Evaluating the Safety of Immunotherapy in NSCLC Patients With Comorbidities

Combination immunotherapy with nivolumab plus ipilimumab is safe as a first-line therapy for patients with advanced non–small-cell lung cancer (NSCLC) and comorbidities such as brain metastases, kidney or renal disease, and HIV, according to the results of the phase III CheckMate 817 trial. Findings were presented on September 8, 2019, at the International Association for the Study of Lung Cancer (IASLC) 2019 World Conference on Lung Cancer (WCLC) in Barcelona.

“For those patients with ECOG [Eastern Cooperative Oncology Group] performance status 2, this regimen is as safe as it is for the general population. The treatment-related adverse events (TRAEs) leading to treatment discontinuation were also comparable, and treatment-related deaths were very low in both cohorts,” said study presenter Fabrice Barlesi, MD, PhD, of Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France. According to Barlesi, the safety profile demonstrated in the current study is in line with data from previous research.

Little data exists on the safety and efficacy of immunotherapy in patients with NSCLC and serious comorbidities. In the current single-arm, non-randomized trial, Barlesi and colleagues studied the safety of nivolumab, a programmed death 1 immune checkpoint inhibitor, in combination with ipilimumab, a monoclonal antibody that targets CTLA-4. Patients had either newly diagnosed stage IV or recurrent NSCLC.

A total of two experimental groups with untreated advanced NSCLC were tested. In Cohort A1, patients (n = 198) had either impaired or good performance status plus comorbidities. Specifically, this group consisted of: 1) patients with an ECOG score of PS 2 or 2) patients with an ECOG score of PS 0–1, as well as asymptomatic untreated brain metastases, HIV, hepatic disease, or renal disease. In Cohort A (n = 391), patients were healthier and exhibited an ECOG score of PS 0–1. Patients who harbored EGFR mutations or ALK translocations sensitive to available targeted therapy were excluded.

According to Barlesi, patients with “ECOG 2 are usually excluded from registration trials, and we have very [little] information for these patients.”

For 2 years, patients were given a 240-mg flat dose of nivolumab every 2 weeks along with low-dose ipliumumab (1 mg/kg) every 6 weeks. Primary outcomes included the frequency of grade 3 to 5 TRAEs and immune-mediated adverse events. Secondary outcomes included survival and response measures.

In Cohort A, 77% of patients exhibited a TRAE of any grade, and 35% exhibited grade 3 to 4 TRAEs. In Cohort A1, 67% of patients experienced any TRAE, and 28% experienced grade 3 to 4 TRAEs. Specifically, in those with an ECOG score of 2, these measures were 63% and 26%, respectively.

With respect to secondary endpoints, the overall response rate in Cohort A1 was 24%: 19% in patients with an ECOG score of PS 2, and 37% for patients with an ECOG score of PS 0–1 and comorbidities.

“Very excitingly, the 1-year duration of response in this specific population [Cohort A1] was 57%, which is really appreciable,” said Barlesi. On a related note, progression-free survival (PFS) was longer in cohort A compared with cohort A1.

Barlesi et al also examined the effects of biomarkers in Cohort A1. Patients with programmed death ligand 1 expression greater than 50% exhibited a PFS of 9.6 months, and those with tumor mutational burden of more than 10 megabases exhibited a PFS of 8.3 months. Patients with these specific biomarkers exhibited the longest PFS in the study.

When asked whether special patient populations-including those with ECOG PS 2-should be included in clinical trials, Barlesi said, “I think that we should try to perform specific studies for this population, at least at the beginning of the development of new drugs or strategies.”