Association of extended dosing intervals or delays in pembrolizumab-based regimens with survival outcomes in advanced non-small cell lung cancer

Sehgal, Kartik; Bulumulle, Anushi; Brody, Heather; Gill, Ritu R.; Macherla, Shravanti; Qilleri, Aleksandra; McDonald, Danielle C.; Cherry, Cynthia R.; Shea, Meghan; Huberman, Mark S.; VanderLaan, Paul A.; Weiss, Glen J.; Walker, Paul R.; Costa, Daniel B.; Rangachari, Deepa

BACKGROUND: Besides modeling/simulation-based analysis, no post-approval studies have evaluated optimal administration frequency of pembrolizumab in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We performed a multicenter retrospective cohort study to evaluate association between survival outcomes and treatment extensions/delays of pembrolizumab-based regimens in advanced NSCLC patients. Those who had received at least four cycles in routine practice were divided into two groups: non-standard (Non-Std: ≥2 cycles at intervals >3weeks +3days) and standard (Std: all cycles every 3weeks or 1 cycle >3weeks +3days). RESULTS: Among 150 patients, 92 (61%) were eligible for the study (Non-Std:27, Std:65). Reasons for patients with extensions/delays in the Non-Std group included: immune-related adverse events (irAEs,33%), non-irAE-related medical issues (26%), and patient-physician preference (41%). Non-Std group was more likely to have higher PD-L1 tumor proportion score, higher number of treatment cycles and pembrolizumab monotherapy. Univariate and 6-month landmark analyses showed longer median overall survival (OS) and progression-free survival (PFS) in Non-Std group compared to the Std group. After multivariable adjustment for confounding factors, there was no significant difference in OS [HR 1.2 (95%C.I.: 0.3–4.8), p=0.824] or PFS [HR 2.6 (95%C.I.: 0.7–9.6), p=0.157] between the two groups. CONCLUSION: Our study shows that a significant proportion of advanced NSCLC patients receive pembrolizumab-based regimens with extended intervals or delays in routine clinical practice and with similar outcomes to those receiving treatment at label-specified 3-week intervals. Given the durability of benefit seen and the potential for cost reduction and decreased infusion frequency in these patients, this requires validation in prospective trials.