European Trial Indicates No Additional Benefit From Preoperative Radiotherapy Following Neoadjuvant Chemotherapy in Stage IIIA/N2 NSCLC
In a phase III trial reported in The Lancet, Pless et al in the Swiss Group for Clinical Cancer Research found that adding preoperative radiation following neoadjuvant chemotherapy did not appear to improve outcomes vs neoadjuvant chemotherapy alone in patients with stage IIIA/N2 non–small cell lung cancer (NSCLC).
Study Details
In the trial, 232 patients from 23 sites in Switzerland, Germany, and Serbia were randomly assigned between 2001 and 2012 to receive 3 cycles of neoadjuvant chemotherapy with 100 mg/m² of cisplatin and 85 mg/m² of docetaxel followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks (n = 117) or neoadjuvant chemotherapy alone (n = 115). Randomization was stratified by center, mediastinal bulk, and weight loss. The primary endpoint was event-free survival in the intent-to-treat population.
Event-Free and Overall Survival
The median follow-up was 52 months. Median event-free survival was 12.8 months (95% confidence interval [CI] = 9.7–22.9 months) in the chemoradiotherapy group and 11.6 months (CI = 8.4–15.2 months) in the chemotherapy group (hazard ratio [HR] = 1.1, P = .67). There was also no significant difference on per-protocol analysis (22.0 vs 15.4 months, HR = 1.1, P = .59).
Median overall survival was 37.1 months (95% CI = 22.6–50.0 months) vs 26.2 months (19.9–52.1 months; HR = 1.0, 95% CI = 0.7–1.4). There was no difference on per-protocol analysis (49.5 vs 33.5 months, HR = 1.1).
Objective response occurred in 51% (P = .240) of patients after chemotherapy and 61% (P = .012) after radiotherapy (including complete response in 3%) in the chemoradiation group and 44% in the chemotherapy group. R0 resection was achieved in 91% vs 81%.
Adverse Events
Chemotherapy-related adverse events occurred in most patients, but 91% of patients overall completed 3 cycles. Grade 3 radiotherapy-related adverse events consisted of dysphagia (7%), fatigue (1%), and neurotoxicity (1%). Three patients in the chemotherapy group died within 30 days after surgery.
The investigators concluded: “Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer.”
Miklos Pless, MD, of Kantonsspital Winterthur, Switzerland, is the corresponding author of The Lancet article.
The study was funded by the Swiss State Secretariat for Education, Research, and Innovation; Swiss Cancer League; and Sanofi. Dr. Pless and Arnaud Roth, MD, have served as advisory board members for Sanofi.
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