Simultaneous Integrated Boost vs. Routine IMRT in Limited-Stage Small-Cell Lung Cancer: An Open-Label, Non-Inferiority, Randomized, Phase 3 Trial—Interim Analysis

Purpose/Objective(s)

Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.

Materials/Methods

This randomized, non-inferiority, open-label, phase 3 study was done in a single institution in China. Patients aged 18–70 years who was diagnosed with treatment-naïve and confirmed limited-stage SCLC were eligible. All participants received 4-6 courses of intravenous cisplatin 75 mg/m² or carboplatin (area under the curve 5–6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m² on days 1–3 every 3 weeks. Participants were randomly assigned (1:1) stratifying for the timing of thoracic radiation therapy to receive simultaneous integrated boost radiotherapy (PGTV 60.2Gy/2.15Gy/28F, PTV 50.4Gy/1.8Gy/28F) or conventional fractionated radiotherapy (PTV 60Gy/2Gy/30F) to the primary lung tumor and CT positive lymph node metastases. Responders were offered prophylactic cranial irradiation of 25Gy/2.5Gy/10F.The primary endpoint was 2-year progression-free survival, the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.

Results

Between February 2017, and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among which 106 patients in the conventional fractionated radiotherapy group,110 patients in the SIB group. The 2-year progression-free survival rates were 45.2% vs 38.3% and the median progression-free survival was 18 months (95%CI:9.06-26.39) in the conventional fractionated radiotherapy group versus 17 months(95%CI:11.47-22.53) in the SIB group (P=0.2, HR 1.22,95%CI:0.87-1.72). The 2-year overall survival rates were 73.5% VS 60.9% (P=0.14, HR 1.35,95%CI:0.90-2.04). The 2-year local-regional recurrence-free survival rates were 68.7% VS 69.9% (P = 1.0, HR = 0.98, 95% CI = 0.62-1.56). The most common grade 3–4 adverse events were myelosuppression (21.7% vs 15.4%, P = 0.83), radiation pneumonitis (4.7% vs 2.7%, P = 0.44), radiation esophagitis (3.8% vs 1.8%, P = 0.51).

Conclusion

Simultaneous integrated boost radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with limited-stage small cell lung cancer. Further enrollment and follow-up are warranted to confirm these findings in this ongoing trial. This trial is registered at ClinicalTrials.gov, NCT04500145.