TOPLINE:

Weight-based pembrolizumab dosing demonstrated comparable effectiveness and safety to fixed dosing in patients with advanced non-small cell lung cancer (NSCLC). In a real-world cohort of 414 patients, the median overall survival (OS) was 23.26 months vs 18.43 months with weight-based dosing vs fixed dosing, and rates of laboratory-defined immune-related adverse events (irAEs) were similar between groups.

METHODOLOGY:

• Pembrolizumab is commonly administered as a fixed 200-mg dose every 3 weeks in advanced NSCLC. Although pharmacokinetic modeling supports both fixed-dose and weight-based strategies, concerns about potential overdosing in populations with lower body weight and cost implications of fixed dosing prevail. Additionally, real-world evidence comparing the effectiveness and safety of fixed vs weight-based pembrolizumab dosing in patients with NSCLC remains limited.
• To address this, researchers conducted a retrospective cohort study of 414 patients newly diagnosed with metastatic or unresectable NSCLC (median age at diagnosis, 67 years) between 2016 and 2021 who received pembrolizumab either as a fixed dose (200 mg once every 3 weeks; n = 339) or a weight-based dose (2 mg/kg once every 3 weeks; n = 75).
• The primary endpoint was OS, and other outcomes included irAEs. The median follow-up duration was 42.0 months for the overall cohort, 43.2 months for the fixed-dose group, and 26.9 months for the weight-based dosing group.
• Researchers used inverse probability of treatment weighting to balance baseline covariates and assessed the noninferiority of fixed-dose vs weight-based pembrolizumab dosing using a prespecified hazard ratio (HR) margin of 1.20.
• In the entire cohort, 52.4% vs 47.6% received immune checkpoint inhibitor (ICI) monotherapy vs ICIs plus platinum chemotherapy; combination therapy was used more often in the weight-based dosing group than in the fixed-dose group (64.0% vs 44.2%; P = .03).

TAKEAWAY:

• Overall, the median OS was similar between the fixed- and weight-based pembrolizumab dosing cohorts (18.43 vs 23.26 months; HR, 0.73; P = .11), and after applying inverse probability of treatment weighting, weight-based dosing met the prespecified noninferiority criterion.
• The incidence of irAEs of grade 2 or higher did not differ significantly between groups, and the median OS was comparable among patients who developed irAEs of grade 2 or higher (fixed-dose vs weight-based dosing cohorts: 20.86 vs 22.93 months; HR, 0.86; P = .43) as well as among those who developed irAEs of grade 1 or lower or no toxicity.
• In a subgroup analysis stratified by treatment regimen, no differences in OS were observed between dosing strategies for patients who received ICI monotherapy (HR, 0.61) or ICI-platinum doublet therapy (HR, 0.67); no overall differences in the median OS were detected across age, BMI, smoking status, PD-L1 tumor proportion score, or the neutrophil-to-lymphocyte ratio (P ≥ .05).
• In multivariable analyses, the Eastern Cooperative Oncology Group (ECOG) performance status and number of treatment cycles were independently associated with survival; patients with ECOG performance status 2 had more than a twofold higher risk for death than those with ECOG performance status 0 (HR, 2.12; P < .001), and each additional treatment cycle reduced the risk for death by 9% (HR, 0.91; P < .001).
• Among patients who received weight-based dosing, OS was similar when comparing upper vs lower tertiles for BMI (30.16 vs 21.06 months; HR, 0.78; P = .24) and upper vs lower tertiles for weight (23.26 vs 21.06 months; HR, 1.01; P = .96).

IN PRACTICE:

“In conclusion, while fixed dosing offers administrative simplicity, our findings demonstrate that weight-based pembrolizumab dosing is equally effective and safe and more cost-efficient and may reduce toxicity in underweight patients,” the study authors wrote. “Incorporating this approach may expand access to life-saving treatment, particularly in resource-limited settings where fixed-dose ICI treatment remains unattainable.”

SOURCE:

The study, led by Eliya Shachar, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, was published online in JCO Oncology Practice.

LIMITATIONS:

The study was limited by its retrospective design. Treatment groups were unbalanced in size, and baseline heterogeneity could have affected outcomes. Shorter follow-up limited the ability to evaluate long‑term survival. The safety analysis was confined to laboratory adverse events and did not capture the full spectrum of clinically diagnosed irAEs. Additionally, progression-free survival and detailed postprogression therapies were not consistently available and could not be reliably analyzed.

DISCLOSURES:

The authors did not disclose any funding information. One author disclosed receiving support in part from T32 National Institutes of Health funding for the Patient-Centered Outcomes Research Training in Urologic and Gynecologic Cancers. Another author declared receiving speaker fees from Merck Sharp & Dohme (MSD) Oncology, AstraZeneca, Takeda, Roche, and BMS, as well as research funding from MSD Oncology and Roche. No other potential conflicts of interest were reported by the authors.

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