatment-related adverse events. Tumor mutational burden–selected patients will be on therapy longer, so we will need longer follow-up to determine if there will be more discontinuations,” he noted. 

Clinical Implications

Dr. Rizvi provided some guidance as to how to integrate tumor mutational burden–high and tumor mutational burden–low into decision-making, along with PD-L1–high and PD-L1–low. For tumor mutational burden–high patients, in those who are PD-L1–high, pembrolizumab (Keytruda) or nivolumab plus ipilimumab are effective options; in PD-L1–low non–small cell lung cancer (NSCLC), nivolumab plus ipilimumab should be used. For tumor mutational burden–low patients, in those who are PD-L1–high, pembrolizumab is a possibility and chemotherapy can be used; in PD-L1–low patients, chemotherapy should be used. 

“We need tumor mutational burden data from the immunotherapy plus chemotherapy combination trials,” noted Dr. Rizvi.

“Tumor mutational burden should be a standard biomarker for initial evaluation of NSCLC. PD-L1 remains a standard of care and should be used in concert with tumor mutational burden,” Dr. Rizvi said. “Tumor mutational burden has a potential impact beyond NSCLC and has a potential pan-cancer application. This marker can identify patients for adjuvant, neoadjuvant, or consolidation therapy. Also, there is the potential for blood-based tumor mutational burden.” ■

DISCLOSURE: Dr. Rizvi reported no conflicts of interest.