High-Dose Hyperfractionated Radiotherapy Improves PFS, OS in LS-SCLC

High-dose hyperfractionated thoracic radiotherapy can improve outcomes over standard first-line radiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC), according to phase 3 trial results presented at the 2023 ASTRO Annual Meeting.

Patients who received high-dose hyperfractionated radiotherapy along with chemotherapy had significant improvements in progression-free survival (PFS) and overall survival (OS), when compared to patients who received standard radiotherapy and chemotherapy, according to study presenter Jiayi Yu, PhD, of Peking University Cancer Hospital & Institute in Beijing.

However, a discussant for this study questioned whether these results are generalizable to a broader group of patients with LS-SCLC.

This phase 3 trial (ClinicalTrials.gov Identifier: NCT03214003) was conducted in China. It was designed to compare high-dose, twice-daily thoracic volumetric modulated arc radiotherapy (VMAT) to standard-dose VMAT as first-line treatment for LS-SCLC.

A total of 224 patients were randomly assigned to radiotherapy — 108 to receive 54 Gy in 30 fractions and 116 to receive 45 Gy in 30 fractions. All patients also received chemotherapy, which consisted of etoposide and cisplatin or carboplatin.

Baseline characteristics were well balanced between the treatment arms. Patients were 18 to 70 years of age and had ECOG performance status scores of 0 or 1. The median follow-up was 45 months.

The median OS was 62.4 months in the hyperfractionated radiotherapy arm and 43.1 months in the standard radiotherapy arm (hazard ratio [HR], 0.59; 95% CI, 0.42-094; P =.001). The 2-year OS rate was 77.7% and 53.4%, respectively.

The median PFS was 30.5 months in the hyperfractionated arm and 16.7 months in the standard arm (HR, 0.77; 95% CI, 0.54-1.10; P =.044).

Adverse events (AEs) were similar between the treatment arms, Dr Yu said. The grade 3-4 AEs related to radiotherapy were esophagitis (12.9% in the hyperfractionated arm and 12.1% in the standard arm) and pneumonitis (4.6% and 6%, respectively). There was 1 fatal AE (myocardial infarction) in the hyperfractionated arm and none in the standard arm.

Based on these results, Dr Yu concluded that high-dose hyperfractionated thoracic radiotherapy plus chemotherapy is an alternative treatment option for LS-SCLC. 

However, a study discussant raised questions about these findings and their generalizability.

“This is a carefully selected patient population that is not representative of most patients with limited-stage small cell lung cancer,” said the discussant, Kristin Higgins, MD, from Winship Cancer Institute of Emory University in Atlanta.

Dr Higgins noted that patients were 70 years of age or younger, around 60% of patients in each arm had an ECOG performance status score of 0, and nearly 40% of patients in each arm were never smokers.  

Dr Higgins also pointed out that the rate of high-grade esophagitis was “quite low” in both arms, when compared to rates seen in other phase 3 trials. “[I]t certainly is puzzling that we aren’t seeing more esophagitis with this dose escalation,” she said.

Disclosures: The study authors reported having no relevant disclosures. Dr Higgins disclosed relationships with AstraZeneca, Jazz Pharmaceuticals, Regeneron, Janssen Pharmaceuticals, and Picture Health.

Reference

Yu J, Jiang L, Zhao L, et al. High dose hyperfractionated thoracic radiotherapy vs standard dose for limited stage small-cell lung cancer: A multicentre, open-label, randomized, phase 3 trial. Presented at ASTRO 2023. September 30-October 4, 2023. Abstract 1.

This article originally appeared on Cancer Therapy Advisor