Hypofractionated Radiotherapy followed by Hypofractionated Boost with weekly concurrent chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Results of A Prospective Phase II Study (GASTO-1049)

Abstract

Purpose: We launched a prospective phase 2 clinical trial to explore the safety and efficacy of hypofractionated radiation therapy (hypo-RT) followed by hypofractionated boost (hypo-boost) combined with concurrent weekly chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC).

Methods and materials: Patients with newly diagnosed LA-NSCLC with unresectable stage III disease were recruited between June 2018 and June 2020. Patients were treated with hypo-RT (40 Gy in 10 fractions) followed by hypo-boost (24-28 Gy in 6-7 fractions) combined with concurrent weekly chemotherapy (docetaxel 25 mg/m² and nedaplatin 25 mg/m²). The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), objective response rate (ORR), and toxicities.

Results: From June 2018 to June 2020, 75 patients were enrolled with a median follow-up duration of 28.0 months. The ORR of the whole cohort was 94.7%. Disease progression or death was recorded in 44 (58.7%) patients, with a median PFS of 21.6 months (95% confidence interval [CI], 15.6-27.6 months). The 1- and 2-year PFS rates were 81.3% (95% CI, 72.5%-90.1%) and 43.3% (95% CI, 31.5%-55.1%), respectively. The median OS, DMFS, and LRFS had not been reached at the time of the last follow-up. The 1- and 2-year OS rates were 94.7% (95% CI, 89.6%-99.8%) and 72.4% (95% CI, 62.0%-82.8%), respectively. The most frequent acute nonhematologic toxicity was radiation esophagitis. Grade (G) 2 and G3 acute radiation esophagitis were observed in 20 (26.7%) and 4 (5.3%) patients, respectively. Thirteen patients (13/75, 17.3%) had G2 pneumonitis and no G3-G5 acute pneumonitis occurred during follow-up.

Conclusions: Hypo-RT followed by hypo-boost combined with concurrent weekly chemotherapy could yield satisfactory local control and survival outcomes with moderate radiation-induced toxicity in patients with LA-NSCLC. The new potent hypo-CCRT regimen significantly shortened treatment time and provided the potential opportunity for the combination of consolidative immunotherapy.

Trial registration: ClinicalTrials.gov NCT03900117.