TOPLINE:

Patients with extensive-stage small cell lung cancer (SCLC) receiving immunochemotherapy before 3:00 PM showed significantly longer overall survival of 18.4 months vs 11.6 months for later administration. Early administration was associated with improved progression-free survival of 7.6 months vs 5.8 months for later treatment.

METHODOLOGY:

• A meta-analysis revealed that patients receiving single-agent immune checkpoint inhibitor infusions primarily in the morning or early afternoon showed nearly double the overall survival and progression-free survival compared with later administration. Investigations on infusion timing have predominantly focused on non-small cell lung cancer.
• Researchers conducted a retrospective analysis of 397 patients with extensive-stage SCLC who received first-line anti-PD-L1 plus chemotherapy between May 2019 and October 2023 at Hunan Cancer Hospital.
• Analysis focused on median infusion time during the first four immunochemotherapy cycles, with time of day of administration calculated across multiple thresholds from 11:00 AM to 4:30 PM.
• Participants received atezolizumab (1200 mg per course) or durvalumab (1500 mg per course) intravenously over 30 minutes, followed by standard chemotherapy regimens including etoposide (80-100 mg/m²) on days 1-3 and carboplatin or cisplatin on day 1.
• Propensity score matching (1:2) was applied to balance baseline characteristics between early and late administration groups, with progression-free survival as the primary endpoint, and overall survival was a secondary endpoint.

TAKEAWAY:

• Optimal time of day administration cutoff was identified at 3:00 PM, with patients receiving treatment before this time demonstrating significantly improved progression-free survival (adjusted hazard ratio [AHR], 0.483; 95% CI, 0.357-0.654) and overall survival (AHR, 0.373; 95% CI, 0.265-0.526).
• The early administration group showed a higher objective response rate than those receiving treatment later (82.3% vs 67.9%; P = .017) in the entire cohort, with similar benefits observed in a matched subset (85.8% vs 67.9%; P = .011).
• Multivariable analysis confirmed early administration as an independent favorable prognostic factor, while baseline liver and brain metastases were identified as poor prognostic indicators.
• Subgroup analyses revealed the most pronounced survival benefits in male patients, those with a smoking history, and patients without liver metastases.

IN PRACTICE:

“This study provides real-world evidence supporting the survival benefit of earlier immunochemotherapy administration in patients with ES-SCLC. These findings add to the growing body of knowledge on the clinical relevance of circadian timing in cancer treatment,” wrote the authors of the study.

SOURCE:

The study was led by Zhe Huang, MD, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. It was published online in Cancer.

LIMITATIONS:

According to the authors, the study had several limitations, including the retrospective nature of the analysis and the relatively small number of patients who received treatment after 3:00 PM, which reduced statistical power for late-infusion analyses. Additionally, because all patients received combination immunochemotherapy, isolating the independent effects of chemotherapy from immunotherapy was challenging. The predominance of male patients (approximately 90%) in the study population may limit the generalizability of findings across genders.

DISCLOSURES:

The study received financial support through grants from the National Natural Science Foundation of China (grant numbers: 82222048, 82003206, 82173338, and 82102747). The funding agencies had no role in the study design, data collection, analysis, interpretation, manuscript writing, or the decision to submit the article for publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.